CN117597446A

CN117597446A - 非自然发生的5’-非转译区及3’-非转译区及其用途

Info

Publication number: CN117597446A
Application number: CN202280045320.1A
Authority: CN
Inventors: 韩承洙; 朴多炫; 吴宜林; 许容豪; 李珍奉; 董主荣; 申胜显; 林昌奎
Original assignee: Hanmi Pharmaceutical Co Ltd
Current assignee: Hanmi Pharmaceutical Co Ltd
Priority date: 2021-06-24
Filing date: 2022-06-24
Publication date: 2024-02-23

Abstract

分离的多核苷酸，其包含编码非自然发生的5’‑非转译区的核苷酸序列及编码非自然发生或自然发生的3’‑非转译区的核苷酸序列。因此，所述多核苷酸增加了mRNA稳定性和转译效率，因此可用于有效获得所需的多胜肽。

Description

非自然发生的5’-非转译区及3’-非转译区及其用途

技术领域

本揭示涉及非自然发生的5’-非转译区及3’-非转译区及其用途。

背景技术

核酸疫苗使用由DNA或RNA编码的抗原。DNA疫苗一般而言包括插入细菌质体的抗原编码基因，其由真核启动子调节。另一方面，RNA疫苗使用讯息RNA(mRNA)或其他抗原编码的RNA。类似于蛋白疫苗，核酸疫苗可经由各种途径递输，例如肌肉、皮下、粘膜或经皮途径。

DNA疫苗已知诱发出比胜肽疫苗、细胞疫苗、病毒载体疫苗及RNA疫苗更弱的免疫反应。除了具有低免疫原性之外，DNA疫苗可能被插入宿主基因体中以诱发肿瘤形成。因此，需要基于RNA的疫苗。

发明内容

技术挑战

一实施例提供一分离的多核苷酸，其包括编码非自然发生的5’-非转译区(5’-UTR)的核苷酸序列、编码3’-非转译区(3’-UTR)的核苷酸序列或其组合。

另一实施例提供RNA，其可通过使用第一实施例的多核苷酸作为模板转录而获得。

另一实施例提供一分离的多核苷酸，其包括非自然发生的5’-非转译区(5’-UTR)核苷酸序列、3’-非转译区(3’-UTR)核苷酸序列或其组合。

另一实施例提供一获得RNA的方法，其包括以多核苷酸作为模板将RNA转录。

另一实施例提供一获得多胜肽的方法，其包括将通过上述方法获得的RNA转译。

另一实施例提供一组合物，其包括递输多核苷酸至受试者的多核苷酸。

另一实施例提供一组合物，其包括诱发对多核苷酸的免疫反应的多核苷酸。

另一实施例提供一使用多核苷酸的方法，其包括将多核苷酸导入宿主细胞中。

解决问题的手段

如本文所用，用于与多胜肽或多核苷酸有关的术语“一致性”意指通过比较序列而确定至少两个多胜肽序列或多核苷酸序列之间的关系。一致性表示通过胺基酸残基列或核苷酸残基列之间的许多匹配而确定的序列相关性水平。相关的多胜肽或多核苷酸的一致性可通过已知的方法计算。当应用于多胜肽或多核苷酸时，术语“％一致性”定义为在将候选胺基酸序列或核苷酸序列与第二序列比对以获得最大百分比一致性之后，候选序列的残基与第二序列的残基一致的百分比，并在需要时导入间隙。用于比对的方法与程式为本领域中已知。所述程式可为，例如，BLAST、Smith-Waterman算法或Needleman-Wunsch算法。

如本文所用，“5’-非转译区(5’-UTR)”意指不编码多胜肽的mRNA区，直接在欲通过核醣体转译的mRNA转录本的第一个密码子的上游(亦即，5’)，亦即，起始密码子。

如本文所用，“3’-非转译区(3’-UTR)”意指不编码多胜肽的mRNA区，直接在mRNA转录本转译传讯终止的密码子的下游(亦即，3’)，亦即，终止密码子。

如本文所用，“开读框(ORF)”意指编码多胜肽的DNA的连续区，其始于起始密码子，例如，甲硫胺酸密码子(ATG)，并止于终止密码子，例如TAA、TAG或TGA。

如本文所用，“多腺苷酸序列”或“多(A)尾”意指在3’-UTR下游的包括多个连续单磷酸腺苷的mRNA区，例如，直接在3’-UTR下游(亦即，3’)。多(A)尾可包括10至300个单磷酸腺苷。举例而言，多(A)尾可包括10、20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、190、200、210、220、230、240、250、260、270、280、290或300个单磷酸腺苷。多(A)尾可包括，例如，50至250个单磷酸腺苷。活体(例如细胞或受试者)中的多(A)尾可用于保护mRNA免于酵素(例如，细胞质中的酵素)攻击，并有助于终止转录、从细胞核输出mRNA及转译。

如本文所用，术语“可操作地连接”意指在单一核酸片段上连接各核苷酸序列，使得一功能受另一者的影响。举例而言，当启动子能影响编码序列的表达时(亦即，当通过启动子调节编码序列的转录时)，启动子可操作地连接至编码序列(例如，ORF)。编码序列可以正义或反义方向可操作地连接至调节序列。

如本文所用，除非另有指明核苷酸序列的位置，否则核苷酸序列从5’端连接至3’端或位于5’端至3’端。

如本文所用，术语“载体”或“核酸构筑体”意指可携带基因、ORF或DNA片段进入细胞的任意核酸。载体可为，例如，可在细胞中复制的载体。载体可为病毒、噬菌体、原病毒、质体、噬菌体载体(phagemid)、转位子或人工染色体，例如酵母人工染色体(YAC)、细菌人工染色体(BAC)或植物人工染色体(PLAC)。

第一实施例提供一分离的多核苷酸，其包括编码非自然发生的5’-非转译区(5’-UTR)的核苷酸序列、编码3’-非转译区(3’-UTR)的核苷酸序列或其组合。

分离的多核苷酸可包括编码非自然发生的5’-UTR的核苷酸序列及编码非自然发生的3’-UTR的核苷酸序列。分离的多核苷酸可包括编码非自然发生的5’-UTR的核苷酸序列及编码自然发生的3’-UTR的核苷酸序列。

分离的多核苷酸可为聚去氧核糖核苷酸。

5’-UTR可包括非自然发生的核苷酸序列。5’-UTR可与SEQ ID NO:1的核苷酸序列具有70％或以上，例如，80％或以上、90％或以上或95％或以上的序列一致性。5’-UTR可包括SEQ ID NO:1、2、3、4、5、6、7、8、9、10、11、12或其组合的序列。5’-UTR可为多核糖核苷酸。编码非自然发生的5’-非转译区(5’-UTR)的核苷酸序列可包括SEQ ID NO:22、23、24、25、26、27、28、29、30、31、32、33或其组合的序列。彼等序列可为聚去氧核糖核苷酸。

3’-UTR可包括非自然发生的或自然发生的核苷酸序列。3’-UTR可与SEQ ID NO:15的核苷酸序列具有70％或以上，例如，80％或以上、90％或以上或95％或以上的序列一致性，并可与SEQ ID NO:20的核苷酸序列具有70％或以上，例如，80％或以上、90％或以上或95％或以上的序列一致性。3’-UTR可包括SEQ ID NO:14、15、16、17、18、19、20或其组合的序列。编码非自然发生或自然发生的3’-非转译区(3’-UTR)的核苷酸序列可包括SEQ ID NO:34、35、36、37、38、39、40或其组合。

编码非自然发生的或自然发生的3’-非转译区(3’-UTR)的核苷酸序列可包括限制酶的识别位置。限制酶可包括XhoI、NheI、或XhoI及NheI。

编码5’-UTR的核苷酸序列可进一步包括可操作地连接至5’-UTR的上游启动子区的核苷酸序列。

编码5’-UTR的核苷酸序列可包括可转录核苷酸序列或用于导入可转录核苷酸序列的核苷酸序列，且可转录核苷酸序列或用于导入可转录核苷酸序列的核苷酸序列可能在编码5’-UTR的核苷酸的下游可操作地连接至5’-UTR。

可转录核苷酸序列可为编码多胜肽或RNA的序列。多胜肽可为抗原性多胜肽或治疗性多胜肽。抗原性多胜肽可为病毒抗原性多胜肽。病毒抗原性多胜肽可为至少一β冠状病毒(BetaCoV)抗原性多胜肽、至少一呼吸道融合病毒(RSV)抗原性多胜肽、至少一麻疹病毒(MeV)抗原性多胜肽、至少一人类间质肺炎病毒(hMPV)抗原性多胜肽、至少一人类副流感病毒(PIV)抗原性多胜肽、其抗原性片段或其组合。BetaCoV可为MERS-CoV、SARS-CoV、SARS-CoV-2、HCoV-OC43、HCoV-229E、HCoV-NL63、HCoV-NL、HCoV-NH、HCoV-HKU1、其变体或其组合。SARS-CoV-2发现于2019年，且亦称为COVID-19。抗原性多胜肽可为BetaCoV的棘蛋白或其抗原性片段。治疗性多胜肽可为，例如，抗体、激素、细胞激素、酵素、其衍生物或其组合。

用于导入可转录核苷酸序列的核苷酸序列可为选殖位。选殖位可为多重选殖位。选殖位可包括限制酶的识别位置、切割位置或其组合。

可将编码5’-UTR的核苷酸序列、可转录核苷酸或用于导入可转录核苷酸的核苷酸序列连接，以在体外或体内转录时形成共同转录本。

可将启动子、编码5’-UTR的核苷酸序列、可转录核苷酸或用于导入可转录核苷酸的核苷酸序列连接，以在体外或体内转录时形成共同转录本。

编码3’-UTR的核苷酸序列可进一步包括可操作地连接至3’-UTR的下游多腺苷酸或多腺苷酸附着信号(多(A)附着信号)的核苷酸序列。编码3’-UTR的核苷酸序列可包括可转录核苷酸序列或用于导入可转录核苷酸序列的核苷酸序列，且可转录核苷酸序列或用于导入可转录核苷酸序列的核苷酸序列可能在编码3’-UTR的核苷酸的上游可操作地连接至3’-UTR。

可将可转录核苷酸、或用于导入可转录核苷酸的核苷酸序列、编码3’-UTR的核苷酸序列及多腺苷酸或多腺苷酸附着信号连接，以便在体外或体内转录时形成共同转录本，或在共同转录本的3’-UTR下游添加多(A)尾。

在多核苷酸中，编码5’-UTR的核苷酸序列可包括可转录核苷酸序列或可操作地连接至5’-UTR序列的用于导入可转录核苷酸序列的核苷酸序列。在5'-UTR序列的下游，可转录核苷酸序列或用于导入可转录核苷酸序列的核苷酸序列可操作地连接至5’-UTR序列，且编码3’-UTR的核苷酸序列可包括可操作地连接至3’-UTR的下游多腺苷酸或多腺苷酸附着信号的核苷酸序列，且可能在3’-UTR序列的上游可操作地连接至可转录核苷酸序列或用于导入可转录核苷酸序列的核苷酸序列。举例而言，多核苷酸可为其中依序将下列连接的多核苷酸：编码5’-UTR的核苷酸序列、编码多胜肽的核苷酸序列或选殖位核苷酸序列、编码3’-UTR的核苷酸序列及多腺苷酸或多腺苷酸附着信号核苷酸序列。在多核苷酸中，编码5’-UTR的核苷酸序列可包括SEQ ID NO:22或31的核苷酸序列，编码3’-UTR的核苷酸序列可包括SEQ ID NO:40的核苷酸序列，且多腺苷酸的核苷酸序列可包括SEQ ID NO:41的核苷酸序列。

编码5’-UTR的核苷酸序列可包括可操作地连接至5’-UTR的上游启动子区的核苷酸序列、可转录核苷酸序列或可操作地连接至启动子的用于导入可转录核苷酸序列的核苷酸序列；可转录核苷酸序列或用于导入可转录核苷酸序列的核苷酸序列在5’-UTR序列的下游可操作地连接至5’-UTR序列；编码3’-UTR的核苷酸序列可包括可操作地连接至3’-UTR的下游多腺苷酸或多腺苷酸附着信号的核苷酸序列，且可能在3’-UTR序列的上游可操作地连接至可转录核苷酸序列或用于导入可转录核苷酸序列的核苷酸序列。举例而言，多核苷酸可为其中依序将下列连接的多核苷酸：启动子、编码5’-UTR的核苷酸序列、编码多胜肽的核苷酸序列或选殖位核苷酸序列、编码3’-UTR的核苷酸序列及多腺苷酸或多腺苷酸附着信号核苷酸序列。在多核苷酸中，编码5’-UTR的核苷酸序列可包括SEQ ID NO:22或31的核苷酸序列，编码3’-UTR的核苷酸序列可包括SEQ ID NO:40的核苷酸序列，且多腺苷酸的核苷酸序列可包括SEQ ID NO:41的核苷酸序列。

可将编码5’-UTR的核苷酸序列、编码多胜肽的核苷酸序列或选殖位核苷酸序列、编码3’-UTR的核苷酸序列及多腺苷酸或多腺苷酸附着信号连接，以便在体外或体内转录时形成共同转录本，或在共同转录本的3’-UTR下游添加多(A)尾。

可将启动子、编码5’-UTR的核苷酸序列、编码多胜肽的核苷酸序列或选殖位核苷酸序列、编码3’-UTR的核苷酸序列及多腺苷酸或多腺苷酸附着信号连接，以便在体外或体内转录时形成共同转录本，或在共同转录本的3’-UTR下游添加多(A)尾。

多核苷酸可为核酸构筑体或载体。如本文所用，“多腺苷酸附着信号”意指有助于将多腺苷酸添加至未成熟mRNA的核苷酸序列。核酸构筑体或载体可包括表达多核苷酸所需的调节序列。表达可为转录、转译或其组合。核酸构筑体或载体可包括表达构筑体或载体。

第二实施例提供了可通过使用第一实施例的多核苷酸作为模板的转录而获得的RNA。RNA可为mRNA。mRNA可包括信号序列。mRNA可包含任一选自于SEQ ID NO:63至76的核苷酸序列。mRNA可为其中序列中的至少一U通过N1-甲基-假尿苷取代的mRNA。在mRNA中，5’端的GA可具有m7(3’OMeG)(5’)ppp(5’)(2’OMeA)的帽结构。在mRNA中，所有的U皆可通过N1-甲基-假尿苷取代。mRNA可为其中所有的U皆通过N1-甲基-假尿苷取代的mRNA，且5’端的GA具有m7(3’OMeG)(5’)ppp(5’)(2’OMeA)的帽结构。

第三实施例提供了分离的多核苷酸，其包括非自然发生的5’-非转译区(5’-UTR)核苷酸序列、非自然发生或自然发生的3’-非转译区(3’-UTR)核苷酸序列或其组合。

在第三实施例的多核苷酸中，5’-UTR与SEQ ID NO:1的核苷酸序列可具有70％或以上，例如，80％或以上、90％或以上或95％或以上的序列一致性。5’-UTR可包括SEQ IDNO:1、2、3、4、5、6、7、8、9、10、11、12或其组合的序列。编码非自然发生的5’-非转译区(5’-UTR)的核苷酸序列可包括SEQ ID NO:22、23、24、25、26、27、28、29、30、31、32、33或其组合的序列。

3’-UTR可为与SEQ ID NO:15的核苷酸序列具有70％或以上，例如，80％或以上、90％或以上或95％或以上的序列一致性的3’-UTR，以及与SEQ ID NO:20的核苷酸序列具有70％或以上，例如，80％或以上、90％或以上或95％或以上的序列一致性的3’-UTR。3’-UTR可包括SEQ ID NO:14、15、16、17、18、19、20或其组合的序列。编码非自然发生或自然发生的3’-非转译区(3’-UTR)的核苷酸序列可包括SEQ ID NO:34、35、36、37、38、39、40或其组合的序列。

第三实施例的多核苷酸可包括非自然发生的5’-非转译区(5’-UTR)与自然发生的3’-非转译区(3’-UTR)。

5’-UTR核苷酸序列可包括编码多胜肽的核苷酸序列，且编码多胜肽的核苷酸序列可能在5’-UTR核苷酸的下游可操作地连接至5’-UTR。多胜肽可为抗原性多胜肽或治疗性多胜肽。抗原性多胜肽可为病毒抗原性多胜肽。病毒抗原性多胜肽可为至少一BetaCoV抗原性多胜肽、至少一RSV抗原性多胜肽、至少一MeV抗原性多胜肽、至少一hMPV抗原性多胜肽、至少一hPIV抗原性多胜肽、其抗原性片段或其组合。BetaCoV可为MERS-CoV、SARS-CoV、SARS-CoV-2、HCoV-OC43、HCoV-229E、HCoV-NL63、HCoV-NL、HCoV-NH、HCoV-HKU1、其变体或其组合。抗原性多胜肽可为BetaCoV的棘蛋白或其抗原性片段。BetaCoV的棘蛋白可为SARS-CoV-2的自然棘蛋白或其变体。变体包括α、β、γ、δ、ε及ο变体。SARS-CoV-2的自然棘蛋白或SARS-CoV-2的α、β、γ、δ、ε及ο变体的棘蛋白可分别包含SEQ ID NO:42至48的胺基酸序列。治疗性多胜肽可为，例如，抗体、激素、细胞激素、酵素、其衍生物或其组合。

5’-UTR核苷酸序列及编码多胜肽的核苷酸序列可连接在一共同转录本中。

3’-UTR核苷酸可进一步包括与其可操作地连接的下游多腺苷酸的核苷酸序列。多腺苷酸的核苷酸序列可包括，例如，20个或以上、40个或以上、80个或以上、或100个或以上，以及500个或以下、400个或以下、300个或以下、200个或以下、或150个或以下的腺苷基核苷酸。

3’-UTR核苷酸序列可包括编码多胜肽的核苷酸序列，且编码多胜肽的核苷酸序列可能在3’-UTR核苷酸序列的上游可操作地连接至3’-UTR。编码多胜肽的核苷酸序列可为核糖核苷酸序列，例如，mRNA。

编码多胜肽的核苷酸序列与3’-UTR核苷酸序列可连接在一共同转录本中。

5’-UTR可包括编码多胜肽的核苷酸序列，且编码多胜肽的核苷酸序列可能在5’-UTR序列的下游可操作地连接至5’-UTR序列，且3’-UTR可包括可操作地连接至3’-UTR的下游多腺苷酸的核苷酸序列并可在3’-UTR序列的上游连接至编码多胜肽的核苷酸序列。

5’-UTR核苷酸序列、编码多胜肽的核苷酸序列、3’-UTR核苷酸序列及多(A)尾可连接在一共同转录本中。

相较于使用自然发生的5’-UTR和/或自然发生的3’-UTR的情况，5’-UTR与3’-UTR可具有增加转译效率、编码多胜肽的核苷酸序列的稳定性或其组合的活性。

多核苷酸可为RNA，例如，mRNA。多核苷酸可包括5’端帽。术语“5’端帽”意指出现在mRNA分子的5’端的帽结构。5’端帽可包括鸟核苷酸，其通过与5’端的不寻常三磷酸键联而连接至mRNA。鸟苷可在7号位置甲基化，且为例如m⁷G或3’-O-Me-m⁷G。术语“常规5’端帽”表示自然发生的RNA 5’端帽，例如，7-甲基鸟苷(m7G)。如本文所用，术语“5’端帽”包括5’端帽类似物，其类似于RNA端帽结构并连接至RNA，且例如，经修饰以在体内和/或在细胞中具有稳定RNA的能力。可通过在5’端帽或5’端帽类似物存在下将DNA模板转录及通过以共转录方式将5’端帽或5’端帽类似物插入欲生成的RNA链中，或通过使用转录后加帽酵素(例如，牛痘病毒的加帽酵素)生成5’端帽或5’端帽类似物而将5’端帽或5’端帽类似物提供至RNA。5’端帽结构可为，例如，7mG(5’)ppp(5’)ImpNp、3’-O-Me-m7G(5’)ppp(5’)G、m7(3’OMeG)(5’)ppp(5’)(2’OMeA)或m7G(5’)ppp(5’)(2’OMeA)pG。

多核苷酸可为RNA，5’-UTR核苷酸序列可包含SEQ ID NO:1或10的核苷酸序列，3’-UTR核苷酸序列可包含SEQ ID NO:20的核苷酸序列，且多腺苷酸的核苷酸序列可包含SEQID NO:101的核苷酸序列。3’-UTR可进一步包含限制酶的识别序列。限制酶可包括XhoI、NheI、或XhoI及NheI。

在多核苷酸中，至少一U可通过N1-甲基-假尿苷取代。

多核苷酸可包含任一选自于SEQ ID NO:63至76的核苷酸序列，且多核苷酸中的至少一U可通过N1-甲基-假尿苷取代。在多核苷酸中，每一U可通过N1-甲基-假尿苷取代。

此外，多核苷酸的5’端可具有m7(3’OMeG)(5’)ppp(5’)(2’OMeA)的帽结构。

第四实施例提供了获得RNA的方法，其包括以第一实施例的多核苷酸作为模板将RNA转录。转录可包括体外、离体或体内转录。体内转录可包括在受试者中的转录。RNA可为mRNA。mRNA可包含任一选自于SEQ ID NO:63至76的核苷酸序列。mRNA可为其中序列中的至少一U通过N1-甲基-假尿苷取代的mRNA。在mRNA中，5’端的GA可具有m7(3’OMeG)(5’)ppp(5’)(2’OMeA)的帽结构。在mRNA中，所有的U皆可通过N1-甲基-假尿苷取代。mRNA可为其中所有的U皆通过N1-甲基-假尿苷取代的mRNA，且5’端的GA具有5’-[1,2-[(3’-O-甲基)m7G-(5’→5’)-ppp-Am]]的帽结构。在结构中，Am表示2’-O-甲基腺苷。然而，mRNA的5’端帽结构不局限于此结构，并可通过本领域中已知的自然发生的5’端帽结构或5’端帽类似物取代。

术语“体外转录”或“RNA体外转录”意指在非细胞系统中(亦即，在体外)合成RNA(包括mRNA)的过程。选殖载体DNA(包括质体DNA载体)可用作生成RNA转录本的模板。彼等选殖载体一般而言亦称为转录载体。RNA可通过DNA依赖性体外转录以适当DNA模板获得。DNA模板可为线性化质体DNA模板。调节RNA体外转录的启动子可为用于DNA依赖性RNA聚合酶的任意启动子。DNA依赖性RNA聚合酶可为T7 RNA聚合酶、T3 RNA聚合酶、SP6 RNA聚合酶或其组合。可通过将核酸选殖并将其导入载体中而获得用于RNA体外转录的DNA模板，以进行RNA体外转录。DNA可包括cDNA，其对应于欲在体外转录的各RNA。用于RNA体外转录的载体可为环状质体DNA。cDNA可通过mRNA的反转录或通过化学合成而获得。

转录载体可包括启动子、编码5’-UTR的核苷酸序列、编码多胜肽的序列(例如，开读框(ORF))、编码3’-UTR的核苷酸序列及多(A)尾。编码5’-UTR的核苷酸序列可包含至少一选自于SEQ ID NO:22至33的核苷酸序列。编码3’-UTR的核苷酸序列可包含至少一选自于SEQ ID NO:34至40的核苷酸序列。转录载体亦可包括大肠杆菌复制起点ColE1 ori、选择标记基因或其组合。启动子可为T7启动子。选择标记可为抗生素抗性酵素，例如，康霉素抗性酵素。

体外转录可包括通过将转录载体导入宿主细胞(例如，大肠杆菌)中而获得转形的宿主细胞，并通过培养宿主细胞而将含有质体DNA(其成为mRNA的模板)的宿主细胞增生。体外转录可包括从增生的宿主细胞(例如，大肠杆菌)中分离质体DNA。质体DNA的分离可包括从培养物中分离细胞，并从细胞中分离质体DNA。细胞的分离可通过离心、分离、沉淀或其组合进行。可通过碱萃取法、亲和性层析术、高效能液相层析术(HPLC)、电泳法或其组合从细胞中分离质体DNA。

获得RNA的方法可包括通过培养包括第一实施例的多核苷酸的细胞而产生多核苷酸的RNA转录本。RNA转录本可为mRNA。mRNA可包含任一选自于SEQ ID NO:63至76的核苷酸序列。mRNA可为其中序列中的至少一U通过N1-甲基-假尿苷取代的mRNA。在mRNA中，5’端的GA可具有5’-[1,2-[(3’-O-甲基)m7G-(5’→5’)-ppp-Am]]的帽结构。在mRNA中，所有的U皆可通过N1-甲基-假尿苷取代。在mRNA中，所有的U皆可通过N1-甲基-假尿苷取代，且5’端的GA可具有5’-[1,2-[(3’-O-甲基)m7G-(5’→5’)-ppp-Am]]的帽结构。然而，mRNA的5’端帽结构不局限于此结构，并可通过本领域中已知的自然发生的5’端帽结构或5’端帽类似物取代。

第五实施例提供了获得多胜肽的方法，其包括将第三实施例的RNA或通过第四实施例的方法获得的RNA转译。第三实施例的RNA或通过第四实施例的方法获得的RNA可为，例如，mRNA。

所述方法可包括通过培养包括第一实施例的多核苷酸的细胞而产生多胜肽。

第六实施例提供了用于将包括第三实施例的多核苷酸的多胜肽导入受试者中的组合物。第三实施例的多核苷酸可为RNA，例如，mRNA。第三实施例的多核苷酸可为通过第四实施例的方法获得的RNA。

第七实施例提供了用于诱发对多胜肽的免疫反应的组合物，其包括以第三实施例的多核苷酸作为活性成分。第三实施例的多核苷酸可为RNA，例如，mRNA。第三实施例的多核苷酸可为通过第四实施例的方法获得的RNA。

在第六实施例与第七实施例中，组合物可用于提供免疫原性或用于治疗疾病。根据所选的多胜肽，疾病可能不同。疾病可为，例如，由病毒或外来细胞引起的感染、癌症、代谢疾病、发炎性疾病、胃肠道疾病、内分泌疾病、败血症或自体免疫疾病。疾病可由酵素缺乏引起，如亨特症候群(Hunter syndrome)、高歇氏病(Gaucher disease)及法布里氏病(Fabry disease)的情况，并可以酵素替代疗法治疗。在疾病中，外来细胞可为原核细胞或真核细胞。外来细胞可为细菌。

多核苷酸可包括编码多胜肽的核苷酸序列。多胜肽可为抗原性多胜肽或治疗性多胜肽。抗原性多胜肽可为病毒抗原性多胜肽。病毒抗原性多胜肽可为至少一BetaCoV抗原性多胜肽、至少一RSV抗原性多胜肽、至少一MeV抗原性多胜肽、至少一hMPV抗原性多胜肽、至少一hPIV抗原性多胜肽、其抗原性片段或其组合。BetaCoV可为MERS-CoV、SARS-CoV、SARS-CoV-2、HCoV-OC43、HCoV-229E、HCoV-NL63、HCoV-NL、HCoV-NH、HCoV-HKU1、其变体或其组合。抗原性多胜肽可为BetaCoV的棘蛋白或其抗原性片段。治疗性多胜肽可为，例如，抗体、激素、细胞激素、酵素、其衍生物或其组合。组合物可用于预防、治疗或诊断受试者的症状或感染。受试者可为哺乳动物，包括人类。感染可为细菌或病毒感染。病毒可为BetaCoV、RSV、MeV、hMPV或hPIV。BetaCoV可为MERS-CoV、SARS-CoV、SARS-CoV-2、HCoV-OC43、HCoV-229E、HCoV-NL63、HCoV-NL、HCoV-NH、HCoV-HKU1、其变体或其组合。组合物可用于启动免疫效应子细胞。举例而言，组合物可用于离体活化周边血液单核细胞(PBMC)，并输入受试者体内。组合物可用于诱发对SARS-CoV-2或其变体的免疫反应。组合物可用于预防通过SARS-CoV-2或其变体的感染。

组合物可注射至受试者体内，且RNA多核苷酸(例如，mRNA)可在体内转译以产生抗原性多胜肽。

一“有效量”的组合物，其包括具有至少一编码抗原性多胜肽的可转译区的多核苷酸，可与细胞、组织或受试者接触。

有效量可根据标靶组织、标靶细胞、投予方式、多核苷酸的物理性质(例如，多核苷酸的大小与多核苷酸中修饰的核苷的量)及组合物的其他组分而确定。一般而言，一有效量的组合物可导致诱发的或增强的免疫反应，以作为细胞中抗原产生的功能。

组合物可与其他预防性或治疗性化合物一起投予。预防性或治疗性化合物可为，例如，佐剂或追加剂。如本文所用，当提及预防性组合物(例如疫苗)时，术语“追加剂”意指额外投予预防性组合物。追加剂或追加剂疫苗可在早期投予预防性组合物之后给予。初始投予预防性组合物与投予追加剂之间的时间可为1周、2周、3周、1个月、2个月、3个月、6个月或1年。此外，组合物可不包括佐剂。

组合物可经由肌内途径、皮下途径、皮内途径、鼻内途径或肺部途径投予。

组合物可包括至少一药学上可接受的赋形剂。组合物中的多核苷酸可与赋形剂一起配制或可与赋形剂一起制成复合物。赋形剂可为本领域中已知。

如本文所用，术语“活性成分”意指组合物或其中包含的多核苷酸，例如，RNA多核苷酸，包括mRNA。RNA多核苷酸可为，例如，编码抗原性多胜肽或治疗性多胜肽。

组合物中包含的活性成分、药学上可接受的赋形剂和/或其他额外组分的相对量可取决于欲治疗的受试者的身份与大小和/或投予条件与途径而变。举例而言，组合物可包括0.1％至100％，例如，0.5％至50％、1.0％至30％、5.0％至80％或80％(w/w)或以上的活性成分。

在组合物中，多核苷酸可为mRNA。mRNA可包括稳定元件，稳定元件包括5’-UTR和/或3’-UTR。mRNA可进一步包括额外的结构，例如5’端帽结构或3’端多(A)尾。5’-UTR与3’-UTR一般从基因体DNA转录，且为未成熟mRNA的元件。成熟mRNA的结构特征(例如5’端帽与3’端多(A)尾)一般而言在mRNA加工过程中被添加至转录的(未成熟)mRNA。多(A)尾为一段腺嘌呤核苷酸，一般而言被添加至转录的mRNA。多(A)尾可包括，例如，400个或以下的腺嘌呤核苷酸。在一些实施例中，一段3’端多(A)尾可为单独mRNA的稳定性的基本元件。

组合物可配制成纳米颗粒。纳米颗粒可用于将多核苷酸(例如mRNA)递输至细胞中，且为本领域中已知。举例而言，纳米颗粒可为用于疫苗(例如，RNA疫苗)的已知纳米颗粒，以诱发对COVID-19的免疫反应。纳米颗粒可为脂质纳米颗粒(LNP)。组合物可配制成脂质纳米颗粒(LNP)或可结合至LNP。所述结合可以包括LNP内的结合或LNP表面的结合。举例而言，组合物可配制在脂质多阳离子复合物内部或可结合至脂质多阳离子复合物。脂质多阳离子复合物亦称为阳离子脂质纳米颗粒。多阳离子可包括MC3、Lipid 319、C12-200、5A2-SC8、306Oi10、Moderna Lipid 5、Acuitas A9、SM-102、ALC-0315、Arcturus Lipid 2,2(8,8)4C CH3、Genevant CL1、阳离子多胜肽，例如聚离胺酸、聚鸟胺酸和/或聚精胺酸。此外，组合物可配制在脂质纳米颗粒内部或结合至脂质纳米颗粒，脂质纳米颗粒包括非阳离子脂质，例如二硬脂酰基磷脂酰胆碱(DSPC)、1,2-二硬脂酰基-sn-甘油-3-磷酸胆碱(DSPC)、二棕榈酰基磷脂酰胆碱(DPPC)、固醇(例如胆固醇)或二油酰基磷脂酰乙醇胺(DOPE)。此外，组合物可配制在脂质纳米颗粒内部或结合至脂质纳米颗粒，其包括聚乙二醇(PEG)-脂质，例如1,2-二肉豆蔻酰基-rac-甘油-3-甲氧基聚乙二醇-2000(PEG2000-DMG)、2-[(聚乙二醇)-2000]-N,N-二十四基乙酰胺(ALC-0159)、聚乙二醇二甲基丙烯酸酯(PEG-DMA)。

脂质纳米颗粒制剂可包括阳离子脂质、磷脂质、固醇(例如胆固醇)、PEG-脂质或其组合。脂质纳米颗粒制剂可包括，例如，阳离子脂质、磷脂质、固醇(例如胆固醇)及PEG-脂质。此外，脂质纳米颗粒可包括PEG-修饰的脂质、非阳离子脂质、固醇、可离子化脂质或其组合。脂质纳米颗粒可包括0.5摩尔％至15摩尔％的PEG-修饰的脂质、5摩尔％至25摩尔％的非阳离子脂质、25摩尔％至55摩尔％的固醇及20摩尔％至60摩尔％的可离子化脂质。PEG-修饰的脂质可为1,2-二肉豆蔻酰基-sn-甘油甲氧基聚乙二醇(PEG2000-DMG)，非阳离子脂质可为1,2-二硬脂酰基-sn-甘油-3-磷酸胆碱(DSPC)，固醇可为胆固醇，且可离子化阳离子脂质可为下列化合物1的结构：

PEG-修饰的脂质可为下列化合物2(ALC-0159)的结构，非阳离子脂质可为1,2-二硬脂酰基-sn-甘油-3-磷酸胆碱(DSPC)，固醇可为胆固醇，且可离子化的阳离子脂质可为下列化合物3(ALC-0315)的结构：

组合物可为用于诱发对SARS-CoV-2或其变体的免疫反应的组合物，其包括多核苷酸及脂质纳米颗粒(LNP)，以作为活性成分。组合物可用于预防SARS-CoV-2或其变体的感染。

第八实施例提供了使用多核苷酸的方法，其包括将多核苷酸导入宿主细胞中。第三实施例的多核苷酸可为RNA，例如，mRNA。第三实施例的多核苷酸可为RNA，例如，mRNA。

在所述方法中，多核苷酸可为RNA，其包括mRNA。宿主细胞可为任何衍生自受试者的细胞。受试者可为哺乳动物，包括人类。细胞可为，例如，干细胞、生殖细胞或体细胞。在上述方法中，多核苷酸可为RNA，且宿主细胞可为抗原提供细胞，其包括树突细胞、单核细胞或巨噬细胞。

所述方法可包括将第三实施例的多核苷酸注射至受试者体内。投予可为非口服或口服投予。投予可为肌内、皮下、皮内、鼻内或肺部投予。受试者可为哺乳动物，包括人类。

所述方法可使受试者对多胜肽免疫。此外，所述方法可治疗受试者的疾病。多胜肽可为BetaCoV的抗原蛋白。BetaCoV可为MERS-CoV、SARS-CoV、SARS-CoV-2、HCoV-OC43、HCoV-229E、HCoV-NL63、HCoV-NL、HCoV-NH、HCoV-HKU1、其变体或其组合。所述方法可在受试者体内诱发对BetaCoV(例如，对其棘蛋白或其变体或次单元)的免疫反应。所述方法可预防感染BetaCoV，例如，MERS-CoV、SARS-CoV、SARS-CoV-2、HCoV-OC43、HCoV-229E、HCoV-NL63、HCoV-NL、HCoV-NH、HCoV-HKU1或其变体或组合。

在第三至第八实施例中，多核苷酸可包括5’端帽。5’端帽可为7mG(5’)ppp(5’)ImpNp、3’-O-Me-m7G(5’)ppp(5’)G或m7G(5’)ppp(5’)(2’OMeA)pG。

在第三至第七实施例中，多核苷酸可包括具有至少一化学修饰的核苷酸。修饰可在整个核苷酸中一致地进行。如本文所用，“化学修饰”与“化学上修饰”意指腺苷(A)、鸟苷(G)、尿苷(U)、胸腺嘧啶(T)或胞苷(C)的核糖核苷酸或去氧核糖核苷酸的位置、样式、百分比或群体的至少一修饰。一般而言，彼等术语并非意指mRNA帽部分的自然发生的5’端中的核糖核苷酸的修饰。

多核苷酸，例如RNA(包括mRNA)，可包括一或多个其他修饰。多核苷酸的特定区域可包括核苷或核苷酸的至少一修饰。当导入细胞或受试者中时，相较于未修饰的多核苷酸，修饰的多核苷酸在细胞或受试者中可显示降解减少。此外，当导入细胞或受试者中时，相较于未修饰的多核苷酸，修饰的多核苷酸在细胞或受试者中可显示免疫原性降低(例如，先天反应降低)。

具有修饰的胞嘧啶的核苷可包括N4-乙酰基-胞苷(ac4C)、5-甲基-胞苷(m5C)、5-卤-胞苷(例如，5-碘-胞苷)、5-羟甲基-胞苷(hm5C)、1-甲基-假异胞苷、2-硫-胞苷(s2C)、2-硫-5-甲基-胞苷或其组合。

具有修饰的腺嘌呤的核苷可包括7-去氮杂-腺嘌呤、1-甲基-腺苷(m1A)、2-甲基-腺嘌呤(m2A)、N6-甲基-腺苷(m6A)或其组合。

具有修饰的鸟嘌呤的核碱基或核苷可包括肌苷(I)、1-甲基-肌苷(m1I)、怀俄苷(wyosine(imG))、甲基怀俄苷(mimG)、7-去氮杂-鸟苷、7-氰基-7-去氮杂-鸟苷(preQ0)、7-胺基甲基-7-去氮杂-鸟苷(preQ1)、7-甲基-鸟苷(m7G)、1-甲基-鸟苷(m1G)、8-侧氧基-鸟苷、7-甲基-8-侧氧基-鸟苷或其组合。

具有化学修饰的核苷酸可为假尿苷、N1-甲基假尿苷、N1-乙基假尿苷、2-硫尿苷、4’-硫尿苷、5-甲基胞嘧啶、5-甲基尿苷、2-硫-1-甲基-1-去氮杂-假尿苷、2-硫-1-甲基-假尿苷、2-硫-5-氮杂-尿苷、2-硫-二氢假尿苷、2-硫-二氢尿苷、2-硫-假尿苷、4-甲氧基-2-硫-假尿苷、4-甲氧基-假尿苷、4-硫-1-甲基-假尿苷、4-硫-假尿苷、5-氮杂-尿苷、二氢假尿苷、5-甲氧基尿苷、2’-O-甲基尿苷或其组合。化学修饰可位于尿嘧啶的第5号位置。化学修饰可为将尿嘧啶修饰成N1-甲基假尿苷。化学修饰可为将尿嘧啶修饰成N1-乙基假尿苷。

本发明的效果

根据一实施例的分离的多核苷酸，其包括编码非自然发生的5’-非转译区(5’-UTR)的核苷酸序列、编码非自然发生或自然发生的3’-非转译区(3’-UTR)的核苷酸序列或其组合，可用于稳定mRNA，从而增加转译效率。

根据另一实施例的RNA相当稳定并具有高转译效率，因此，可用于有效地转译RNA。

根据一实施例的分离的多核苷酸相当稳定并具有高转译效率，因此，可用于有效地转译RNA。

当使用根据另一实施例而获得RNA的方法时，可有效地获得RNA。

当使用根据另一实施例而获得多胜肽的方法时，可有效地获得多胜肽。

根据另一实施例的免疫原性组合物可用于有效地使受试者免疫。

使用根据另一实施例的多核苷酸的方法可用于有效地使受试者免疫。

附图说明

图1显示产生编码SARS-CoV-2棘蛋白或其变体的mRNA的制备载体；

图2A、2B及2C显示以层析术分析产生的mRNA的结果；以及

图3显示当将产生的mRNA-脂质纳米颗粒(LNP)被导入细胞中时，通过使用西方墨点法鉴定棘蛋白的表达的结果。

具体实施方式

在下文中，将通过范例更详细地描述本揭示。然而，彼等范例旨在说明本揭示，且本揭示的范畴不局限于彼等范例。

范例1：5’-UTR序列增加编码mRNA的基因的表达

设计了5’-UTR序列，其增加编码mRNA的基因的表达。

其结果为，获得12个非自然发生的5’-UTR序列，其具有SEQ ID NO:1至12的核苷酸序列。SEQ ID NO:2的核苷酸序列为其中形成稳定发夹结构的序列(GUCCCUCUGA，SEQ IDNO:13)在SEQ ID NO:1的核苷酸序列中朝5’端方向移动的序列。SEQ ID NO:3的核苷酸序列为其中在SEQ ID NO:1的核苷酸序列中的一部分鸟嘌呤通过尿苷取代的序列。

SEQ ID NO:4的核苷酸序列为其中在SEQ ID NO:1的核苷酸序列中的一部分通过连续的尿苷取代的序列。SEQ ID NO:5、6、7及8的核苷酸序列各为在SEQ ID NO:1的核苷酸序列中的一部分通过富含腺嘌呤的序列取代的序列。SEQ ID NO:9、10及11的核苷酸序列为其中在SEQ ID NO:6的核苷酸序列中的一部分通过另一核苷酸任意地取代的序列。

SEQ ID NO:12的核苷酸序列为其中在SEQ ID NO:5的核苷酸序列中添加至少一鸟嘌呤的序列。

SEQ ID NO:1至12的核苷酸序列中的各核苷酸可从自然发生的形式中修饰。举例而言，在序列中的至少一U可通过N1-甲基-假尿苷取代。在序列中的所有U皆可通过N1-甲基-假尿苷取代。

范例2：3’-UTR序列增加编码mRNA的基因的表达

设计了3’-UTR序列，其增加编码mRNA的基因的表达。

其结果为，获得7个3’-UTR序列，其具有SEQ ID NO:14至20的核苷酸序列。

SEQ ID NO:14的核苷酸序列可为不包括miRNA结合位的序列。SEQ ID NO:15至18的核苷酸序列可包括富含CU的元件(UCCACCCCCCCAUCUCC，SEQ ID NO:21)。

SEQ ID NO:16与19的核苷酸序列可包括抗原-R结合元件(UUGGUUU)。

SEQ ID NO:14至20的核苷酸序列中的各核苷酸可从自然发生的形式中修饰。举例而言，序列中的至少一U可通过N1-甲基-假尿苷取代。序列中的所有U皆可通过N1-甲基-假尿苷取代。

范例3：使用非自然发生的5’-UTR序列与3’-UTR序列制备模板载体

通过可操作地连接而制备载体：至少一编码非自然发生的5’-UTR核苷酸序列的序列，其包含SEQ ID NO:1至12的核苷酸序列；至少一编码3’-UTR核苷酸序列的序列，其包含SEQ ID NO:14至20的核苷酸序列；以及编码多胜肽的基因。

具体而言，载体可为其中将下列连接的载体：启动子；编码5’-UTR的核苷酸序列；编码多胜肽的开读框(ORF)；编码3’-UTR的核苷酸序列；以及多(A)尾。针对编码5’-UTR的核苷酸序列，使用至少一选自于SEQ ID NO:22至33的核苷酸序列。针对编码3’-UTR的核苷酸序列，使用至少一选自于SEQ ID NO:109至115的核苷酸序列。SEQ ID NO:109至115的核苷酸序列对应于SEQ ID NO:34至40的核苷酸序列，其包含在其5端的XhoI酵素识别序列及在其3端的NheI酵素识别序列。

编码多(A)尾的核苷酸序列具有SEQ ID NO:41的核苷酸序列。载体亦可包括大肠杆菌复制起点ColE1 ori及选择标记基因。启动子可为T7启动子。选择标记可为康霉素抗性酵素。

当编码所选非自然发生的5’-UTR的核苷酸序列和/或编码3’-UTR的核苷酸序列连接至编码多胜肽的序列时，多胜肽的产量增加，且mRNA(其包括非自然发生的5’-UTR序列、编码多胜肽的序列及3’-UTR序列)的稳定性显著增加。多胜肽可为各具有SEQ ID NO:42至48的胺基酸序列的SARS-CoV-2棘蛋白，或其α、β、γ、δ、ε及ο变体。编码SARS-CoV-2棘蛋白或其α、β、γ、δ、ε及ο变体的多核苷酸可具有SEQ ID NO:49至55的核苷酸序列，且其mRNA可各具有SEQ ID NO:56至62的核苷酸序列。编码多胜肽(例如，SARS-CoV-2棘蛋白或其变体)的mRNA的选殖流程如下。

(1)制备用于产生SARS-CoV-2棘蛋白或其变体的mRNA的模板载体

制备用于产生SARS-CoV-2棘蛋白或其变体和/或蛋白产物的mRNA的载体，其中载体包括编码12个设计的5’-UTR序列的核苷酸序列的一者、编码SARS-CoV-2棘蛋白或其变体的核苷酸序列的一者、编码7个3’-UTR序列的核苷酸序列的一者及多(A)尾，并将载体导入微生物细胞中，且培养所得的微生物细胞以产生选殖载体。通过以产生的载体作为模板的体外转录，产生mRNA。变体包括α、β、γ、δ、ε及ο变体。

具体而言，从pUC57-Amp^R载体(Addgene)产生pUC57-Kan^R载体，其中抗生素抗性基因通过康霉素抗性基因取代。产生的pUC57-Kan^R载体以限制酶HindIII与EcoRI处理而切割，且切割的载体通过使用连接酶连接至以合成方式制备的编码SARS-CoV-2棘蛋白或其变体的多核苷酸，获得插入的具有编码SARS-CoV-2棘蛋白或其变体的序列的pUC57-Kan^R载体。编码SARS-CoV-2棘蛋白或其变体的多核苷酸具有SEQ ID NO:49至55的核苷酸序列。插入的编码棘蛋白或其变体的多核苷酸包括编码5’-UTR序列的核苷酸序列与编码SARS-CoV-2棘蛋白或其变体的序列，且编码SARS-CoV-2棘蛋白的核苷酸序列的5’端的第879个核苷酸为BamHI限制酶识别序列，且识别序列随后被切割以导入编码设计的5’-UTR序列的核苷酸序列。

(2)连接编码5’-UTR序列的核苷酸序列与编码SARS-CoV-2棘蛋白或其变体的核苷酸序列

为了以编码选自于SEQ ID NO:1至12的序列的5’-UTR序列的核苷酸序列取代制备的模板载体的5’-UTR序列，通过PCR反应获得含有编码5’-UTR的核苷酸序列的DNA片段，其中引子组为包括编码5’-UTR的核苷酸序列的引子与包括SARS-CoV-2棘蛋白的BamHI限制酶识别序列的序列的引子，并以模板载体作为模板。为了更可靠地获得含有编码5’-UTR的核苷酸序列的DNA片段，每一序列进行两个流程的PCR反应。在使用一次引子进行第一次PCR之后，以所得的DNA作为模板并使用二次引子进行第二次PCR，因此，获得含有编码5’-UTR的核苷酸序列的DNA片段。本文中使用的引子序列为SEQ ID NO:77至100的多核苷酸。

以限制酶HindIII与BamHI处理PCR反应所得的含有编码12个5’-UTR的核苷酸序列的各DNA片段及(1)中制备的模板载体而进行切割，并通过使用连接酶将切割的序列连接。其结果为，制得编码SARS-CoV-2棘蛋白或其变体的载体，其中编码5’-UTR的核苷酸序列通过编码选自于SEQ ID NO:1至12的序列的5’-UTR的各核苷酸序列取代。

(3)连接编码3’-UTR的核苷酸序列

在(2)中制备的载体中，其编码SARS-CoV-2棘蛋白或其变体，其中编码5’-UTR的核苷酸序列通过编码选自于SEQ ID NO:22至33的序列的5’-UTR的各核苷酸序列取代，编码选自于SEQ ID NO:109至115的序列的3’-UTR的各核苷酸序列连接至编码SARS-CoV-2棘蛋白或其变体的序列的3’端。SEQ ID NO:109至115的各核苷酸序列对应于SEQ ID NO:34至40的核苷酸序列，其包含在其5端的XhoI酵素识别序列及在其3端的NheI酵素识别序列。

具体而言，以合成方式获得编码选自于SEQ ID NO:109至115的序列的3’-UTR的各核苷酸序列。SEQ ID NO:102至108的各核苷酸序列为对应于SEQ ID NO:109至115的各核苷酸序列的RNA序列。

通过XhoI与NheI限制酶切割(2)中制备所得的序列与模板载体，并通过使用DNA连接酶将产物连接。其结果为，制得包括编码5’-UTR的序列-编码SARS-CoV-2棘蛋白或其变体的序列-编码3’-UTR的序列的结构的载体。在此，编码5’-UTR的序列意指编码选自于SEQ IDNO:22至33的序列的5’-UTR序列的各序列。编码3’-UTR的核苷酸序列意指编码选自于SEQID NO:109至115的序列的3’-UTR序列的各核苷酸序列。编码SARS-CoV-2棘蛋白或其变体的序列表示SEQ ID NO:42至48的各SARS-CoV-2或其变体的各胺基酸序列。

(4)连接连续的腺嘌呤核苷酸

在包括编码5’-UTR的序列-编码SARS-CoV-2棘蛋白或其变体的序列-编码3’-UTR的序列的结构的载体中，将连续的腺嘌呤核苷酸序列连接至编码3’-UTR序列的3’端。

以合成方式获得多腺苷酸，其中将NheI与EcoRI序列个别添加至SEQ ID NO:41的连续腺苷酸序列的5’-端与3’-端。各通过NheI与EcoRI限制酶切割所得的序列与模板载体，并通过使用DNA连接酶将切割的产物连接。

其结果为，制备包括编码5’-UTR的序列-编码SARS-CoV-2棘蛋白或其变体的序列-编码3’-UTR-多(A)尾的序列的结构的载体。在此，编码5’-UTR的序列、编码3’-UTR的序列及编码SARS-CoV-2棘蛋白或其变体的序列如上述。此外，多(A)尾具有SEQ ID NO:41的核苷酸序列。

图1显示用于产生编码制备的SARS-CoV-2棘蛋白或其变体的mRNA的载体。

范例4：使用非自然发生的5’-UTR序列与3’-UTR序列产生基因产物

将范例3制备的载体，其包括编码5’-UTR的序列-编码SARS-CoV-2棘蛋白或其变体的序列-编码3’-UTR-多(A)尾的序列的结构，导入大肠杆菌中以获得转形的大肠杆菌，并培养所得的大肠杆菌，使含有质体DNA(其为mRNA的模板)的大肠杆菌增殖。通过高速离心，从培养基中分离增殖的大肠杆菌，并通过使用本领域中已知的碱萃取法而获得细胞衍生的模板DNA。通过使用位于多(A)尾末端的限制酶识别序列，将所得的模板DNA线性化。通过使用线性化、细胞衍生的模板DNA的体外转录，产生具有5’-UTR的核苷酸序列-编码SARS-CoV-2棘蛋白或其变体的序列-3’-UTR-多(A)尾的mRNA。在此，编码5’-UTR、3’-UTR、多(A)尾及SARS-CoV-2棘蛋白或其变体的序列如上述。

具体而言，将5U/μl的T7 RNA聚合酶添加至含有10ng/μl的线性化质体DNA、4mM的Reagent AG、5mM的NTP、5mM的N1-甲基假尿苷、20mM的镁离子盐、10mM的DTT、0.01U/μl的无机焦磷酸酶(PPase)及1U/μl的RNAse抑制剂的水溶液中，且反应混合物在37℃下培养至少1小时，从而进行体外转录反应。/>Reagent AG为用于mRNA转录与共转录加帽的试剂，并形成m7G(5’)ppp(5’)(2’OMeA)pG的帽结构。以DNAse处理反应产物，并通过使用/>RNA Cleanup Kit(New England Biolabs)纯化RNA。其结果为，产生具有SEQ ID NO:63至76的核苷酸序列的mRNA。包括在mRNA中的5’-UTR、SARS-CoV-2棘蛋白或其变体的序列、3’-UTR及多(A)尾的核苷酸序列如下表1所示。

[表1]

图2A、2B及2C显示在所产生的mRNA中，具有SEQ ID NO:67、70或76的核苷酸序列的mRNA的层析术分析结果。图2A、2B及2C中的最大峰值分别显示具有SEQ ID NO:67、70或76的核苷酸序列的mRNA。如图2A、2B及2C所示，具有SEQ ID NO:67、70或76的核苷酸序列的mRNA的纯度分别为83.0％、81.9％及83.1％。

范例5：制备负载基因产物mRNA的脂质纳米颗粒

以46.3:9.4:42.7:1.6的摩尔比率将作为可离子化脂质的ALC-0315，((4-羟丁基)氮烷二基)双(己烷-6,1-二基)双(2-己基癸酸酯))(BLDpharm Ltd.，China)、作为磷脂质的(二硬脂酰基磷脂酰胆碱，DSPC)(Avanti，USA)、作为胆固醇的Synthechol(Sigma，USA)、作为脂质-PEG共轭体的ALC-0159，2-[(聚乙二醇)-2000]-N,N-二十四基乙酰胺(SINOPEG，China)溶解于乙醇中，以制备脂质复合物溶液。

将0.3mg的范例4中制备的mRNA在100mM的乙酸钠中稀释至0.08mg/mL，以获得含有mRNA的溶液。所得的mRNA溶液与脂质复合物溶液在12mL/min的流速下以5:1的体积比率注入微流体装置(Ignite Nanoassemblr；PNI，Canada)的各微流道中，以便mRNA与脂质复合物的重量比率可为1:25.4，因此，使mRNA溶液与脂质复合物溶液混合。通过混合，将脂质复合物溶液中的乙醇稀释成临界乙醇浓度，并形成负载mRNA的脂质纳米颗粒。微流体装置包括由两个微通道汇合形成的微通道，且为允许两种溶液在流动时混合的装置，例如，通过使mRNA溶液在一微通道中流动及使脂质复合物溶液在另一微通道中流动。通过微流体装置的微通道溶析的混合物为负载mRNA的脂质纳米颗粒(LNP)。

将制备的负载mRNA的LNP充填在10,000Da的离心过滤器上，并将缓冲液更换成含有0.45mM的氯化钾、0.24mM的磷酸二氢钾、20.53mM的氯化钠、1.31mM的磷酸氢二钠及2％的蔗糖的缓冲液(pH 6.9至pH 7.9)。之后，将含有负载mRNA的LNP溶液的缓冲液过滤通过0.2μm过滤器，以制备最终的负载mRNA的LNP。

范例6：鉴定脂质纳米颗粒的性质

(1)鉴定脂质纳米颗粒的封装效率

根据制造商的说明，通过使用Quant-iT RiboGreen RNA Kit(Invitrogen，USA)，鉴定范例5中制备的负载mRNA的LNP(以下亦称为“mRNA-LNP”)的负载或封装效率(％)。具体而言，将套组中的Triton-X与负载mRNA的LNP混合，使LNP变性以释放mRNA。将混合溶液添加至含有Ribogreen试剂的各孔中，检测Ribogreen试剂发出的荧光，以检测释放的mRNA。根据下列公式计算封装效率。

封装效率(％)＝(以Triton X处理的LNP的荧光–未以Triton X处理的LNP的荧光)/(以Triton X处理的LNP的荧光)x 100

[表2]

如表2所示，野生型S、δS及οS mRNA-LNP经鉴定以高的封装效率负载mRNA。

(2)鉴定脂质纳米颗粒的尺寸

通过使用Zetasizer NanoZS(Malvern Instruments，UK)，鉴定范例5中制备的mRNA-LNP的粒径与多分散性指数(PDI)。Zetasizer为通过使用动态光散射技术而确定粒径与粒径分布的装置。表3显示测量粒径与多分散性指数的结果。

[表3]

如表3所示，野生型S、δS及οS mRNA-LNP的粒径在80nm至100nm的范围内。

范例7：鉴定HEK293T细胞中的mRNA表达

将范例5中制备的含有mRNA的脂质纳米颗粒递输至HEK293T细胞并鉴定mRNA表达。为此，进行如下的体外实验。

在将HEK293T细胞以6x10⁵个细胞/2mL/孔接种至6孔培养盘中24小时之后，各添加0.5μg或2μg的脂质纳米颗粒，并培养24小时。在37℃的培养基中进行培养。在培养之后，将160μl/孔的哺乳动物蛋白萃取试剂(M-PER^TM)(Thermo Scientific^TM，Cat No.78501)，一裂解缓冲液，添加至各孔中，使细胞破裂并萃取蛋白，并通过使用Pierce^TM BCA ProteinAssay Kit(Thermo Scientific^TM，Cat No.23225)，进行二喹啉甲酸试验(BCA)蛋白定量。所得的试剂通过裂解缓冲液与5x还原染料(10％的SDS、0.5％的溴酚蓝、50％的甘油、0.5％的2-巯基乙醇、250mM的tris，pH 6.8)稀释，以便蛋白浓度可变得相等。通过使用抗SARS-CoV-2棘S1次单元单株抗体(R&Dsystems，Cat No.MAB105403)，针对所得的稀释样品进行西方墨点法实验。

图3显示在将产生的mRNA-脂质纳米颗粒(LNP)导入细胞中时，通过使用西方墨点法鉴定棘蛋白的表达的结果。如图3所示，S蛋白的表达随着mRNA-LNP处理浓度的增加而增加。

序列表

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ccacaccccc auucccccac uccagauaaa gcuucaguua uaucucacgu gucuggaguu 60

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<212> RNA

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<212> RNA

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<212> DNA

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<220>

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<212> DNA

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<220>

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<220>

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<212> DNA

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<220>

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agtgctcccc atccaactaa actgtccctc tgtccgaact aaactgcact gtcccagcac 60

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<212> DNA

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<220>

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<220>

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<212> DNA

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ccacaccccc attcccccac tccagataaa gcttcagtta tatctcacgt gtctggagtt 60

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ccacaccccc attcccccac tccagataaa gcttcagtta tatctcacgt gtctggagtt 60

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Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val

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Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe

20 25 30

Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu

35 40 45

His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp

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Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp

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Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu

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Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser

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Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile

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Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr

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Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr

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Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu

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Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe

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Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr

195 200 205

Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu

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Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr

225 230 235 240

Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser

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Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro

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Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala

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Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys

290 295 300

Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val

305 310 315 320

Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys

325 330 335

Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala

340 345 350

Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu

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Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro

370 375 380

Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe

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Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly

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Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys

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Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn

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Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe

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Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys

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Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly

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Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val

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Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys

515 520 525

Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn

530 535 540

Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu

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Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val

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Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe

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Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val

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Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile

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His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser

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Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val

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Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala

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Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala

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Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser

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Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile

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Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val

725 730 735

Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu

740 745 750

Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr

755 760 765

Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln

770 775 780

Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe

785 790 795 800

Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser

805 810 815

Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly

820 825 830

Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp

835 840 845

Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu

850 855 860

Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly

865 870 875 880

Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile

885 890 895

Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr

900 905 910

Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn

915 920 925

Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala

930 935 940

Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn

945 950 955 960

Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val

965 970 975

Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln

980 985 990

Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val

995 1000 1005

Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn

1010 1015 1020

Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys

1025 1030 1035

Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro

1040 1045 1050

Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val

1055 1060 1065

Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His

1070 1075 1080

Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn

1085 1090 1095

Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln

1100 1105 1110

Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val

1115 1120 1125

Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1130 1135 1140

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn

1145 1150 1155

His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn

1160 1165 1170

Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu

1175 1180 1185

Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu

1190 1195 1200

Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu

1205 1210 1215

Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met

1220 1225 1230

Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys

1235 1240 1245

Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro

1250 1255 1260

Val Leu Lys Gly Val Lys Leu His Tyr Thr

1265 1270

<210> 43

<211> 1270

<212> PRT

<213> SARS-CoV-2

<400> 43

Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val

1 5 10 15

Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe

20 25 30

Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu

35 40 45

His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp

50 55 60

Phe His Ala Ile Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro

65 70 75 80

Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser

85 90 95

Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr

100 105 110

Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile Lys Val

115 120 125

Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr His Lys

130 135 140

Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala

145 150 155 160

Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu

165 170 175

Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys

180 185 190

Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn

195 200 205

Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val

210 215 220

Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala

225 230 235 240

Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr

245 250 255

Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe

260 265 270

Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys

275 280 285

Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr

290 295 300

Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr

305 310 315 320

Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly

325 330 335

Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg

340 345 350

Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser

355 360 365

Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu

370 375 380

Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg

385 390 395 400

Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala

405 410 415

Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala

420 425 430

Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr

435 440 445

Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp

450 455 460

Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val

465 470 475 480

Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro

485 490 495

Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe

500 505 510

Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr

515 520 525

Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr

530 535 540

Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln

545 550 555 560

Gln Phe Gly Arg Asp Ile Asp Asp Thr Thr Asp Ala Val Arg Asp Pro

565 570 575

Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val

580 585 590

Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu

595 600 605

Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp

610 615 620

Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe

625 630 635 640

Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser

645 650 655

Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln

660 665 670

Thr Gln Thr Asn Ser His Arg Arg Ala Arg Ser Val Ala Ser Gln Ser

675 680 685

Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr

690 695 700

Ser Asn Asn Ser Ile Ala Ile Pro Ile Asn Phe Thr Ile Ser Val Thr

705 710 715 720

Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr

725 730 735

Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln

740 745 750

Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala

755 760 765

Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln

770 775 780

Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser

785 790 795 800

Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu

805 810 815

Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys

820 825 830

Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys

835 840 845

Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp

850 855 860

Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr

865 870 875 880

Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala

885 890 895

Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val

900 905 910

Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile

915 920 925

Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys

930 935 940

Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val

945 950 955 960

Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp

965 970 975

Ile Leu Ala Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg

980 985 990

Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln

995 1000 1005

Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala

1010 1015 1020

Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp

1025 1030 1035

Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala

1040 1045 1050

Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln

1055 1060 1065

Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys

1070 1075 1080

Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His

1085 1090 1095

Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr

1100 1105 1110

Thr His Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly

1115 1120 1125

Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp

1130 1135 1140

Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser

1145 1150 1155

Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val

1160 1165 1170

Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1175 1180 1185

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr

1190 1195 1200

Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile

1205 1210 1215

Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys

1220 1225 1230

Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly

1235 1240 1245

Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys

1250 1255 1260

Gly Val Lys Leu His Tyr Thr

1265 1270

<210> 44

<211> 1270

<212> PRT

<213> SARS-CoV-2

<400> 44

Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val

1 5 10 15

Asn Phe Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe

20 25 30

Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu

35 40 45

His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp

50 55 60

Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Ala

65 70 75 80

Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu

85 90 95

Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser

100 105 110

Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile

115 120 125

Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr

130 135 140

Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr

145 150 155 160

Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu

165 170 175

Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe

180 185 190

Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr

195 200 205

Pro Ile Asn Leu Val Arg Gly Leu Pro Gln Gly Phe Ser Ala Leu Glu

210 215 220

Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr

225 230 235 240

Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr

245 250 255

Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe

260 265 270

Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys

275 280 285

Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr

290 295 300

Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr

305 310 315 320

Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly

325 330 335

Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg

340 345 350

Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser

355 360 365

Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu

370 375 380

Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg

385 390 395 400

Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile Ala

405 410 415

Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala

420 425 430

Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr

435 440 445

Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp

450 455 460

Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val

465 470 475 480

Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro

485 490 495

Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe

500 505 510

Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr

515 520 525

Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr

530 535 540

Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln

545 550 555 560

Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro

565 570 575

Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val

580 585 590

Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu

595 600 605

Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp

610 615 620

Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe

625 630 635 640

Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser

645 650 655

Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln

660 665 670

Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala Ser Gln Ser

675 680 685

Ile Ile Ala Tyr Thr Met Ser Leu Gly Val Glu Asn Ser Val Ala Tyr

690 695 700

Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr

705 710 715 720

Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr

725 730 735

Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln

740 745 750

Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala

755 760 765

Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln

770 775 780

Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser

785 790 795 800

Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu

805 810 815

Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys

820 825 830

Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys

835 840 845

Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp

850 855 860

Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr

865 870 875 880

Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala

885 890 895

Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val

900 905 910

Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile

915 920 925

Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys

930 935 940

Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val

945 950 955 960

Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp

965 970 975

Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg

980 985 990

Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln

995 1000 1005

Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala

1010 1015 1020

Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp

1025 1030 1035

Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala

1040 1045 1050

Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln

1055 1060 1065

Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys

1070 1075 1080

Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His

1085 1090 1095

Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr

1100 1105 1110

Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly

1115 1120 1125

Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp

1130 1135 1140

Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser

1145 1150 1155

Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val

1160 1165 1170

Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1175 1180 1185

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr

1190 1195 1200

Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile

1205 1210 1215

Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys

1220 1225 1230

Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly

1235 1240 1245

Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys

1250 1255 1260

Gly Val Lys Leu His Tyr Thr

1265 1270

<210> 45

<211> 1273

<212> PRT

<213> SARS-CoV-2

<400> 45

Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val

1 5 10 15

Asn Phe Thr Asn Arg Thr Gln Leu Pro Ser Ala Tyr Thr Asn Ser Phe

20 25 30

Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu

35 40 45

His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp

50 55 60

Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp

65 70 75 80

Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu

85 90 95

Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser

100 105 110

Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile

115 120 125

Lys Val Cys Glu Phe Gln Phe Cys Asn Tyr Pro Phe Leu Gly Val Tyr

130 135 140

Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr

145 150 155 160

Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu

165 170 175

Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Ser Glu Phe

180 185 190

Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr

195 200 205

Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu

210 215 220

Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr

225 230 235 240

Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser

245 250 255

Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro

260 265 270

Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala

275 280 285

Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys

290 295 300

Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val

305 310 315 320

Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys

325 330 335

Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala

340 345 350

Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu

355 360 365

Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro

370 375 380

Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe

385 390 395 400

Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly

405 410 415

Thr Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys

420 425 430

Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn

435 440 445

Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe

450 455 460

Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys

465 470 475 480

Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly

485 490 495

Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val

500 505 510

Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys

515 520 525

Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn

530 535 540

Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu

545 550 555 560

Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val

565 570 575

Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe

580 585 590

Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val

595 600 605

Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile

610 615 620

His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser

625 630 635 640

Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu Tyr Val

645 650 655

Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala

660 665 670

Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala

675 680 685

Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser

690 695 700

Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile

705 710 715 720

Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val

725 730 735

Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu

740 745 750

Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr

755 760 765

Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln

770 775 780

Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe

785 790 795 800

Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser

805 810 815

Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly

820 825 830

Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp

835 840 845

Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu

850 855 860

Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly

865 870 875 880

Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile

885 890 895

Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr

900 905 910

Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn

915 920 925

Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala

930 935 940

Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn

945 950 955 960

Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val

965 970 975

Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln

980 985 990

Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val

995 1000 1005

Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn

1010 1015 1020

Leu Ala Ala Ile Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys

1025 1030 1035

Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro

1040 1045 1050

Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val

1055 1060 1065

Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His

1070 1075 1080

Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn

1085 1090 1095

Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln

1100 1105 1110

Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val

1115 1120 1125

Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1130 1135 1140

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn

1145 1150 1155

His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn

1160 1165 1170

Ala Ser Phe Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu

1175 1180 1185

Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu

1190 1195 1200

Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu

1205 1210 1215

Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met

1220 1225 1230

Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys

1235 1240 1245

Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro

1250 1255 1260

Val Leu Lys Gly Val Lys Leu His Tyr Thr

1265 1270

<210> 46

<211> 1271

<212> PRT

<213> SARS-CoV-2

<400> 46

Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val

1 5 10 15

Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe

20 25 30

Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu

35 40 45

His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp

50 55 60

Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp

65 70 75 80

Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu

85 90 95

Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser

100 105 110

Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile

115 120 125

Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr

130 135 140

Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser

145 150 155 160

Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp

165 170 175

Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe

180 185 190

Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile

195 200 205

Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu

210 215 220

Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu

225 230 235 240

Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp

245 250 255

Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr

260 265 270

Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp

275 280 285

Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe

290 295 300

Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro

305 310 315 320

Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe

325 330 335

Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn

340 345 350

Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn

355 360 365

Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys

370 375 380

Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile

385 390 395 400

Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile

405 410 415

Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile

420 425 430

Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn

435 440 445

Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg

450 455 460

Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly

465 470 475 480

Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln

485 490 495

Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser

500 505 510

Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser

515 520 525

Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu

530 535 540

Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe

545 550 555 560

Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp

565 570 575

Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly

580 585 590

Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val

595 600 605

Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala

610 615 620

Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val

625 630 635 640

Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn

645 650 655

Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr

660 665 670

Gln Thr Gln Thr Asn Ser Arg Arg Arg Ala Arg Ser Val Ala Ser Gln

675 680 685

Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala

690 695 700

Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val

705 710 715 720

Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys

725 730 735

Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu

740 745 750

Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile

755 760 765

Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys

770 775 780

Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe

785 790 795 800

Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile

805 810 815

Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile

820 825 830

Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile

835 840 845

Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr

850 855 860

Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile

865 870 875 880

Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe

885 890 895

Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn

900 905 910

Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala

915 920 925

Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly

930 935 940

Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu

945 950 955 960

Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn

965 970 975

Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp

980 985 990

Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln

995 1000 1005

Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala

1010 1015 1020

Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val

1025 1030 1035

Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser

1040 1045 1050

Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala

1055 1060 1065

Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly

1070 1075 1080

Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr

1085 1090 1095

His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile

1100 1105 1110

Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile

1115 1120 1125

Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu

1130 1135 1140

Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr

1145 1150 1155

Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1160 1165 1170

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala

1175 1180 1185

Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys

1190 1195 1200

Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe

1205 1210 1215

Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys

1220 1225 1230

Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys

1235 1240 1245

Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu

1250 1255 1260

Lys Gly Val Lys Leu His Tyr Thr

1265 1270

<210> 47

<211> 1273

<212> PRT

<213> SARS-CoV-2

<400> 47

Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ile Gln Cys Val

1 5 10 15

Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe

20 25 30

Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu

35 40 45

His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp

50 55 60

Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp

65 70 75 80

Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu

85 90 95

Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser

100 105 110

Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile

115 120 125

Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr

130 135 140

Tyr His Lys Asn Asn Lys Ser Cys Met Glu Ser Glu Phe Arg Val Tyr

145 150 155 160

Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu

165 170 175

Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe

180 185 190

Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr

195 200 205

Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu

210 215 220

Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr

225 230 235 240

Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser

245 250 255

Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro

260 265 270

Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala

275 280 285

Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys

290 295 300

Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val

305 310 315 320

Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys

325 330 335

Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala

340 345 350

Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu

355 360 365

Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro

370 375 380

Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe

385 390 395 400

Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly

405 410 415

Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys

420 425 430

Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn

435 440 445

Tyr Asn Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe

450 455 460

Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys

465 470 475 480

Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly

485 490 495

Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val

500 505 510

Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys

515 520 525

Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn

530 535 540

Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu

545 550 555 560

Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val

565 570 575

Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe

580 585 590

Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val

595 600 605

Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile

610 615 620

His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser

625 630 635 640

Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val

645 650 655

Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala

660 665 670

Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala

675 680 685

Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser

690 695 700

Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile

705 710 715 720

Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val

725 730 735

Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu

740 745 750

Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr

755 760 765

Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln

770 775 780

Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe

785 790 795 800

Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser

805 810 815

Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly

820 825 830

Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp

835 840 845

Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu

850 855 860

Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly

865 870 875 880

Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile

885 890 895

Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr

900 905 910

Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn

915 920 925

Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala

930 935 940

Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn

945 950 955 960

Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val

965 970 975

Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln

980 985 990

Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val

995 1000 1005

Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn

1010 1015 1020

Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys

1025 1030 1035

Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro

1040 1045 1050

Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val

1055 1060 1065

Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His

1070 1075 1080

Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn

1085 1090 1095

Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln

1100 1105 1110

Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val

1115 1120 1125

Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1130 1135 1140

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn

1145 1150 1155

His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn

1160 1165 1170

Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu

1175 1180 1185

Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu

1190 1195 1200

Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu

1205 1210 1215

Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met

1220 1225 1230

Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys

1235 1240 1245

Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro

1250 1255 1260

Val Leu Lys Gly Val Lys Leu His Tyr Thr

1265 1270

<210> 48

<211> 1270

<212> PRT

<213> SARS-CoV-2

<400> 48

Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val

1 5 10 15

Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe

20 25 30

Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu

35 40 45

His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp

50 55 60

Phe His Val Ile Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro

65 70 75 80

Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu Lys Ser

85 90 95

Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr

100 105 110

Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile Lys Val

115 120 125

Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp His Lys Asn Asn

130 135 140

Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn

145 150 155 160

Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly

165 170 175

Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile

180 185 190

Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Ile Val Arg

195 200 205

Glu Pro Glu Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val

210 215 220

Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala

225 230 235 240

Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr

245 250 255

Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe

260 265 270

Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys

275 280 285

Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr

290 295 300

Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr

305 310 315 320

Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Asp

325 330 335

Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg

340 345 350

Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Leu

355 360 365

Ala Pro Phe Phe Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu

370 375 380

Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg

385 390 395 400

Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile Ala

405 410 415

Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala

420 425 430

Trp Asn Ser Asn Lys Leu Asp Ser Lys Val Ser Gly Asn Tyr Asn Tyr

435 440 445

Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp

450 455 460

Ile Ser Thr Glu Ile Tyr Gln Ala Gly Asn Lys Pro Cys Asn Gly Val

465 470 475 480

Ala Gly Phe Asn Cys Tyr Phe Pro Leu Arg Ser Tyr Ser Phe Arg Pro

485 490 495

Thr Tyr Gly Val Gly His Gln Pro Tyr Arg Val Val Val Leu Ser Phe

500 505 510

Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr

515 520 525

Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Lys

530 535 540

Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln

545 550 555 560

Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro

565 570 575

Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val

580 585 590

Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu

595 600 605

Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp

610 615 620

Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe

625 630 635 640

Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu Tyr Val Asn Asn Ser

645 650 655

Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln

660 665 670

Thr Gln Thr Lys Ser His Arg Arg Ala Arg Ser Val Ala Ser Gln Ser

675 680 685

Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr

690 695 700

Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr

705 710 715 720

Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr

725 730 735

Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln

740 745 750

Tyr Gly Ser Phe Cys Thr Gln Leu Lys Arg Ala Leu Thr Gly Ile Ala

755 760 765

Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln

770 775 780

Ile Tyr Lys Thr Pro Pro Ile Lys Tyr Phe Gly Gly Phe Asn Phe Ser

785 790 795 800

Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu

805 810 815

Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys

820 825 830

Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys

835 840 845

Ala Gln Lys Phe Lys Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp

850 855 860

Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr

865 870 875 880

Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala

885 890 895

Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val

900 905 910

Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile

915 920 925

Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys

930 935 940

Leu Gln Asp Val Val Asn His Asn Ala Gln Ala Leu Asn Thr Leu Val

945 950 955 960

Lys Gln Leu Ser Ser Lys Phe Gly Ala Ile Ser Ser Val Leu Asn Asp

965 970 975

Ile Phe Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg

980 985 990

Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln

995 1000 1005

Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala

1010 1015 1020

Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp

1025 1030 1035

Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala

1040 1045 1050

Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln

1055 1060 1065

Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys

1070 1075 1080

Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His

1085 1090 1095

Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr

1100 1105 1110

Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly

1115 1120 1125

Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp

1130 1135 1140

Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser

1145 1150 1155

Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val

1160 1165 1170

Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1175 1180 1185

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr

1190 1195 1200

Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile

1205 1210 1215

Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys

1220 1225 1230

Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly

1235 1240 1245

Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys

1250 1255 1260

Gly Val Lys Leu His Tyr Thr

1265 1270

<210> 49

<211> 3825

<212> DNA

<213> SARS-CoV-2

<400> 49

atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgaccacc 60

agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120

aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180

aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240

aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300

atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360

aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420

ctgggcgtct actaccacaa gaacaacaag agctggatgg aaagcgagtt ccgggtgtac 480

agcagcgcca acaactgcac cttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540

ggcaagcagg gcaacttcaa gaacctgcgc gagttcgtgt ttaagaacat cgacggctac 600

ttcaagatct acagcaagca cacccctatc aacctcgtgc gggatctgcc tcagggcttc 660

tctgctctgg aacccctggt ggatctgccc atcggcatca acatcacccg gtttcagaca 720

ctgctggccc tgcacagaag ctacctgaca cctggcgata gcagcagcgg atggacagct 780

ggtgccgccg cttactatgt gggctacctg cagcctagaa ccttcctgct gaagtacaac 840

gagaacggca ccatcaccga cgccgtggat tgtgctctgg atcctctgag cgagacaaag 900

tgcaccctga agtccttcac cgtggaaaag ggcatctacc agaccagcaa cttccgggtg 960

cagcccaccg aatccatcgt gcggttcccc aatatcacca atctgtgccc cttcggcgag 1020

gtgttcaatg ccaccagatt cgcctctgtg tacgcctgga accggaagcg gatcagcaat 1080

tgcgtggccg actactccgt gctgtacaac tccgccagct tcagcacctt caagtgctac 1140

ggcgtgtccc ctaccaagct gaacgacctg tgcttcacaa acgtgtacgc cgacagcttc 1200

gtgatccggg gagatgaagt gcggcagatt gcccctggac agacaggcaa gatcgccgac 1260

tacaactaca agctgcccga cgacttcacc ggctgtgtga ttgcctggaa cagcaacaac 1320

ctggactcca aagtcggcgg caactacaat tacctgtacc ggctgttccg gaagtccaat 1380

ctgaagccct tcgagcggga catctccacc gagatctatc aggccggcag caccccttgt 1440

aacggcgtgg aaggcttcaa ctgctacttc ccactgcagt cctacggctt tcagcccaca 1500

aatggcgtgg gctatcagcc ctacagagtg gtggtgctga gcttcgaact gctgcatgcc 1560

cctgccacag tgtgcggccc taagaaaagc accaatctcg tgaagaacaa atgcgtgaac 1620

ttcaacttca acggcctgac cggcaccggc gtgctgacag agagcaacaa gaagttcctg 1680

ccattccagc agtttggccg ggatatcgcc gataccacag acgccgttag agatccccag 1740

acactggaaa tcctggacat caccccttgc agcttcggcg gagtgtctgt gatcacccct 1800

ggcaccaaca ccagcaatca ggtggcagtg ctgtaccagg acgtgaactg taccgaagtg 1860

cccgtggcca ttcacgccga tcagctgaca cctacatggc gggtgtactc caccggcagc 1920

aatgtgtttc agaccagagc cggctgtctg atcggagccg agcacgtgaa caatagctac 1980

gagtgcgaca tccccatcgg cgctggaatc tgcgccagct accagacaca gacaaacagc 2040

cctcggagag ccagaagcgt ggccagccag agcatcattg cctacacaat gtctctgggc 2100

gccgagaaca gcgtggccta ctccaacaac tctatcgcta tccccaccaa cttcaccatc 2160

agcgtgacca cagagatcct gcctgtgtcc atgaccaaga ccagcgtgga ctgcaccatg 2220

tacatctgcg gcgattccac cgagtgctcc aacctgctgc tgcagtacgg cagcttctgc 2280

acccagctga atagagccct gacagggatc gccgtggaac aggacaagaa cacccaagag 2340

gtgttcgccc aagtgaagca gatctacaag acccctccta tcaaggactt cggcggcttc 2400

aatttcagcc agattctgcc cgatcctagc aagcccagca agcggagctt catcgaggac 2460

ctgctgttca acaaagtgac actggccgac gccggcttca tcaagcagta tggcgattgt 2520

ctgggcgaca ttgccgccag ggatctgatt tgcgcccaga agtttaacgg actgacagtg 2580

ctgcctcctc tgctgaccga tgagatgatc gcccagtaca catctgccct gctggccggc 2640

acaatcacaa gcggctggac atttggagca ggcgccgctc tgcagatccc ctttgctatg 2700

cagatggcct accggttcaa cggcatcgga gtgacccaga atgtgctgta cgagaaccag 2760

aagctgatcg ccaaccagtt caacagcgcc atcggcaaga tccaggacag cctgagcagc 2820

acagcaagcg ccctgggaaa gctgcaggac gtggtcaacc agaatgccca ggcactgaac 2880

accctggtca agcagctgtc ctccaacttc ggcgccatca gctctgtgct gaacgatatc 2940

ctgagcagac tggaccctcc tgaggccgag gtgcagatcg acagactgat cacaggcaga 3000

ctgcagagcc tccagacata cgtgacccag cagctgatca gagccgccga gattagagcc 3060

tctgccaatc tggccgccac caagatgtct gagtgtgtgc tgggccagag caagagagtg 3120

gacttttgcg gcaagggcta ccacctgatg agcttccctc agtctgcccc tcacggcgtg 3180

gtgtttctgc acgtgacata tgtgcccgct caagagaaga atttcaccac cgctccagcc 3240

atctgccacg acggcaaagc ccactttcct agagaaggcg tgttcgtgtc caacggcacc 3300

cattggttcg tgacacagcg gaacttctac gagccccaga tcatcaccac cgacaacacc 3360

ttcgtgtctg gcaactgcga cgtcgtgatc ggcattgtga acaataccgt gtacgaccct 3420

ctgcagcccg agctggacag cttcaaagag gaactggaca agtactttaa gaaccacaca 3480

agccccgacg tggacctggg cgatatcagc ggaatcaatg ccagcgtcgt gaacatccag 3540

aaagagatcg accggctgaa cgaggtggcc aagaatctga acgagagcct gatcgacctg 3600

caagaactgg ggaagtacga gcagtacatc aagtggccct ggtacatctg gctgggcttt 3660

atcgccggac tgattgccat cgtgatggtc acaatcatgc tgtgttgcat gaccagctgc 3720

tgtagctgcc tgaagggctg ttgtagctgt ggcagctgct gcaagttcga cgaggacgat 3780

tctgagcccg tgctgaaggg cgtgaaactg cactacacat gatga 3825

<210> 50

<211> 3816

<212> DNA

<213> SARS-CoV-2

<400> 50

atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgaccacc 60

agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120

aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180

aacgtgacct ggttccacgc catctccggc accaatggca ccaagagatt cgacaacccc 240

gtgctgccct tcaacgacgg ggtgtacttt gccagcaccg agaagtccaa catcatcaga 300

ggctggatct tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac 360

gccaccaacg tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctgggc 420

gtctaccaca agaacaacaa gagctggatg gaaagcgagt tccgggtgta cagcagcgcc 480

aacaactgca ccttcgagta cgtgtcccag cctttcctga tggacctgga aggcaagcag 540

ggcaacttca agaacctgcg cgagttcgtg tttaagaaca tcgacggcta cttcaagatc 600

tacagcaagc acacccctat caacctcgtg cgggatctgc ctcagggctt ctctgctctg 660

gaacccctgg tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc 720

ctgcacagaa gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc 780

gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840

accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900

aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960

gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttcggcga ggtgttcaat 1020

gccaccagat tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc 1080

gactactccg tgctgtacaa ctccgccagc ttcagcacct tcaagtgcta cggcgtgtcc 1140

cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg 1200

ggagatgaag tgcggcagat tgcccctgga cagacaggca agatcgccga ctacaactac 1260

aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa cctggactcc 1320

aaagtcggcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa tctgaagccc 1380

ttcgagcggg acatctccac cgagatctat caggccggca gcaccccttg taacggcgtg 1440

gaaggcttca actgctactt cccactgcag tcctacggct ttcagcccac atacggcgtg 1500

ggctatcagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca 1560

gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc 1620

aacggcctga ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag 1680

cagtttggcc gggatatcga cgataccaca gacgccgtta gagatcccca gacactggaa 1740

atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac 1800

accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc 1860

attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt 1920

cagaccagag ccggctgtct gatcggagcc gagcacgtga acaatagcta cgagtgcgac 1980

atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaacag ccaccggaga 2040

gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac 2100

agcgtggcct actccaacaa ctctatcgct atccccatca acttcaccat cagcgtgacc 2160

acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc 2220

ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg 2280

aatagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc 2340

caagtgaagc agatctacaa gacccctcct atcaaggact tcggcggctt caatttcagc 2400

cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc 2460

aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac 2520

attgccgcca gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct 2580

ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca 2640

agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc 2700

taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc 2760

gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc 2820

gccctgggaa agctgcagga cgtggtcaac cagaatgccc aggcactgaa caccctggtc 2880

aagcagctgt cctccaactt cggcgccatc agctctgtgc tgaacgatat cctggcaaga 2940

ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc 3000

ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat 3060

ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc 3120

ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg 3180

cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac 3240

gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc 3300

gtgacacagc ggaacttcta cgagccccag atcatcacca cccacaacac cttcgtgtct 3360

ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc 3420

gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac 3480

gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc 3540

gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg 3600

gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga 3660

ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc 3720

ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc 3780

gtgctgaagg gcgtgaaact gcactacaca tgatga 3816

<210> 51

<211> 3816

<212> DNA

<213> SARS-CoV-2

<400> 51

atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cttcaccacc 60

agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120

aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180

aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgcc 240

aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300

atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360

aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420

ctgggcgtct actaccacaa gaacaacaag agctggatgg aaagcgagtt ccgggtgtac 480

agcagcgcca acaactgcac cttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540

ggcaagcagg gcaacttcaa gaacctgcgc gagttcgtgt ttaagaacat cgacggctac 600

ttcaagatct acagcaagca cacccctatc aacctcgtgc ggggtctgcc tcagggcttc 660

tctgctctgg aacccctggt ggatctgccc atcggcatca acatcacccg gtttcagaca 720

ctgcacagaa gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc 780

gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840

accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900

aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960

gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttcggcga ggtgttcaat 1020

gccaccagat tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc 1080

gactactccg tgctgtacaa ctccgccagc ttcagcacct tcaagtgcta cggcgtgtcc 1140

cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg 1200

ggagatgaag tgcggcagat tgcccctgga cagacaggca atatcgccga ctacaactac 1260

aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa cctggactcc 1320

aaagtcggcg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa tctgaagccc 1380

ttcgagcggg acatctccac cgagatctat caggccggca gcaccccttg taacggcgtg 1440

aaaggcttca actgctactt cccactgcag tcctacggct ttcagcccac atacggcgtg 1500

ggctatcagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca 1560

gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc 1620

aacggcctga ccggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag 1680

cagtttggcc gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa 1740

atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac 1800

accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc 1860

attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt 1920

cagaccagag ccggctgtct gatcggagcc gagcacgtga acaatagcta cgagtgcgac 1980

atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaacag ccctcggaga 2040

gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgtggagaac 2100

agcgtggcct actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc 2160

acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc 2220

ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg 2280

aatagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc 2340

caagtgaagc agatctacaa gacccctcct atcaaggact tcggcggctt caatttcagc 2400

cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc 2460

aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac 2520

attgccgcca gggatctgat ttgcgcccag aagtttaacg gactgacagt gctgcctcct 2580

ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca 2640

agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc 2700

taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc 2760

gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc 2820

gccctgggaa agctgcagga cgtggtcaac cagaatgccc aggcactgaa caccctggtc 2880

aagcagctgt cctccaactt cggcgccatc agctctgtgc tgaacgatat cctgagcaga 2940

ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc 3000

ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat 3060

ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc 3120

ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg 3180

cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac 3240

gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc 3300

gtgacacagc ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct 3360

ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc 3420

gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac 3480

gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc 3540

gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg 3600

gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga 3660

ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc 3720

ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc 3780

gtgctgaagg gcgtgaaact gcactacaca tgatga 3816

<210> 52

<211> 3825

<212> DNA

<213> SARS-CoV-2

<400> 52

atgttcgtgt tcctggtgct gctgcccctg gtgagctccc agtgcgtgaa ctttacaaac 60

agaacacagc tgccctccgc ctacacaaac agcttcacca ggggcgtgta ctaccccgat 120

aaggtctttc ggtccagcgt gctgcacagc acccaggatc tgttcctgcc tttcttcagc 180

aacgtgacat ggtttcacgc catccacgtg agcgggacaa acggcaccaa gcggttcgat 240

aacccagtgc tgccctttaa cgatggggtg tacttcgcca gcacagagaa gtccaacatc 300

atcaggggct ggattttcgg caccaccctc gattccaaga cacagtccct gctgatcgtg 360

aacaacgcca caaacgtggt cattaaggtg tgcgagttcc agttttgcaa ctacccattc 420

ctgggcgtgt actaccacaa gaacaacaag tcctggatgg agagcgagtt cagggtctac 480

tcctccgcca acaactgcac cttcgagtac gtgagccagc ccttcctgat ggatctggag 540

ggcaagcagg ggaacttcaa gaacctgagc gagttcgtgt tcaagaacat tgacggctac 600

tttaagatct acagtaagca cacacctatc aacctggtgc gggacctgcc tcagggcttc 660

tccgccctcg agccactggt ggatctgcca atcggcatta acatcaccag gttccagaca 720

ctgctggccc tgcacaggag ctacctgact ccaggcgata gctccagcgg gtggacagcc 780

ggggccgccg cctactacgt gggctacctg cagcccagaa cctttctgct gaagtacaac 840

gagaacggga ccatcaccga tgccgtggat tgcgccctgg accccctgag cgagaccaag 900

tgcactctca agtccttcac cgtggagaag ggcatctacc agaccagcaa cttccgggtc 960

cagcccacag agtccatcgt gaggttcccc aacatcacca acctctgccc cttcggcgag 1020

gtgttcaacg ccaccaggtt tgccagcgtg tacgcctgga acaggaagag gatctccaac 1080

tgcgtggccg attacagcgt gctgtacaac tccgcctcct tcagcacctt caagtgctac 1140

ggcgtgagcc ctaccaagct taacgatctg tgctttacaa acgtgtacgc cgatagcttt 1200

gtgatccggg gggacgaggt gaggcagatt gcccccggcc agacagggac catcgccgat 1260

tacaactaca agctgcccga tgacttcacc gggtgcgtga ttgcctggaa cagcaacaac 1320

ctcgatagca aggtcggggg gaactacaac tacctgtaca ggctgtttag aaagtccaac 1380

ctcaagcctt tcgagcggga tattagcact gagatctacc aggccgggag cacaccctgc 1440

aacggggtga agggcttcaa ctgctacttt cccctgcaga gctacggctt ccagccaaca 1500

tacggcgtgg ggtaccagcc ctaccgggtg gtggtgctga gcttcgagct gctgcacgcc 1560

cctgccaccg tgtgcggccc caagaaaagc actaacctgg tgaagaacaa gtgcgtcaac 1620

ttcaacttta acggcctgac cggcacaggg gtgctgaccg agtccaacaa gaagttcctg 1680

cccttccagc agttcggccg ggacatcgcc gataccactg acgccgtgag ggacccccag 1740

accctggaga tcctggacat tacaccctgt agcttcggcg gggtcagcgt gatcacaccc 1800

ggcaccaaca catccaacca ggtggccgtg ctgtaccagg gcgtgaactg caccgaggtg 1860

cccgtcgcca tccacgccga ccagctgaca cccacatgga gggtgtacag cacagggagc 1920

aacgtgttcc agaccagggc cgggtgcctg atcggcgccg agtacgtgaa caactcctac 1980

gagtgcgaca tccccatcgg ggccggcatt tgcgcctcct accagaccca gaccaacagc 2040

ccccggcggg ccaggagcgt ggccagccag agcatcattg cctacacaat gtctctgggc 2100

gccgagaaca gcgtggccta ctccaacaac tctatcgcta tccccaccaa cttcaccatc 2160

agcgtgacca cagagatcct gcctgtgtcc atgaccaaga ccagcgtgga ctgcaccatg 2220

tacatctgcg gcgattccac cgagtgctcc aacctgctgc tgcagtacgg cagcttctgc 2280

acccagctga atagagccct gacagggatc gccgtggaac aggacaagaa cacccaagag 2340

gtgttcgccc aagtgaagca gatctacaag acccctccta tcaaggactt cggcggcttc 2400

aatttcagcc agattctgcc cgatcctagc aagcccagca agcggagctt catcgaggac 2460

ctgctgttca acaaagtgac actggccgac gccggcttca tcaagcagta tggcgattgt 2520

ctgggcgaca ttgccgccag ggatctgatt tgcgcccaga agtttaacgg actgacagtg 2580

ctgcctcctc tgctgaccga tgagatgatc gcccagtaca catctgccct gctggccggc 2640

acaatcacaa gcggctggac atttggagca ggcgccgctc tgcagatccc ctttgctatg 2700

cagatggcct accggttcaa cggcatcgga gtgacccaga atgtgctgta cgagaaccag 2760

aagctgatcg ccaaccagtt caacagcgcc atcggcaaga tccaggacag cctgagcagc 2820

acagcaagcg ccctgggaaa gctgcaggac gtggtcaacc agaatgccca ggcactgaac 2880

accctggtca agcagctgtc ctccaacttc ggcgccatca gctctgtgct gaacgatatc 2940

ctgagcagac tggaccctcc tgaggccgag gtgcagatcg acagactgat cacaggcaga 3000

ctgcagagcc tccagacata cgtgacccag cagctgatca gagccgccga gattagagcc 3060

tctgccaatc tggccgccat caagatgtct gagtgtgtgc tgggccagag caagagagtg 3120

gacttttgcg gcaagggcta ccacctgatg agcttccctc agtctgcccc tcacggcgtg 3180

gtgtttctgc acgtgacata tgtgcccgct caagagaaga atttcaccac cgctccagcc 3240

atctgccacg acggcaaagc ccactttcct agagaaggcg tgttcgtgtc caacggcacc 3300

cattggttcg tgacacagcg gaacttctac gagccccaga tcatcaccac cgacaacacc 3360

ttcgtgtctg gcaactgcga cgtcgtgatc ggcattgtga acaataccgt gtacgaccct 3420

ctgcagcccg agctggacag cttcaaagag gaactggaca agtactttaa gaaccacaca 3480

agccccgacg tggacctggg cgatatcagc ggaatcaatg ccagcttcgt gaacatccag 3540

aaagagatcg accggctgaa cgaggtggcc aagaatctga acgagagcct gatcgacctg 3600

caagaactgg ggaagtacga gcagtacatc aagtggccct ggtacatctg gctgggcttt 3660

atcgccggac tgattgccat cgtgatggtc acaatcatgc tgtgttgcat gaccagctgc 3720

tgtagctgcc tgaagggctg ttgtagctgt ggcagctgct gcaagttcga cgaggacgat 3780

tctgagcccg tgctgaaggg cgtgaaactg cactacacat gatga 3825

<210> 53

<211> 3819

<212> DNA

<213> SARS-CoV-2

<400> 53

atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgagaacc 60

agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120

aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180

aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240

aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300

atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360

aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420

ctggacgtct actaccacaa gaacaacaag agctggatgg aaagcggcgt gtacagcagc 480

gccaacaact gcaccttcga gtacgtgtcc cagcctttcc tgatggacct ggaaggcaag 540

cagggcaact tcaagaacct gcgcgagttc gtgtttaaga acatcgacgg ctacttcaag 600

atctacagca agcacacccc tatcaacctc gtgcgggatc tgcctcaggg cttctctgct 660

ctggaacccc tggtggatct gcccatcggc atcaacatca cccggtttca gacactgctg 720

gccctgcaca gaagctacct gacacctggc gatagcagca gcggatggac agctggtgcc 780

gccgcttact atgtgggcta cctgcagcct agaaccttcc tgctgaagta caacgagaac 840

ggcaccatca ccgacgccgt ggattgtgct ctggatcctc tgagcgagac aaagtgcacc 900

ctgaagtcct tcaccgtgga aaagggcatc taccagacca gcaacttccg ggtgcagccc 960

accgaatcca tcgtgcggtt ccccaatatc accaatctgt gccccttcgg cgaggtgttc 1020

aatgccacca gattcgcctc tgtgtacgcc tggaaccgga agcggatcag caattgcgtg 1080

gccgactact ccgtgctgta caactccgcc agcttcagca ccttcaagtg ctacggcgtg 1140

tcccctacca agctgaacga cctgtgcttc acaaacgtgt acgccgacag cttcgtgatc 1200

cggggagatg aagtgcggca gattgcccct ggacagacag gcaagatcgc cgactacaac 1260

tacaagctgc ccgacgactt caccggctgt gtgattgcct ggaacagcaa caacctggac 1320

tccaaagtcg gcggcaacta caattaccgg taccggctgt tccggaagtc caatctgaag 1380

cccttcgagc gggacatctc caccgagatc tatcaggccg gcagcaagcc ttgtaacggc 1440

gtggaaggct tcaactgcta cttcccactg cagtcctacg gctttcagcc cacaaatggc 1500

gtgggctatc agccctacag agtggtggtg ctgagcttcg aactgctgca tgcccctgcc 1560

acagtgtgcg gccctaagaa aagcaccaat ctcgtgaaga acaaatgcgt gaacttcaac 1620

ttcaacggcc tgaccggcac cggcgtgctg acagagagca acaagaagtt cctgccattc 1680

cagcagtttg gccgggatat cgccgatacc acagacgccg ttagagatcc ccagacactg 1740

gaaatcctgg acatcacccc ttgcagcttc ggcggagtgt ctgtgatcac ccctggcacc 1800

aacaccagca atcaggtggc agtgctgtac cagggcgtga actgtaccga agtgcccgtg 1860

gccattcacg ccgatcagct gacacctaca tggcgggtgt actccaccgg cagcaatgtg 1920

tttcagacca gagccggctg tctgatcgga gccgagcacg tgaacaatag ctacgagtgc 1980

gacatcccca tcggcgctgg aatctgcgcc agctaccaga cacagacaaa cagccggcgg 2040

agagccagaa gcgtggccag ccagagcatc attgcctaca caatgtctct gggcgccgag 2100

aacagcgtgg cctactccaa caactctatc gctatcccca ccaacttcac catcagcgtg 2160

accacagaga tcctgcctgt gtccatgacc aagaccagcg tggactgcac catgtacatc 2220

tgcggcgatt ccaccgagtg ctccaacctg ctgctgcagt acggcagctt ctgcacccag 2280

ctgaatagag ccctgacagg gatcgccgtg gaacaggaca agaacaccca agaggtgttc 2340

gcccaagtga agcagatcta caagacccct cctatcaagg acttcggcgg cttcaatttc 2400

agccagattc tgcccgatcc tagcaagccc agcaagcgga gcttcatcga ggacctgctg 2460

ttcaacaaag tgacactggc cgacgccggc ttcatcaagc agtatggcga ttgtctgggc 2520

gacattgccg ccagggatct gatttgcgcc cagaagttta acggactgac agtgctgcct 2580

cctctgctga ccgatgagat gatcgcccag tacacatctg ccctgctggc cggcacaatc 2640

acaagcggct ggacatttgg agcaggcgcc gctctgcaga tcccctttgc tatgcagatg 2700

gcctaccggt tcaacggcat cggagtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760

atcgccaacc agttcaacag cgccatcggc aagatccagg acagcctgag cagcacagca 2820

agcgccctgg gaaagctgca gaacgtggtc aaccagaatg cccaggcact gaacaccctg 2880

gtcaagcagc tgtcctccaa cttcggcgcc atcagctctg tgctgaacga tatcctgagc 2940

agactggacc ctcctgaggc cgaggtgcag atcgacagac tgatcacagg cagactgcag 3000

agcctccaga catacgtgac ccagcagctg atcagagccg ccgagattag agcctctgcc 3060

aatctggccg ccaccaagat gtctgagtgt gtgctgggcc agagcaagag agtggacttt 3120

tgcggcaagg gctaccacct gatgagcttc cctcagtctg cccctcacgg cgtggtgttt 3180

ctgcacgtga catatgtgcc cgctcaagag aagaatttca ccaccgctcc agccatctgc 3240

cacgacggca aagcccactt tcctagagaa ggcgtgttcg tgtccaacgg cacccattgg 3300

ttcgtgacac agcggaactt ctacgagccc cagatcatca ccaccgacaa caccttcgtg 3360

tctggcaact gcgacgtcgt gatcggcatt gtgaacaata ccgtgtacga ccctctgcag 3420

cccgagctgg acagcttcaa agaggaactg gacaagtact ttaagaacca cacaagcccc 3480

gacgtggacc tgggcgatat cagcggaatc aatgccagcg tcgtgaacat ccagaaagag 3540

atcgaccggc tgaacgaggt ggccaagaat ctgaacgaga gcctgatcga cctgcaagaa 3600

ctggggaagt acgagcagta catcaagtgg ccctggtaca tctggctggg ctttatcgcc 3660

ggactgattg ccatcgtgat ggtcacaatc atgctgtgtt gcatgaccag ctgctgtagc 3720

tgcctgaagg gctgttgtag ctgtggcagc tgctgcaagt tcgacgagga cgattctgag 3780

cccgtgctga agggcgtgaa actgcactac acatgatga 3819

<210> 54

<211> 3825

<212> DNA

<213> SARS-CoV-2

<400> 54

atgttcgtgt tcctggtgct gctgcctctg gtgtccatcc agtgtgtgaa cctgaccacc 60

agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120

aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180

aacgtgacct ggttccacgc catccacgtg tccggcacca atggcaccaa gagattcgac 240

aaccccgtgc tgcccttcaa cgacggggtg tactttgcca gcaccgagaa gtccaacatc 300

atcagaggct ggatcttcgg caccacactg gacagcaaga cccagagcct gctgatcgtg 360

aacaacgcca ccaacgtggt catcaaagtg tgcgagttcc agttctgcaa cgaccccttc 420

ctgggcgtct actaccacaa gaacaacaag agctgcatgg aaagcgagtt ccgggtgtac 480

agcagcgcca acaactgcac cttcgagtac gtgtcccagc ctttcctgat ggacctggaa 540

ggcaagcagg gcaacttcaa gaacctgcgc gagttcgtgt ttaagaacat cgacggctac 600

ttcaagatct acagcaagca cacccctatc aacctcgtgc gggatctgcc tcagggcttc 660

tctgctctgg aacccctggt ggatctgccc atcggcatca acatcacccg gtttcagaca 720

ctgctggccc tgcacagaag ctacctgaca cctggcgata gcagcagcgg atggacagct 780

ggtgccgccg cttactatgt gggctacctg cagcctagaa ccttcctgct gaagtacaac 840

gagaacggca ccatcaccga cgccgtggat tgtgctctgg atcctctgag cgagacaaag 900

tgcaccctga agtccttcac cgtggaaaag ggcatctacc agaccagcaa cttccgggtg 960

cagcccaccg aatccatcgt gcggttcccc aatatcacca atctgtgccc cttcggcgag 1020

gtgttcaatg ccaccagatt cgcctctgtg tacgcctgga accggaagcg gatcagcaat 1080

tgcgtggccg actactccgt gctgtacaac tccgccagct tcagcacctt caagtgctac 1140

ggcgtgtccc ctaccaagct gaacgacctg tgcttcacaa acgtgtacgc cgacagcttc 1200

gtgatccggg gagatgaagt gcggcagatt gcccctggac agacaggcaa gatcgccgac 1260

tacaactaca agctgcccga cgacttcacc ggctgtgtga ttgcctggaa cagcaacaac 1320

ctggactcca aagtcggcgg caactacaat taccgctacc ggctgttccg gaagtccaat 1380

ctgaagccct tcgagcggga catctccacc gagatctatc aggccggcag caccccttgt 1440

aacggcgtgg aaggcttcaa ctgctacttc ccactgcagt cctacggctt tcagcccaca 1500

aatggcgtgg gctatcagcc ctacagagtg gtggtgctga gcttcgaact gctgcatgcc 1560

cctgccacag tgtgcggccc taagaaaagc accaatctcg tgaagaacaa atgcgtgaac 1620

ttcaacttca acggcctgac cggcaccggc gtgctgacag agagcaacaa gaagttcctg 1680

ccattccagc agtttggccg ggatatcgcc gataccacag acgccgttag agatccccag 1740

acactggaaa tcctggacat caccccttgc agcttcggcg gagtgtctgt gatcacccct 1800

ggcaccaaca ccagcaatca ggtggcagtg ctgtaccagg gcgtgaactg taccgaagtg 1860

cccgtggcca ttcacgccga tcagctgaca cctacatggc gggtgtactc caccggcagc 1920

aatgtgtttc agaccagagc cggctgtctg atcggagccg agcacgtgaa caatagctac 1980

gagtgcgaca tccccatcgg cgctggaatc tgcgccagct accagacaca gacaaacagc 2040

cctcggagag ccagaagcgt ggccagccag agcatcattg cctacacaat gtctctgggc 2100

gccgagaaca gcgtggccta ctccaacaac tctatcgcta tccccaccaa cttcaccatc 2160

agcgtgacca cagagatcct gcctgtgtcc atgaccaaga ccagcgtgga ctgcaccatg 2220

tacatctgcg gcgattccac cgagtgctcc aacctgctgc tgcagtacgg cagcttctgc 2280

acccagctga atagagccct gacagggatc gccgtggaac aggacaagaa cacccaagag 2340

gtgttcgccc aagtgaagca gatctacaag acccctccta tcaaggactt cggcggcttc 2400

aatttcagcc agattctgcc cgatcctagc aagcccagca agcggagctt catcgaggac 2460

ctgctgttca acaaagtgac actggccgac gccggcttca tcaagcagta tggcgattgt 2520

ctgggcgaca ttgccgccag ggatctgatt tgcgcccaga agtttaacgg actgacagtg 2580

ctgcctcctc tgctgaccga tgagatgatc gcccagtaca catctgccct gctggccggc 2640

acaatcacaa gcggctggac atttggagca ggcgccgctc tgcagatccc ctttgctatg 2700

cagatggcct accggttcaa cggcatcgga gtgacccaga atgtgctgta cgagaaccag 2760

aagctgatcg ccaaccagtt caacagcgcc atcggcaaga tccaggacag cctgagcagc 2820

acagcaagcg ccctgggaaa gctgcaggac gtggtcaacc agaatgccca ggcactgaac 2880

accctggtca agcagctgtc ctccaacttc ggcgccatca gctctgtgct gaacgatatc 2940

ctgagcagac tggaccctcc tgaggccgag gtgcagatcg acagactgat cacaggcaga 3000

ctgcagagcc tccagacata cgtgacccag cagctgatca gagccgccga gattagagcc 3060

tctgccaatc tggccgccac caagatgtct gagtgtgtgc tgggccagag caagagagtg 3120

gacttttgcg gcaagggcta ccacctgatg agcttccctc agtctgcccc tcacggcgtg 3180

gtgtttctgc acgtgacata tgtgcccgct caagagaaga atttcaccac cgctccagcc 3240

atctgccacg acggcaaagc ccactttcct agagaaggcg tgttcgtgtc caacggcacc 3300

cattggttcg tgacacagcg gaacttctac gagccccaga tcatcaccac cgacaacacc 3360

ttcgtgtctg gcaactgcga cgtcgtgatc ggcattgtga acaataccgt gtacgaccct 3420

ctgcagcccg agctggacag cttcaaagag gaactggaca agtactttaa gaaccacaca 3480

agccccgacg tggacctggg cgatatcagc ggaatcaatg ccagcgtcgt gaacatccag 3540

aaagagatcg accggctgaa cgaggtggcc aagaatctga acgagagcct gatcgacctg 3600

caagaactgg ggaagtacga gcagtacatc aagtggccct ggtacatctg gctgggcttt 3660

atcgccggac tgattgccat cgtgatggtc acaatcatgc tgtgttgcat gaccagctgc 3720

tgtagctgcc tgaagggctg ttgtagctgt ggcagctgct gcaagttcga cgaggacgat 3780

tctgagcccg tgctgaaggg cgtgaaactg cactacacat gatga 3825

<210> 55

<211> 3816

<212> DNA

<213> SARS-CoV-2

<400> 55

atgttcgtgt tcctggtgct gctgcctctg gtgtccagcc agtgtgtgaa cctgaccacc 60

agaacacagc tgcctccagc ctacaccaac agctttacca gaggcgtgta ctaccccgac 120

aaggtgttca gatccagcgt gctgcactct acccaggacc tgttcctgcc tttcttcagc 180

aacgtgacct ggttccacgt gatctccggc accaatggca ccaagagatt cgacaacccc 240

gtgctgccct tcaacgacgg ggtgtacttt gccagcatcg agaagtccaa catcatcaga 300

ggctggatct tcggcaccac actggacagc aagacccaga gcctgctgat cgtgaacaac 360

gccaccaacg tggtcatcaa agtgtgcgag ttccagttct gcaacgaccc cttcctggac 420

cacaagaaca acaagagctg gatggaaagc gagttccggg tgtacagcag cgccaacaac 480

tgcaccttcg agtacgtgtc ccagcctttc ctgatggacc tggaaggcaa gcagggcaac 540

ttcaagaacc tgcgcgagtt cgtgtttaag aacatcgacg gctacttcaa gatctacagc 600

aagcacaccc ctatcatcgt gcgggaacct gaagatctgc ctcagggctt ctctgctctg 660

gaacccctgg tggatctgcc catcggcatc aacatcaccc ggtttcagac actgctggcc 720

ctgcacagaa gctacctgac acctggcgat agcagcagcg gatggacagc tggtgccgcc 780

gcttactatg tgggctacct gcagcctaga accttcctgc tgaagtacaa cgagaacggc 840

accatcaccg acgccgtgga ttgtgctctg gatcctctga gcgagacaaa gtgcaccctg 900

aagtccttca ccgtggaaaa gggcatctac cagaccagca acttccgggt gcagcccacc 960

gaatccatcg tgcggttccc caatatcacc aatctgtgcc ccttcgacga ggtgttcaat 1020

gccaccagat tcgcctctgt gtacgcctgg aaccggaagc ggatcagcaa ttgcgtggcc 1080

gactactccg tgctgtacaa cctggccccc ttcttcacct tcaagtgcta cggcgtgtcc 1140

cctaccaagc tgaacgacct gtgcttcaca aacgtgtacg ccgacagctt cgtgatccgg 1200

ggagatgaag tgcggcagat tgcccctgga cagacaggca acatcgccga ctacaactac 1260

aagctgcccg acgacttcac cggctgtgtg attgcctgga acagcaacaa gctggactcc 1320

aaagtctccg gcaactacaa ttacctgtac cggctgttcc ggaagtccaa tctgaagccc 1380

ttcgagcggg acatctccac cgagatctat caggccggca acaagccttg taacggcgtg 1440

gccggcttca actgctactt cccactgcgg tcctactcct ttcggcccac atatggcgtg 1500

ggccatcagc cctacagagt ggtggtgctg agcttcgaac tgctgcatgc ccctgccaca 1560

gtgtgcggcc ctaagaaaag caccaatctc gtgaagaaca aatgcgtgaa cttcaacttc 1620

aacggcctga agggcaccgg cgtgctgaca gagagcaaca agaagttcct gccattccag 1680

cagtttggcc gggatatcgc cgataccaca gacgccgtta gagatcccca gacactggaa 1740

atcctggaca tcaccccttg cagcttcggc ggagtgtctg tgatcacccc tggcaccaac 1800

accagcaatc aggtggcagt gctgtaccag ggcgtgaact gtaccgaagt gcccgtggcc 1860

attcacgccg atcagctgac acctacatgg cgggtgtact ccaccggcag caatgtgttt 1920

cagaccagag ccggctgtct gatcggagcc gagtacgtga acaatagcta cgagtgcgac 1980

atccccatcg gcgctggaat ctgcgccagc taccagacac agacaaagag ccatcggaga 2040

gccagaagcg tggccagcca gagcatcatt gcctacacaa tgtctctggg cgccgagaac 2100

agcgtggcct actccaacaa ctctatcgct atccccacca acttcaccat cagcgtgacc 2160

acagagatcc tgcctgtgtc catgaccaag accagcgtgg actgcaccat gtacatctgc 2220

ggcgattcca ccgagtgctc caacctgctg ctgcagtacg gcagcttctg cacccagctg 2280

aagagagccc tgacagggat cgccgtggaa caggacaaga acacccaaga ggtgttcgcc 2340

caagtgaagc agatctacaa gacccctcct atcaagtact tcggcggctt caatttcagc 2400

cagattctgc ccgatcctag caagcccagc aagcggagct tcatcgagga cctgctgttc 2460

aacaaagtga cactggccga cgccggcttc atcaagcagt atggcgattg tctgggcgac 2520

attgccgcca gggatctgat ttgcgcccag aagtttaagg gactgacagt gctgcctcct 2580

ctgctgaccg atgagatgat cgcccagtac acatctgccc tgctggccgg cacaatcaca 2640

agcggctgga catttggagc aggcgccgct ctgcagatcc cctttgctat gcagatggcc 2700

taccggttca acggcatcgg agtgacccag aatgtgctgt acgagaacca gaagctgatc 2760

gccaaccagt tcaacagcgc catcggcaag atccaggaca gcctgagcag cacagcaagc 2820

gccctgggaa agctgcagga cgtggtcaac cacaatgccc aggcactgaa caccctggtc 2880

aagcagctgt cctccaagtt cggcgccatc agctctgtgc tgaacgatat cttcagcaga 2940

ctggaccctc ctgaggccga ggtgcagatc gacagactga tcacaggcag actgcagagc 3000

ctccagacat acgtgaccca gcagctgatc agagccgccg agattagagc ctctgccaat 3060

ctggccgcca ccaagatgtc tgagtgtgtg ctgggccaga gcaagagagt ggacttttgc 3120

ggcaagggct accacctgat gagcttccct cagtctgccc ctcacggcgt ggtgtttctg 3180

cacgtgacat atgtgcccgc tcaagagaag aatttcacca ccgctccagc catctgccac 3240

gacggcaaag cccactttcc tagagaaggc gtgttcgtgt ccaacggcac ccattggttc 3300

gtgacacagc ggaacttcta cgagccccag atcatcacca ccgacaacac cttcgtgtct 3360

ggcaactgcg acgtcgtgat cggcattgtg aacaataccg tgtacgaccc tctgcagccc 3420

gagctggaca gcttcaaaga ggaactggac aagtacttta agaaccacac aagccccgac 3480

gtggacctgg gcgatatcag cggaatcaat gccagcgtcg tgaacatcca gaaagagatc 3540

gaccggctga acgaggtggc caagaatctg aacgagagcc tgatcgacct gcaagaactg 3600

gggaagtacg agcagtacat caagtggccc tggtacatct ggctgggctt tatcgccgga 3660

ctgattgcca tcgtgatggt cacaatcatg ctgtgttgca tgaccagctg ctgtagctgc 3720

ctgaagggct gttgtagctg tggcagctgc tgcaagttcg acgaggacga ttctgagccc 3780

gtgctgaagg gcgtgaaact gcactacaca tgatga 3816

<210> 56

<211> 3825

<212> RNA

<213> SARS-CoV-2

<400> 56

auguucgugu uccuggugcu gcugccucug guguccagcc agugugugaa ccugaccacc 60

agaacacagc ugccuccagc cuacaccaac agcuuuacca gaggcgugua cuaccccgac 120

aagguguuca gauccagcgu gcugcacucu acccaggacc uguuccugcc uuucuucagc 180

aacgugaccu gguuccacgc cauccacgug uccggcacca auggcaccaa gagauucgac 240

aaccccgugc ugcccuucaa cgacggggug uacuuugcca gcaccgagaa guccaacauc 300

aucagaggcu ggaucuucgg caccacacug gacagcaaga cccagagccu gcugaucgug 360

aacaacgcca ccaacguggu caucaaagug ugcgaguucc aguucugcaa cgaccccuuc 420

cugggcgucu acuaccacaa gaacaacaag agcuggaugg aaagcgaguu ccggguguac 480

agcagcgcca acaacugcac cuucgaguac gugucccagc cuuuccugau ggaccuggaa 540

ggcaagcagg gcaacuucaa gaaccugcgc gaguucgugu uuaagaacau cgacggcuac 600

uucaagaucu acagcaagca caccccuauc aaccucgugc gggaucugcc ucagggcuuc 660

ucugcucugg aaccccuggu ggaucugccc aucggcauca acaucacccg guuucagaca 720

cugcuggccc ugcacagaag cuaccugaca ccuggcgaua gcagcagcgg auggacagcu 780

ggugccgccg cuuacuaugu gggcuaccug cagccuagaa ccuuccugcu gaaguacaac 840

gagaacggca ccaucaccga cgccguggau ugugcucugg auccucugag cgagacaaag 900

ugcacccuga aguccuucac cguggaaaag ggcaucuacc agaccagcaa cuuccgggug 960

cagcccaccg aauccaucgu gcgguucccc aauaucacca aucugugccc cuucggcgag 1020

guguucaaug ccaccagauu cgccucugug uacgccugga accggaagcg gaucagcaau 1080

ugcguggccg acuacuccgu gcuguacaac uccgccagcu ucagcaccuu caagugcuac 1140

ggcguguccc cuaccaagcu gaacgaccug ugcuucacaa acguguacgc cgacagcuuc 1200

gugauccggg gagaugaagu gcggcagauu gccccuggac agacaggcaa gaucgccgac 1260

uacaacuaca agcugcccga cgacuucacc ggcuguguga uugccuggaa cagcaacaac 1320

cuggacucca aagucggcgg caacuacaau uaccuguacc ggcuguuccg gaaguccaau 1380

cugaagcccu ucgagcggga caucuccacc gagaucuauc aggccggcag caccccuugu 1440

aacggcgugg aaggcuucaa cugcuacuuc ccacugcagu ccuacggcuu ucagcccaca 1500

aauggcgugg gcuaucagcc cuacagagug guggugcuga gcuucgaacu gcugcaugcc 1560

ccugccacag ugugcggccc uaagaaaagc accaaucucg ugaagaacaa augcgugaac 1620

uucaacuuca acggccugac cggcaccggc gugcugacag agagcaacaa gaaguuccug 1680

ccauuccagc aguuuggccg ggauaucgcc gauaccacag acgccguuag agauccccag 1740

acacuggaaa uccuggacau caccccuugc agcuucggcg gagugucugu gaucaccccu 1800

ggcaccaaca ccagcaauca gguggcagug cuguaccagg acgugaacug uaccgaagug 1860

cccguggcca uucacgccga ucagcugaca ccuacauggc ggguguacuc caccggcagc 1920

aauguguuuc agaccagagc cggcugucug aucggagccg agcacgugaa caauagcuac 1980

gagugcgaca uccccaucgg cgcuggaauc ugcgccagcu accagacaca gacaaacagc 2040

ccucggagag ccagaagcgu ggccagccag agcaucauug ccuacacaau gucucugggc 2100

gccgagaaca gcguggccua cuccaacaac ucuaucgcua uccccaccaa cuucaccauc 2160

agcgugacca cagagauccu gccugugucc augaccaaga ccagcgugga cugcaccaug 2220

uacaucugcg gcgauuccac cgagugcucc aaccugcugc ugcaguacgg cagcuucugc 2280

acccagcuga auagagcccu gacagggauc gccguggaac aggacaagaa cacccaagag 2340

guguucgccc aagugaagca gaucuacaag accccuccua ucaaggacuu cggcggcuuc 2400

aauuucagcc agauucugcc cgauccuagc aagcccagca agcggagcuu caucgaggac 2460

cugcuguuca acaaagugac acuggccgac gccggcuuca ucaagcagua uggcgauugu 2520

cugggcgaca uugccgccag ggaucugauu ugcgcccaga aguuuaacgg acugacagug 2580

cugccuccuc ugcugaccga ugagaugauc gcccaguaca caucugcccu gcuggccggc 2640

acaaucacaa gcggcuggac auuuggagca ggcgccgcuc ugcagauccc cuuugcuaug 2700

cagauggccu accgguucaa cggcaucgga gugacccaga augugcugua cgagaaccag 2760

aagcugaucg ccaaccaguu caacagcgcc aucggcaaga uccaggacag ccugagcagc 2820

acagcaagcg cccugggaaa gcugcaggac guggucaacc agaaugccca ggcacugaac 2880

acccugguca agcagcuguc cuccaacuuc ggcgccauca gcucugugcu gaacgauauc 2940

cugagcagac uggacccucc ugaggccgag gugcagaucg acagacugau cacaggcaga 3000

cugcagagcc uccagacaua cgugacccag cagcugauca gagccgccga gauuagagcc 3060

ucugccaauc uggccgccac caagaugucu gagugugugc ugggccagag caagagagug 3120

gacuuuugcg gcaagggcua ccaccugaug agcuucccuc agucugcccc ucacggcgug 3180

guguuucugc acgugacaua ugugcccgcu caagagaaga auuucaccac cgcuccagcc 3240

aucugccacg acggcaaagc ccacuuuccu agagaaggcg uguucguguc caacggcacc 3300

cauugguucg ugacacagcg gaacuucuac gagccccaga ucaucaccac cgacaacacc 3360

uucgugucug gcaacugcga cgucgugauc ggcauuguga acaauaccgu guacgacccu 3420

cugcagcccg agcuggacag cuucaaagag gaacuggaca aguacuuuaa gaaccacaca 3480

agccccgacg uggaccuggg cgauaucagc ggaaucaaug ccagcgucgu gaacauccag 3540

aaagagaucg accggcugaa cgagguggcc aagaaucuga acgagagccu gaucgaccug 3600

caagaacugg ggaaguacga gcaguacauc aaguggcccu gguacaucug gcugggcuuu 3660

aucgccggac ugauugccau cgugaugguc acaaucaugc uguguugcau gaccagcugc 3720

uguagcugcc ugaagggcug uuguagcugu ggcagcugcu gcaaguucga cgaggacgau 3780

ucugagcccg ugcugaaggg cgugaaacug cacuacacau gauga 3825

<210> 57

<211> 3816

<212> RNA

<213> SARS-CoV-2

<400> 57

auguucgugu uccuggugcu gcugccucug guguccagcc agugugugaa ccugaccacc 60

agaacacagc ugccuccagc cuacaccaac agcuuuacca gaggcgugua cuaccccgac 120

aagguguuca gauccagcgu gcugcacucu acccaggacc uguuccugcc uuucuucagc 180

aacgugaccu gguuccacgc caucuccggc accaauggca ccaagagauu cgacaacccc 240

gugcugcccu ucaacgacgg gguguacuuu gccagcaccg agaaguccaa caucaucaga 300

ggcuggaucu ucggcaccac acuggacagc aagacccaga gccugcugau cgugaacaac 360

gccaccaacg uggucaucaa agugugcgag uuccaguucu gcaacgaccc cuuccugggc 420

gucuaccaca agaacaacaa gagcuggaug gaaagcgagu uccgggugua cagcagcgcc 480

aacaacugca ccuucgagua cgugucccag ccuuuccuga uggaccugga aggcaagcag 540

ggcaacuuca agaaccugcg cgaguucgug uuuaagaaca ucgacggcua cuucaagauc 600

uacagcaagc acaccccuau caaccucgug cgggaucugc cucagggcuu cucugcucug 660

gaaccccugg uggaucugcc caucggcauc aacaucaccc gguuucagac acugcuggcc 720

cugcacagaa gcuaccugac accuggcgau agcagcagcg gauggacagc uggugccgcc 780

gcuuacuaug ugggcuaccu gcagccuaga accuuccugc ugaaguacaa cgagaacggc 840

accaucaccg acgccgugga uugugcucug gauccucuga gcgagacaaa gugcacccug 900

aaguccuuca ccguggaaaa gggcaucuac cagaccagca acuuccgggu gcagcccacc 960

gaauccaucg ugcgguuccc caauaucacc aaucugugcc ccuucggcga gguguucaau 1020

gccaccagau ucgccucugu guacgccugg aaccggaagc ggaucagcaa uugcguggcc 1080

gacuacuccg ugcuguacaa cuccgccagc uucagcaccu ucaagugcua cggcgugucc 1140

ccuaccaagc ugaacgaccu gugcuucaca aacguguacg ccgacagcuu cgugauccgg 1200

ggagaugaag ugcggcagau ugccccugga cagacaggca agaucgccga cuacaacuac 1260

aagcugcccg acgacuucac cggcugugug auugccugga acagcaacaa ccuggacucc 1320

aaagucggcg gcaacuacaa uuaccuguac cggcuguucc ggaaguccaa ucugaagccc 1380

uucgagcggg acaucuccac cgagaucuau caggccggca gcaccccuug uaacggcgug 1440

gaaggcuuca acugcuacuu cccacugcag uccuacggcu uucagcccac auacggcgug 1500

ggcuaucagc ccuacagagu gguggugcug agcuucgaac ugcugcaugc cccugccaca 1560

gugugcggcc cuaagaaaag caccaaucuc gugaagaaca aaugcgugaa cuucaacuuc 1620

aacggccuga ccggcaccgg cgugcugaca gagagcaaca agaaguuccu gccauuccag 1680

caguuuggcc gggauaucga cgauaccaca gacgccguua gagaucccca gacacuggaa 1740

auccuggaca ucaccccuug cagcuucggc ggagugucug ugaucacccc uggcaccaac 1800

accagcaauc agguggcagu gcuguaccag ggcgugaacu guaccgaagu gcccguggcc 1860

auucacgccg aucagcugac accuacaugg cggguguacu ccaccggcag caauguguuu 1920

cagaccagag ccggcugucu gaucggagcc gagcacguga acaauagcua cgagugcgac 1980

auccccaucg gcgcuggaau cugcgccagc uaccagacac agacaaacag ccaccggaga 2040

gccagaagcg uggccagcca gagcaucauu gccuacacaa ugucucuggg cgccgagaac 2100

agcguggccu acuccaacaa cucuaucgcu auccccauca acuucaccau cagcgugacc 2160

acagagaucc ugccuguguc caugaccaag accagcgugg acugcaccau guacaucugc 2220

ggcgauucca ccgagugcuc caaccugcug cugcaguacg gcagcuucug cacccagcug 2280

aauagagccc ugacagggau cgccguggaa caggacaaga acacccaaga gguguucgcc 2340

caagugaagc agaucuacaa gaccccuccu aucaaggacu ucggcggcuu caauuucagc 2400

cagauucugc ccgauccuag caagcccagc aagcggagcu ucaucgagga ccugcuguuc 2460

aacaaaguga cacuggccga cgccggcuuc aucaagcagu auggcgauug ucugggcgac 2520

auugccgcca gggaucugau uugcgcccag aaguuuaacg gacugacagu gcugccuccu 2580

cugcugaccg augagaugau cgcccaguac acaucugccc ugcuggccgg cacaaucaca 2640

agcggcugga cauuuggagc aggcgccgcu cugcagaucc ccuuugcuau gcagauggcc 2700

uaccgguuca acggcaucgg agugacccag aaugugcugu acgagaacca gaagcugauc 2760

gccaaccagu ucaacagcgc caucggcaag auccaggaca gccugagcag cacagcaagc 2820

gcccugggaa agcugcagga cguggucaac cagaaugccc aggcacugaa cacccugguc 2880

aagcagcugu ccuccaacuu cggcgccauc agcucugugc ugaacgauau ccuggcaaga 2940

cuggacccuc cugaggccga ggugcagauc gacagacuga ucacaggcag acugcagagc 3000

cuccagacau acgugaccca gcagcugauc agagccgccg agauuagagc cucugccaau 3060

cuggccgcca ccaagauguc ugagugugug cugggccaga gcaagagagu ggacuuuugc 3120

ggcaagggcu accaccugau gagcuucccu cagucugccc cucacggcgu gguguuucug 3180

cacgugacau augugcccgc ucaagagaag aauuucacca ccgcuccagc caucugccac 3240

gacggcaaag cccacuuucc uagagaaggc guguucgugu ccaacggcac ccauugguuc 3300

gugacacagc ggaacuucua cgagccccag aucaucacca cccacaacac cuucgugucu 3360

ggcaacugcg acgucgugau cggcauugug aacaauaccg uguacgaccc ucugcagccc 3420

gagcuggaca gcuucaaaga ggaacuggac aaguacuuua agaaccacac aagccccgac 3480

guggaccugg gcgauaucag cggaaucaau gccagcgucg ugaacaucca gaaagagauc 3540

gaccggcuga acgagguggc caagaaucug aacgagagcc ugaucgaccu gcaagaacug 3600

gggaaguacg agcaguacau caaguggccc ugguacaucu ggcugggcuu uaucgccgga 3660

cugauugcca ucgugauggu cacaaucaug cuguguugca ugaccagcug cuguagcugc 3720

cugaagggcu guuguagcug uggcagcugc ugcaaguucg acgaggacga uucugagccc 3780

gugcugaagg gcgugaaacu gcacuacaca ugauga 3816

<210> 58

<211> 3816

<212> RNA

<213> SARS-CoV-2

<400> 58

auguucgugu uccuggugcu gcugccucug guguccagcc agugugugaa cuucaccacc 60

agaacacagc ugccuccagc cuacaccaac agcuuuacca gaggcgugua cuaccccgac 120

aagguguuca gauccagcgu gcugcacucu acccaggacc uguuccugcc uuucuucagc 180

aacgugaccu gguuccacgc cauccacgug uccggcacca auggcaccaa gagauucgcc 240

aaccccgugc ugcccuucaa cgacggggug uacuuugcca gcaccgagaa guccaacauc 300

aucagaggcu ggaucuucgg caccacacug gacagcaaga cccagagccu gcugaucgug 360

aacaacgcca ccaacguggu caucaaagug ugcgaguucc aguucugcaa cgaccccuuc 420

cugggcgucu acuaccacaa gaacaacaag agcuggaugg aaagcgaguu ccggguguac 480

agcagcgcca acaacugcac cuucgaguac gugucccagc cuuuccugau ggaccuggaa 540

ggcaagcagg gcaacuucaa gaaccugcgc gaguucgugu uuaagaacau cgacggcuac 600

uucaagaucu acagcaagca caccccuauc aaccucgugc ggggucugcc ucagggcuuc 660

ucugcucugg aaccccuggu ggaucugccc aucggcauca acaucacccg guuucagaca 720

cugcacagaa gcuaccugac accuggcgau agcagcagcg gauggacagc uggugccgcc 780

gcuuacuaug ugggcuaccu gcagccuaga accuuccugc ugaaguacaa cgagaacggc 840

accaucaccg acgccgugga uugugcucug gauccucuga gcgagacaaa gugcacccug 900

aaguccuuca ccguggaaaa gggcaucuac cagaccagca acuuccgggu gcagcccacc 960

gaauccaucg ugcgguuccc caauaucacc aaucugugcc ccuucggcga gguguucaau 1020

gccaccagau ucgccucugu guacgccugg aaccggaagc ggaucagcaa uugcguggcc 1080

gacuacuccg ugcuguacaa cuccgccagc uucagcaccu ucaagugcua cggcgugucc 1140

ccuaccaagc ugaacgaccu gugcuucaca aacguguacg ccgacagcuu cgugauccgg 1200

ggagaugaag ugcggcagau ugccccugga cagacaggca auaucgccga cuacaacuac 1260

aagcugcccg acgacuucac cggcugugug auugccugga acagcaacaa ccuggacucc 1320

aaagucggcg gcaacuacaa uuaccuguac cggcuguucc ggaaguccaa ucugaagccc 1380

uucgagcggg acaucuccac cgagaucuau caggccggca gcaccccuug uaacggcgug 1440

aaaggcuuca acugcuacuu cccacugcag uccuacggcu uucagcccac auacggcgug 1500

ggcuaucagc ccuacagagu gguggugcug agcuucgaac ugcugcaugc cccugccaca 1560

gugugcggcc cuaagaaaag caccaaucuc gugaagaaca aaugcgugaa cuucaacuuc 1620

aacggccuga ccggcaccgg cgugcugaca gagagcaaca agaaguuccu gccauuccag 1680

caguuuggcc gggauaucgc cgauaccaca gacgccguua gagaucccca gacacuggaa 1740

auccuggaca ucaccccuug cagcuucggc ggagugucug ugaucacccc uggcaccaac 1800

accagcaauc agguggcagu gcuguaccag ggcgugaacu guaccgaagu gcccguggcc 1860

auucacgccg aucagcugac accuacaugg cggguguacu ccaccggcag caauguguuu 1920

cagaccagag ccggcugucu gaucggagcc gagcacguga acaauagcua cgagugcgac 1980

auccccaucg gcgcuggaau cugcgccagc uaccagacac agacaaacag cccucggaga 2040

gccagaagcg uggccagcca gagcaucauu gccuacacaa ugucucuggg cguggagaac 2100

agcguggccu acuccaacaa cucuaucgcu auccccacca acuucaccau cagcgugacc 2160

acagagaucc ugccuguguc caugaccaag accagcgugg acugcaccau guacaucugc 2220

ggcgauucca ccgagugcuc caaccugcug cugcaguacg gcagcuucug cacccagcug 2280

aauagagccc ugacagggau cgccguggaa caggacaaga acacccaaga gguguucgcc 2340

caagugaagc agaucuacaa gaccccuccu aucaaggacu ucggcggcuu caauuucagc 2400

cagauucugc ccgauccuag caagcccagc aagcggagcu ucaucgagga ccugcuguuc 2460

aacaaaguga cacuggccga cgccggcuuc aucaagcagu auggcgauug ucugggcgac 2520

auugccgcca gggaucugau uugcgcccag aaguuuaacg gacugacagu gcugccuccu 2580

cugcugaccg augagaugau cgcccaguac acaucugccc ugcuggccgg cacaaucaca 2640

agcggcugga cauuuggagc aggcgccgcu cugcagaucc ccuuugcuau gcagauggcc 2700

uaccgguuca acggcaucgg agugacccag aaugugcugu acgagaacca gaagcugauc 2760

gccaaccagu ucaacagcgc caucggcaag auccaggaca gccugagcag cacagcaagc 2820

gcccugggaa agcugcagga cguggucaac cagaaugccc aggcacugaa cacccugguc 2880

aagcagcugu ccuccaacuu cggcgccauc agcucugugc ugaacgauau ccugagcaga 2940

cuggacccuc cugaggccga ggugcagauc gacagacuga ucacaggcag acugcagagc 3000

cuccagacau acgugaccca gcagcugauc agagccgccg agauuagagc cucugccaau 3060

cuggccgcca ccaagauguc ugagugugug cugggccaga gcaagagagu ggacuuuugc 3120

ggcaagggcu accaccugau gagcuucccu cagucugccc cucacggcgu gguguuucug 3180

cacgugacau augugcccgc ucaagagaag aauuucacca ccgcuccagc caucugccac 3240

gacggcaaag cccacuuucc uagagaaggc guguucgugu ccaacggcac ccauugguuc 3300

gugacacagc ggaacuucua cgagccccag aucaucacca ccgacaacac cuucgugucu 3360

ggcaacugcg acgucgugau cggcauugug aacaauaccg uguacgaccc ucugcagccc 3420

gagcuggaca gcuucaaaga ggaacuggac aaguacuuua agaaccacac aagccccgac 3480

guggaccugg gcgauaucag cggaaucaau gccagcgucg ugaacaucca gaaagagauc 3540

gaccggcuga acgagguggc caagaaucug aacgagagcc ugaucgaccu gcaagaacug 3600

gggaaguacg agcaguacau caaguggccc ugguacaucu ggcugggcuu uaucgccgga 3660

cugauugcca ucgugauggu cacaaucaug cuguguugca ugaccagcug cuguagcugc 3720

cugaagggcu guuguagcug uggcagcugc ugcaaguucg acgaggacga uucugagccc 3780

gugcugaagg gcgugaaacu gcacuacaca ugauga 3816

<210> 59

<211> 3825

<212> RNA

<213> SARS-CoV-2

<400> 59

auguucgugu uccuggugcu gcugccccug gugagcuccc agugcgugaa cuuuacaaac 60

agaacacagc ugcccuccgc cuacacaaac agcuucacca ggggcgugua cuaccccgau 120

aaggucuuuc gguccagcgu gcugcacagc acccaggauc uguuccugcc uuucuucagc 180

aacgugacau gguuucacgc cauccacgug agcgggacaa acggcaccaa gcgguucgau 240

aacccagugc ugcccuuuaa cgauggggug uacuucgcca gcacagagaa guccaacauc 300

aucaggggcu ggauuuucgg caccacccuc gauuccaaga cacagucccu gcugaucgug 360

aacaacgcca caaacguggu cauuaaggug ugcgaguucc aguuuugcaa cuacccauuc 420

cugggcgugu acuaccacaa gaacaacaag uccuggaugg agagcgaguu cagggucuac 480

uccuccgcca acaacugcac cuucgaguac gugagccagc ccuuccugau ggaucuggag 540

ggcaagcagg ggaacuucaa gaaccugagc gaguucgugu ucaagaacau ugacggcuac 600

uuuaagaucu acaguaagca cacaccuauc aaccuggugc gggaccugcc ucagggcuuc 660

uccgcccucg agccacuggu ggaucugcca aucggcauua acaucaccag guuccagaca 720

cugcuggccc ugcacaggag cuaccugacu ccaggcgaua gcuccagcgg guggacagcc 780

ggggccgccg ccuacuacgu gggcuaccug cagcccagaa ccuuucugcu gaaguacaac 840

gagaacggga ccaucaccga ugccguggau ugcgcccugg acccccugag cgagaccaag 900

ugcacucuca aguccuucac cguggagaag ggcaucuacc agaccagcaa cuuccggguc 960

cagcccacag aguccaucgu gagguucccc aacaucacca accucugccc cuucggcgag 1020

guguucaacg ccaccagguu ugccagcgug uacgccugga acaggaagag gaucuccaac 1080

ugcguggccg auuacagcgu gcuguacaac uccgccuccu ucagcaccuu caagugcuac 1140

ggcgugagcc cuaccaagcu uaacgaucug ugcuuuacaa acguguacgc cgauagcuuu 1200

gugauccggg gggacgaggu gaggcagauu gcccccggcc agacagggac caucgccgau 1260

uacaacuaca agcugcccga ugacuucacc gggugcguga uugccuggaa cagcaacaac 1320

cucgauagca aggucggggg gaacuacaac uaccuguaca ggcuguuuag aaaguccaac 1380

cucaagccuu ucgagcggga uauuagcacu gagaucuacc aggccgggag cacacccugc 1440

aacgggguga agggcuucaa cugcuacuuu ccccugcaga gcuacggcuu ccagccaaca 1500

uacggcgugg gguaccagcc cuaccgggug guggugcuga gcuucgagcu gcugcacgcc 1560

ccugccaccg ugugcggccc caagaaaagc acuaaccugg ugaagaacaa gugcgucaac 1620

uucaacuuua acggccugac cggcacaggg gugcugaccg aguccaacaa gaaguuccug 1680

cccuuccagc aguucggccg ggacaucgcc gauaccacug acgccgugag ggacccccag 1740

acccuggaga uccuggacau uacacccugu agcuucggcg gggucagcgu gaucacaccc 1800

ggcaccaaca cauccaacca gguggccgug cuguaccagg gcgugaacug caccgaggug 1860

cccgucgcca uccacgccga ccagcugaca cccacaugga ggguguacag cacagggagc 1920

aacguguucc agaccagggc cgggugccug aucggcgccg aguacgugaa caacuccuac 1980

gagugcgaca uccccaucgg ggccggcauu ugcgccuccu accagaccca gaccaacagc 2040

ccccggcggg ccaggagcgu ggccagccag agcaucauug ccuacacaau gucucugggc 2100

gccgagaaca gcguggccua cuccaacaac ucuaucgcua uccccaccaa cuucaccauc 2160

agcgugacca cagagauccu gccugugucc augaccaaga ccagcgugga cugcaccaug 2220

uacaucugcg gcgauuccac cgagugcucc aaccugcugc ugcaguacgg cagcuucugc 2280

acccagcuga auagagcccu gacagggauc gccguggaac aggacaagaa cacccaagag 2340

guguucgccc aagugaagca gaucuacaag accccuccua ucaaggacuu cggcggcuuc 2400

aauuucagcc agauucugcc cgauccuagc aagcccagca agcggagcuu caucgaggac 2460

cugcuguuca acaaagugac acuggccgac gccggcuuca ucaagcagua uggcgauugu 2520

cugggcgaca uugccgccag ggaucugauu ugcgcccaga aguuuaacgg acugacagug 2580

cugccuccuc ugcugaccga ugagaugauc gcccaguaca caucugcccu gcuggccggc 2640

acaaucacaa gcggcuggac auuuggagca ggcgccgcuc ugcagauccc cuuugcuaug 2700

cagauggccu accgguucaa cggcaucgga gugacccaga augugcugua cgagaaccag 2760

aagcugaucg ccaaccaguu caacagcgcc aucggcaaga uccaggacag ccugagcagc 2820

acagcaagcg cccugggaaa gcugcaggac guggucaacc agaaugccca ggcacugaac 2880

acccugguca agcagcuguc cuccaacuuc ggcgccauca gcucugugcu gaacgauauc 2940

cugagcagac uggacccucc ugaggccgag gugcagaucg acagacugau cacaggcaga 3000

cugcagagcc uccagacaua cgugacccag cagcugauca gagccgccga gauuagagcc 3060

ucugccaauc uggccgccau caagaugucu gagugugugc ugggccagag caagagagug 3120

gacuuuugcg gcaagggcua ccaccugaug agcuucccuc agucugcccc ucacggcgug 3180

guguuucugc acgugacaua ugugcccgcu caagagaaga auuucaccac cgcuccagcc 3240

aucugccacg acggcaaagc ccacuuuccu agagaaggcg uguucguguc caacggcacc 3300

cauugguucg ugacacagcg gaacuucuac gagccccaga ucaucaccac cgacaacacc 3360

uucgugucug gcaacugcga cgucgugauc ggcauuguga acaauaccgu guacgacccu 3420

cugcagcccg agcuggacag cuucaaagag gaacuggaca aguacuuuaa gaaccacaca 3480

agccccgacg uggaccuggg cgauaucagc ggaaucaaug ccagcuucgu gaacauccag 3540

aaagagaucg accggcugaa cgagguggcc aagaaucuga acgagagccu gaucgaccug 3600

caagaacugg ggaaguacga gcaguacauc aaguggcccu gguacaucug gcugggcuuu 3660

aucgccggac ugauugccau cgugaugguc acaaucaugc uguguugcau gaccagcugc 3720

uguagcugcc ugaagggcug uuguagcugu ggcagcugcu gcaaguucga cgaggacgau 3780

ucugagcccg ugcugaaggg cgugaaacug cacuacacau gauga 3825

<210> 60

<211> 3819

<212> RNA

<213> SARS-CoV-2

<400> 60

auguucgugu uccuggugcu gcugccucug guguccagcc agugugugaa ccugagaacc 60

agaacacagc ugccuccagc cuacaccaac agcuuuacca gaggcgugua cuaccccgac 120

aagguguuca gauccagcgu gcugcacucu acccaggacc uguuccugcc uuucuucagc 180

aacgugaccu gguuccacgc cauccacgug uccggcacca auggcaccaa gagauucgac 240

aaccccgugc ugcccuucaa cgacggggug uacuuugcca gcaccgagaa guccaacauc 300

aucagaggcu ggaucuucgg caccacacug gacagcaaga cccagagccu gcugaucgug 360

aacaacgcca ccaacguggu caucaaagug ugcgaguucc aguucugcaa cgaccccuuc 420

cuggacgucu acuaccacaa gaacaacaag agcuggaugg aaagcggcgu guacagcagc 480

gccaacaacu gcaccuucga guacgugucc cagccuuucc ugauggaccu ggaaggcaag 540

cagggcaacu ucaagaaccu gcgcgaguuc guguuuaaga acaucgacgg cuacuucaag 600

aucuacagca agcacacccc uaucaaccuc gugcgggauc ugccucaggg cuucucugcu 660

cuggaacccc ugguggaucu gcccaucggc aucaacauca cccgguuuca gacacugcug 720

gcccugcaca gaagcuaccu gacaccuggc gauagcagca gcggauggac agcuggugcc 780

gccgcuuacu augugggcua ccugcagccu agaaccuucc ugcugaagua caacgagaac 840

ggcaccauca ccgacgccgu ggauugugcu cuggauccuc ugagcgagac aaagugcacc 900

cugaaguccu ucaccgugga aaagggcauc uaccagacca gcaacuuccg ggugcagccc 960

accgaaucca ucgugcgguu ccccaauauc accaaucugu gccccuucgg cgagguguuc 1020

aaugccacca gauucgccuc uguguacgcc uggaaccgga agcggaucag caauugcgug 1080

gccgacuacu ccgugcugua caacuccgcc agcuucagca ccuucaagug cuacggcgug 1140

uccccuacca agcugaacga ccugugcuuc acaaacgugu acgccgacag cuucgugauc 1200

cggggagaug aagugcggca gauugccccu ggacagacag gcaagaucgc cgacuacaac 1260

uacaagcugc ccgacgacuu caccggcugu gugauugccu ggaacagcaa caaccuggac 1320

uccaaagucg gcggcaacua caauuaccgg uaccggcugu uccggaaguc caaucugaag 1380

cccuucgagc gggacaucuc caccgagauc uaucaggccg gcagcaagcc uuguaacggc 1440

guggaaggcu ucaacugcua cuucccacug caguccuacg gcuuucagcc cacaaauggc 1500

gugggcuauc agcccuacag agugguggug cugagcuucg aacugcugca ugccccugcc 1560

acagugugcg gcccuaagaa aagcaccaau cucgugaaga acaaaugcgu gaacuucaac 1620

uucaacggcc ugaccggcac cggcgugcug acagagagca acaagaaguu ccugccauuc 1680

cagcaguuug gccgggauau cgccgauacc acagacgccg uuagagaucc ccagacacug 1740

gaaauccugg acaucacccc uugcagcuuc ggcggagugu cugugaucac cccuggcacc 1800

aacaccagca aucagguggc agugcuguac cagggcguga acuguaccga agugcccgug 1860

gccauucacg ccgaucagcu gacaccuaca uggcgggugu acuccaccgg cagcaaugug 1920

uuucagacca gagccggcug ucugaucgga gccgagcacg ugaacaauag cuacgagugc 1980

gacaucccca ucggcgcugg aaucugcgcc agcuaccaga cacagacaaa cagccggcgg 2040

agagccagaa gcguggccag ccagagcauc auugccuaca caaugucucu gggcgccgag 2100

aacagcgugg ccuacuccaa caacucuauc gcuaucccca ccaacuucac caucagcgug 2160

accacagaga uccugccugu guccaugacc aagaccagcg uggacugcac cauguacauc 2220

ugcggcgauu ccaccgagug cuccaaccug cugcugcagu acggcagcuu cugcacccag 2280

cugaauagag cccugacagg gaucgccgug gaacaggaca agaacaccca agagguguuc 2340

gcccaaguga agcagaucua caagaccccu ccuaucaagg acuucggcgg cuucaauuuc 2400

agccagauuc ugcccgaucc uagcaagccc agcaagcgga gcuucaucga ggaccugcug 2460

uucaacaaag ugacacuggc cgacgccggc uucaucaagc aguauggcga uugucugggc 2520

gacauugccg ccagggaucu gauuugcgcc cagaaguuua acggacugac agugcugccu 2580

ccucugcuga ccgaugagau gaucgcccag uacacaucug cccugcuggc cggcacaauc 2640

acaagcggcu ggacauuugg agcaggcgcc gcucugcaga uccccuuugc uaugcagaug 2700

gccuaccggu ucaacggcau cggagugacc cagaaugugc uguacgagaa ccagaagcug 2760

aucgccaacc aguucaacag cgccaucggc aagauccagg acagccugag cagcacagca 2820

agcgcccugg gaaagcugca gaacgugguc aaccagaaug cccaggcacu gaacacccug 2880

gucaagcagc uguccuccaa cuucggcgcc aucagcucug ugcugaacga uauccugagc 2940

agacuggacc cuccugaggc cgaggugcag aucgacagac ugaucacagg cagacugcag 3000

agccuccaga cauacgugac ccagcagcug aucagagccg ccgagauuag agccucugcc 3060

aaucuggccg ccaccaagau gucugagugu gugcugggcc agagcaagag aguggacuuu 3120

ugcggcaagg gcuaccaccu gaugagcuuc ccucagucug ccccucacgg cgugguguuu 3180

cugcacguga cauaugugcc cgcucaagag aagaauuuca ccaccgcucc agccaucugc 3240

cacgacggca aagcccacuu uccuagagaa ggcguguucg uguccaacgg cacccauugg 3300

uucgugacac agcggaacuu cuacgagccc cagaucauca ccaccgacaa caccuucgug 3360

ucuggcaacu gcgacgucgu gaucggcauu gugaacaaua ccguguacga cccucugcag 3420

cccgagcugg acagcuucaa agaggaacug gacaaguacu uuaagaacca cacaagcccc 3480

gacguggacc ugggcgauau cagcggaauc aaugccagcg ucgugaacau ccagaaagag 3540

aucgaccggc ugaacgaggu ggccaagaau cugaacgaga gccugaucga ccugcaagaa 3600

cuggggaagu acgagcagua caucaagugg cccugguaca ucuggcuggg cuuuaucgcc 3660

ggacugauug ccaucgugau ggucacaauc augcuguguu gcaugaccag cugcuguagc 3720

ugccugaagg gcuguuguag cuguggcagc ugcugcaagu ucgacgagga cgauucugag 3780

cccgugcuga agggcgugaa acugcacuac acaugauga 3819

<210> 61

<211> 3825

<212> RNA

<213> SARS-CoV-2

<400> 61

auguucgugu uccuggugcu gcugccucug guguccaucc agugugugaa ccugaccacc 60

agaacacagc ugccuccagc cuacaccaac agcuuuacca gaggcgugua cuaccccgac 120

aagguguuca gauccagcgu gcugcacucu acccaggacc uguuccugcc uuucuucagc 180

aacgugaccu gguuccacgc cauccacgug uccggcacca auggcaccaa gagauucgac 240

aaccccgugc ugcccuucaa cgacggggug uacuuugcca gcaccgagaa guccaacauc 300

aucagaggcu ggaucuucgg caccacacug gacagcaaga cccagagccu gcugaucgug 360

aacaacgcca ccaacguggu caucaaagug ugcgaguucc aguucugcaa cgaccccuuc 420

cugggcgucu acuaccacaa gaacaacaag agcugcaugg aaagcgaguu ccggguguac 480

agcagcgcca acaacugcac cuucgaguac gugucccagc cuuuccugau ggaccuggaa 540

ggcaagcagg gcaacuucaa gaaccugcgc gaguucgugu uuaagaacau cgacggcuac 600

uucaagaucu acagcaagca caccccuauc aaccucgugc gggaucugcc ucagggcuuc 660

ucugcucugg aaccccuggu ggaucugccc aucggcauca acaucacccg guuucagaca 720

cugcuggccc ugcacagaag cuaccugaca ccuggcgaua gcagcagcgg auggacagcu 780

ggugccgccg cuuacuaugu gggcuaccug cagccuagaa ccuuccugcu gaaguacaac 840

gagaacggca ccaucaccga cgccguggau ugugcucugg auccucugag cgagacaaag 900

ugcacccuga aguccuucac cguggaaaag ggcaucuacc agaccagcaa cuuccgggug 960

cagcccaccg aauccaucgu gcgguucccc aauaucacca aucugugccc cuucggcgag 1020

guguucaaug ccaccagauu cgccucugug uacgccugga accggaagcg gaucagcaau 1080

ugcguggccg acuacuccgu gcuguacaac uccgccagcu ucagcaccuu caagugcuac 1140

ggcguguccc cuaccaagcu gaacgaccug ugcuucacaa acguguacgc cgacagcuuc 1200

gugauccggg gagaugaagu gcggcagauu gccccuggac agacaggcaa gaucgccgac 1260

uacaacuaca agcugcccga cgacuucacc ggcuguguga uugccuggaa cagcaacaac 1320

cuggacucca aagucggcgg caacuacaau uaccgcuacc ggcuguuccg gaaguccaau 1380

cugaagcccu ucgagcggga caucuccacc gagaucuauc aggccggcag caccccuugu 1440

aacggcgugg aaggcuucaa cugcuacuuc ccacugcagu ccuacggcuu ucagcccaca 1500

aauggcgugg gcuaucagcc cuacagagug guggugcuga gcuucgaacu gcugcaugcc 1560

ccugccacag ugugcggccc uaagaaaagc accaaucucg ugaagaacaa augcgugaac 1620

uucaacuuca acggccugac cggcaccggc gugcugacag agagcaacaa gaaguuccug 1680

ccauuccagc aguuuggccg ggauaucgcc gauaccacag acgccguuag agauccccag 1740

acacuggaaa uccuggacau caccccuugc agcuucggcg gagugucugu gaucaccccu 1800

ggcaccaaca ccagcaauca gguggcagug cuguaccagg gcgugaacug uaccgaagug 1860

cccguggcca uucacgccga ucagcugaca ccuacauggc ggguguacuc caccggcagc 1920

aauguguuuc agaccagagc cggcugucug aucggagccg agcacgugaa caauagcuac 1980

gagugcgaca uccccaucgg cgcuggaauc ugcgccagcu accagacaca gacaaacagc 2040

ccucggagag ccagaagcgu ggccagccag agcaucauug ccuacacaau gucucugggc 2100

gccgagaaca gcguggccua cuccaacaac ucuaucgcua uccccaccaa cuucaccauc 2160

agcgugacca cagagauccu gccugugucc augaccaaga ccagcgugga cugcaccaug 2220

uacaucugcg gcgauuccac cgagugcucc aaccugcugc ugcaguacgg cagcuucugc 2280

acccagcuga auagagcccu gacagggauc gccguggaac aggacaagaa cacccaagag 2340

guguucgccc aagugaagca gaucuacaag accccuccua ucaaggacuu cggcggcuuc 2400

aauuucagcc agauucugcc cgauccuagc aagcccagca agcggagcuu caucgaggac 2460

cugcuguuca acaaagugac acuggccgac gccggcuuca ucaagcagua uggcgauugu 2520

cugggcgaca uugccgccag ggaucugauu ugcgcccaga aguuuaacgg acugacagug 2580

cugccuccuc ugcugaccga ugagaugauc gcccaguaca caucugcccu gcuggccggc 2640

acaaucacaa gcggcuggac auuuggagca ggcgccgcuc ugcagauccc cuuugcuaug 2700

cagauggccu accgguucaa cggcaucgga gugacccaga augugcugua cgagaaccag 2760

aagcugaucg ccaaccaguu caacagcgcc aucggcaaga uccaggacag ccugagcagc 2820

acagcaagcg cccugggaaa gcugcaggac guggucaacc agaaugccca ggcacugaac 2880

acccugguca agcagcuguc cuccaacuuc ggcgccauca gcucugugcu gaacgauauc 2940

cugagcagac uggacccucc ugaggccgag gugcagaucg acagacugau cacaggcaga 3000

cugcagagcc uccagacaua cgugacccag cagcugauca gagccgccga gauuagagcc 3060

ucugccaauc uggccgccac caagaugucu gagugugugc ugggccagag caagagagug 3120

gacuuuugcg gcaagggcua ccaccugaug agcuucccuc agucugcccc ucacggcgug 3180

guguuucugc acgugacaua ugugcccgcu caagagaaga auuucaccac cgcuccagcc 3240

aucugccacg acggcaaagc ccacuuuccu agagaaggcg uguucguguc caacggcacc 3300

cauugguucg ugacacagcg gaacuucuac gagccccaga ucaucaccac cgacaacacc 3360

uucgugucug gcaacugcga cgucgugauc ggcauuguga acaauaccgu guacgacccu 3420

cugcagcccg agcuggacag cuucaaagag gaacuggaca aguacuuuaa gaaccacaca 3480

agccccgacg uggaccuggg cgauaucagc ggaaucaaug ccagcgucgu gaacauccag 3540

aaagagaucg accggcugaa cgagguggcc aagaaucuga acgagagccu gaucgaccug 3600

caagaacugg ggaaguacga gcaguacauc aaguggcccu gguacaucug gcugggcuuu 3660

aucgccggac ugauugccau cgugaugguc acaaucaugc uguguugcau gaccagcugc 3720

uguagcugcc ugaagggcug uuguagcugu ggcagcugcu gcaaguucga cgaggacgau 3780

ucugagcccg ugcugaaggg cgugaaacug cacuacacau gauga 3825

<210> 62

<211> 3816

<212> RNA

<213> SARS-CoV-2

<400> 62

auguucgugu uccuggugcu gcugccucug guguccagcc agugugugaa ccugaccacc 60

agaacacagc ugccuccagc cuacaccaac agcuuuacca gaggcgugua cuaccccgac 120

aagguguuca gauccagcgu gcugcacucu acccaggacc uguuccugcc uuucuucagc 180

aacgugaccu gguuccacgu gaucuccggc accaauggca ccaagagauu cgacaacccc 240

gugcugcccu ucaacgacgg gguguacuuu gccagcaucg agaaguccaa caucaucaga 300

ggcuggaucu ucggcaccac acuggacagc aagacccaga gccugcugau cgugaacaac 360

gccaccaacg uggucaucaa agugugcgag uuccaguucu gcaacgaccc cuuccuggac 420

cacaagaaca acaagagcug gauggaaagc gaguuccggg uguacagcag cgccaacaac 480

ugcaccuucg aguacguguc ccagccuuuc cugauggacc uggaaggcaa gcagggcaac 540

uucaagaacc ugcgcgaguu cguguuuaag aacaucgacg gcuacuucaa gaucuacagc 600

aagcacaccc cuaucaucgu gcgggaaccu gaagaucugc cucagggcuu cucugcucug 660

gaaccccugg uggaucugcc caucggcauc aacaucaccc gguuucagac acugcuggcc 720

cugcacagaa gcuaccugac accuggcgau agcagcagcg gauggacagc uggugccgcc 780

gcuuacuaug ugggcuaccu gcagccuaga accuuccugc ugaaguacaa cgagaacggc 840

accaucaccg acgccgugga uugugcucug gauccucuga gcgagacaaa gugcacccug 900

aaguccuuca ccguggaaaa gggcaucuac cagaccagca acuuccgggu gcagcccacc 960

gaauccaucg ugcgguuccc caauaucacc aaucugugcc ccuucgacga gguguucaau 1020

gccaccagau ucgccucugu guacgccugg aaccggaagc ggaucagcaa uugcguggcc 1080

gacuacuccg ugcuguacaa ccuggccccc uucuucaccu ucaagugcua cggcgugucc 1140

ccuaccaagc ugaacgaccu gugcuucaca aacguguacg ccgacagcuu cgugauccgg 1200

ggagaugaag ugcggcagau ugccccugga cagacaggca acaucgccga cuacaacuac 1260

aagcugcccg acgacuucac cggcugugug auugccugga acagcaacaa gcuggacucc 1320

aaagucuccg gcaacuacaa uuaccuguac cggcuguucc ggaaguccaa ucugaagccc 1380

uucgagcggg acaucuccac cgagaucuau caggccggca acaagccuug uaacggcgug 1440

gccggcuuca acugcuacuu cccacugcgg uccuacuccu uucggcccac auauggcgug 1500

ggccaucagc ccuacagagu gguggugcug agcuucgaac ugcugcaugc cccugccaca 1560

gugugcggcc cuaagaaaag caccaaucuc gugaagaaca aaugcgugaa cuucaacuuc 1620

aacggccuga agggcaccgg cgugcugaca gagagcaaca agaaguuccu gccauuccag 1680

caguuuggcc gggauaucgc cgauaccaca gacgccguua gagaucccca gacacuggaa 1740

auccuggaca ucaccccuug cagcuucggc ggagugucug ugaucacccc uggcaccaac 1800

accagcaauc agguggcagu gcuguaccag ggcgugaacu guaccgaagu gcccguggcc 1860

auucacgccg aucagcugac accuacaugg cggguguacu ccaccggcag caauguguuu 1920

cagaccagag ccggcugucu gaucggagcc gaguacguga acaauagcua cgagugcgac 1980

auccccaucg gcgcuggaau cugcgccagc uaccagacac agacaaagag ccaucggaga 2040

gccagaagcg uggccagcca gagcaucauu gccuacacaa ugucucuggg cgccgagaac 2100

agcguggccu acuccaacaa cucuaucgcu auccccacca acuucaccau cagcgugacc 2160

acagagaucc ugccuguguc caugaccaag accagcgugg acugcaccau guacaucugc 2220

ggcgauucca ccgagugcuc caaccugcug cugcaguacg gcagcuucug cacccagcug 2280

aagagagccc ugacagggau cgccguggaa caggacaaga acacccaaga gguguucgcc 2340

caagugaagc agaucuacaa gaccccuccu aucaaguacu ucggcggcuu caauuucagc 2400

cagauucugc ccgauccuag caagcccagc aagcggagcu ucaucgagga ccugcuguuc 2460

aacaaaguga cacuggccga cgccggcuuc aucaagcagu auggcgauug ucugggcgac 2520

auugccgcca gggaucugau uugcgcccag aaguuuaagg gacugacagu gcugccuccu 2580

cugcugaccg augagaugau cgcccaguac acaucugccc ugcuggccgg cacaaucaca 2640

agcggcugga cauuuggagc aggcgccgcu cugcagaucc ccuuugcuau gcagauggcc 2700

uaccgguuca acggcaucgg agugacccag aaugugcugu acgagaacca gaagcugauc 2760

gccaaccagu ucaacagcgc caucggcaag auccaggaca gccugagcag cacagcaagc 2820

gcccugggaa agcugcagga cguggucaac cacaaugccc aggcacugaa cacccugguc 2880

aagcagcugu ccuccaaguu cggcgccauc agcucugugc ugaacgauau cuucagcaga 2940

cuggacccuc cugaggccga ggugcagauc gacagacuga ucacaggcag acugcagagc 3000

cuccagacau acgugaccca gcagcugauc agagccgccg agauuagagc cucugccaau 3060

cuggccgcca ccaagauguc ugagugugug cugggccaga gcaagagagu ggacuuuugc 3120

ggcaagggcu accaccugau gagcuucccu cagucugccc cucacggcgu gguguuucug 3180

cacgugacau augugcccgc ucaagagaag aauuucacca ccgcuccagc caucugccac 3240

gacggcaaag cccacuuucc uagagaaggc guguucgugu ccaacggcac ccauugguuc 3300

gugacacagc ggaacuucua cgagccccag aucaucacca ccgacaacac cuucgugucu 3360

ggcaacugcg acgucgugau cggcauugug aacaauaccg uguacgaccc ucugcagccc 3420

gagcuggaca gcuucaaaga ggaacuggac aaguacuuua agaaccacac aagccccgac 3480

guggaccugg gcgauaucag cggaaucaau gccagcgucg ugaacaucca gaaagagauc 3540

gaccggcuga acgagguggc caagaaucug aacgagagcc ugaucgaccu gcaagaacug 3600

gggaaguacg agcaguacau caaguggccc ugguacaucu ggcugggcuu uaucgccgga 3660

cugauugcca ucgugauggu cacaaucaug cuguguugca ugaccagcug cuguagcugc 3720

cugaagggcu guuguagcug uggcagcugc ugcaaguucg acgaggacga uucugagccc 3780

gugcugaagg gcgugaaacu gcacuacaca ugauga 3816

<210> 63

<211> 4157

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的野生型S蛋白mRNA

<400> 63

gaguccuccc cauccucucc cucugucccu cugucccucu gacccugcac ugucccagca 60

ccauguucgu guuccuggug cugcugccuc ugguguccag ccagugugug aaccugacca 120

ccagaacaca gcugccucca gccuacacca acagcuuuac cagaggcgug uacuaccccg 180

acaagguguu cagauccagc gugcugcacu cuacccagga ccuguuccug ccuuucuuca 240

gcaacgugac cugguuccac gccauccacg uguccggcac caauggcacc aagagauucg 300

acaaccccgu gcugcccuuc aacgacgggg uguacuuugc cagcaccgag aaguccaaca 360

ucaucagagg cuggaucuuc ggcaccacac uggacagcaa gacccagagc cugcugaucg 420

ugaacaacgc caccaacgug gucaucaaag ugugcgaguu ccaguucugc aacgaccccu 480

uccugggcgu cuacuaccac aagaacaaca agagcuggau ggaaagcgag uuccgggugu 540

acagcagcgc caacaacugc accuucgagu acguguccca gccuuuccug auggaccugg 600

aaggcaagca gggcaacuuc aagaaccugc gcgaguucgu guuuaagaac aucgacggcu 660

acuucaagau cuacagcaag cacaccccua ucaaccucgu gcgggaucug ccucagggcu 720

ucucugcucu ggaaccccug guggaucugc ccaucggcau caacaucacc cgguuucaga 780

cacugcuggc ccugcacaga agcuaccuga caccuggcga uagcagcagc ggauggacag 840

cuggugccgc cgcuuacuau gugggcuacc ugcagccuag aaccuuccug cugaaguaca 900

acgagaacgg caccaucacc gacgccgugg auugugcucu ggauccucug agcgagacaa 960

agugcacccu gaaguccuuc accguggaaa agggcaucua ccagaccagc aacuuccggg 1020

ugcagcccac cgaauccauc gugcgguucc ccaauaucac caaucugugc cccuucggcg 1080

agguguucaa ugccaccaga uucgccucug uguacgccug gaaccggaag cggaucagca 1140

auugcguggc cgacuacucc gugcuguaca acuccgccag cuucagcacc uucaagugcu 1200

acggcguguc cccuaccaag cugaacgacc ugugcuucac aaacguguac gccgacagcu 1260

ucgugauccg gggagaugaa gugcggcaga uugccccugg acagacaggc aagaucgccg 1320

acuacaacua caagcugccc gacgacuuca ccggcugugu gauugccugg aacagcaaca 1380

accuggacuc caaagucggc ggcaacuaca auuaccugua ccggcuguuc cggaagucca 1440

aucugaagcc cuucgagcgg gacaucucca ccgagaucua ucaggccggc agcaccccuu 1500

guaacggcgu ggaaggcuuc aacugcuacu ucccacugca guccuacggc uuucagccca 1560

caaauggcgu gggcuaucag cccuacagag ugguggugcu gagcuucgaa cugcugcaug 1620

ccccugccac agugugcggc ccuaagaaaa gcaccaaucu cgugaagaac aaaugcguga 1680

acuucaacuu caacggccug accggcaccg gcgugcugac agagagcaac aagaaguucc 1740

ugccauucca gcaguuuggc cgggauaucg ccgauaccac agacgccguu agagaucccc 1800

agacacugga aauccuggac aucaccccuu gcagcuucgg cggagugucu gugaucaccc 1860

cuggcaccaa caccagcaau cagguggcag ugcuguacca ggacgugaac uguaccgaag 1920

ugcccguggc cauucacgcc gaucagcuga caccuacaug gcggguguac uccaccggca 1980

gcaauguguu ucagaccaga gccggcuguc ugaucggagc cgagcacgug aacaauagcu 2040

acgagugcga cauccccauc ggcgcuggaa ucugcgccag cuaccagaca cagacaaaca 2100

gcccucggag agccagaagc guggccagcc agagcaucau ugccuacaca augucucugg 2160

gcgccgagaa cagcguggcc uacuccaaca acucuaucgc uauccccacc aacuucacca 2220

ucagcgugac cacagagauc cugccugugu ccaugaccaa gaccagcgug gacugcacca 2280

uguacaucug cggcgauucc accgagugcu ccaaccugcu gcugcaguac ggcagcuucu 2340

gcacccagcu gaauagagcc cugacaggga ucgccgugga acaggacaag aacacccaag 2400

agguguucgc ccaagugaag cagaucuaca agaccccucc uaucaaggac uucggcggcu 2460

ucaauuucag ccagauucug cccgauccua gcaagcccag caagcggagc uucaucgagg 2520

accugcuguu caacaaagug acacuggccg acgccggcuu caucaagcag uauggcgauu 2580

gucugggcga cauugccgcc agggaucuga uuugcgccca gaaguuuaac ggacugacag 2640

ugcugccucc ucugcugacc gaugagauga ucgcccagua cacaucugcc cugcuggccg 2700

gcacaaucac aagcggcugg acauuuggag caggcgccgc ucugcagauc cccuuugcua 2760

ugcagauggc cuaccgguuc aacggcaucg gagugaccca gaaugugcug uacgagaacc 2820

agaagcugau cgccaaccag uucaacagcg ccaucggcaa gauccaggac agccugagca 2880

gcacagcaag cgcccuggga aagcugcagg acguggucaa ccagaaugcc caggcacuga 2940

acacccuggu caagcagcug uccuccaacu ucggcgccau cagcucugug cugaacgaua 3000

uccugagcag acuggacccu ccugaggccg aggugcagau cgacagacug aucacaggca 3060

gacugcagag ccuccagaca uacgugaccc agcagcugau cagagccgcc gagauuagag 3120

ccucugccaa ucuggccgcc accaagaugu cugagugugu gcugggccag agcaagagag 3180

uggacuuuug cggcaagggc uaccaccuga ugagcuuccc ucagucugcc ccucacggcg 3240

ugguguuucu gcacgugaca uaugugcccg cucaagagaa gaauuucacc accgcuccag 3300

ccaucugcca cgacggcaaa gcccacuuuc cuagagaagg cguguucgug uccaacggca 3360

cccauugguu cgugacacag cggaacuucu acgagcccca gaucaucacc accgacaaca 3420

ccuucguguc uggcaacugc gacgucguga ucggcauugu gaacaauacc guguacgacc 3480

cucugcagcc cgagcuggac agcuucaaag aggaacugga caaguacuuu aagaaccaca 3540

caagccccga cguggaccug ggcgauauca gcggaaucaa ugccagcguc gugaacaucc 3600

agaaagagau cgaccggcug aacgaggugg ccaagaaucu gaacgagagc cugaucgacc 3660

ugcaagaacu ggggaaguac gagcaguaca ucaaguggcc cugguacauc uggcugggcu 3720

uuaucgccgg acugauugcc aucgugaugg ucacaaucau gcuguguugc augaccagcu 3780

gcuguagcug ccugaagggc uguuguagcu guggcagcug cugcaaguuc gacgaggacg 3840

auucugagcc cgugcugaag ggcgugaaac ugcacuacac augaugacuc gaggugugug 3900

gaggacaccc ugaacccccc gcuuucaaac aaguuuucaa auuguuugag gucaggauuu 3960

cucaaacuga uuccuuucuu ugcauaugag uauuugaaaa uaaauauuuu cccagaauau 4020

aaauaaauca ucacaugauu auuuuaacua ugcuagcaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaaaa aaaaaaa 4157

<210> 64

<211> 4148

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的α变体S蛋白mRNA

<400> 64

gaguccuccc cauccucucc cucugucccu cugucccucu gacccugcac ugucccagca 60

ccauguucgu guuccuggug cugcugccuc ugguguccag ccagugugug aaccugacca 120

ccagaacaca gcugccucca gccuacacca acagcuuuac cagaggcgug uacuaccccg 180

acaagguguu cagauccagc gugcugcacu cuacccagga ccuguuccug ccuuucuuca 240

gcaacgugac cugguuccac gccaucuccg gcaccaaugg caccaagaga uucgacaacc 300

ccgugcugcc cuucaacgac gggguguacu uugccagcac cgagaagucc aacaucauca 360

gaggcuggau cuucggcacc acacuggaca gcaagaccca gagccugcug aucgugaaca 420

acgccaccaa cguggucauc aaagugugcg aguuccaguu cugcaacgac cccuuccugg 480

gcgucuacca caagaacaac aagagcugga uggaaagcga guuccgggug uacagcagcg 540

ccaacaacug caccuucgag uacguguccc agccuuuccu gauggaccug gaaggcaagc 600

agggcaacuu caagaaccug cgcgaguucg uguuuaagaa caucgacggc uacuucaaga 660

ucuacagcaa gcacaccccu aucaaccucg ugcgggaucu gccucagggc uucucugcuc 720

uggaaccccu gguggaucug cccaucggca ucaacaucac ccgguuucag acacugcugg 780

cccugcacag aagcuaccug acaccuggcg auagcagcag cggauggaca gcuggugccg 840

ccgcuuacua ugugggcuac cugcagccua gaaccuuccu gcugaaguac aacgagaacg 900

gcaccaucac cgacgccgug gauugugcuc uggauccucu gagcgagaca aagugcaccc 960

ugaaguccuu caccguggaa aagggcaucu accagaccag caacuuccgg gugcagccca 1020

ccgaauccau cgugcgguuc cccaauauca ccaaucugug ccccuucggc gagguguuca 1080

augccaccag auucgccucu guguacgccu ggaaccggaa gcggaucagc aauugcgugg 1140

ccgacuacuc cgugcuguac aacuccgcca gcuucagcac cuucaagugc uacggcgugu 1200

ccccuaccaa gcugaacgac cugugcuuca caaacgugua cgccgacagc uucgugaucc 1260

ggggagauga agugcggcag auugccccug gacagacagg caagaucgcc gacuacaacu 1320

acaagcugcc cgacgacuuc accggcugug ugauugccug gaacagcaac aaccuggacu 1380

ccaaagucgg cggcaacuac aauuaccugu accggcuguu ccggaagucc aaucugaagc 1440

ccuucgagcg ggacaucucc accgagaucu aucaggccgg cagcaccccu uguaacggcg 1500

uggaaggcuu caacugcuac uucccacugc aguccuacgg cuuucagccc acauacggcg 1560

ugggcuauca gcccuacaga gugguggugc ugagcuucga acugcugcau gccccugcca 1620

cagugugcgg cccuaagaaa agcaccaauc ucgugaagaa caaaugcgug aacuucaacu 1680

ucaacggccu gaccggcacc ggcgugcuga cagagagcaa caagaaguuc cugccauucc 1740

agcaguuugg ccgggauauc gacgauacca cagacgccgu uagagauccc cagacacugg 1800

aaauccugga caucaccccu ugcagcuucg gcggaguguc ugugaucacc ccuggcacca 1860

acaccagcaa ucagguggca gugcuguacc agggcgugaa cuguaccgaa gugcccgugg 1920

ccauucacgc cgaucagcug acaccuacau ggcgggugua cuccaccggc agcaaugugu 1980

uucagaccag agccggcugu cugaucggag ccgagcacgu gaacaauagc uacgagugcg 2040

acauccccau cggcgcugga aucugcgcca gcuaccagac acagacaaac agccaccgga 2100

gagccagaag cguggccagc cagagcauca uugccuacac aaugucucug ggcgccgaga 2160

acagcguggc cuacuccaac aacucuaucg cuauccccau caacuucacc aucagcguga 2220

ccacagagau ccugccugug uccaugacca agaccagcgu ggacugcacc auguacaucu 2280

gcggcgauuc caccgagugc uccaaccugc ugcugcagua cggcagcuuc ugcacccagc 2340

ugaauagagc ccugacaggg aucgccgugg aacaggacaa gaacacccaa gagguguucg 2400

cccaagugaa gcagaucuac aagaccccuc cuaucaagga cuucggcggc uucaauuuca 2460

gccagauucu gcccgauccu agcaagccca gcaagcggag cuucaucgag gaccugcugu 2520

ucaacaaagu gacacuggcc gacgccggcu ucaucaagca guauggcgau ugucugggcg 2580

acauugccgc cagggaucug auuugcgccc agaaguuuaa cggacugaca gugcugccuc 2640

cucugcugac cgaugagaug aucgcccagu acacaucugc ccugcuggcc ggcacaauca 2700

caagcggcug gacauuugga gcaggcgccg cucugcagau ccccuuugcu augcagaugg 2760

ccuaccgguu caacggcauc ggagugaccc agaaugugcu guacgagaac cagaagcuga 2820

ucgccaacca guucaacagc gccaucggca agauccagga cagccugagc agcacagcaa 2880

gcgcccuggg aaagcugcag gacgugguca accagaaugc ccaggcacug aacacccugg 2940

ucaagcagcu guccuccaac uucggcgcca ucagcucugu gcugaacgau auccuggcaa 3000

gacuggaccc uccugaggcc gaggugcaga ucgacagacu gaucacaggc agacugcaga 3060

gccuccagac auacgugacc cagcagcuga ucagagccgc cgagauuaga gccucugcca 3120

aucuggccgc caccaagaug ucugagugug ugcugggcca gagcaagaga guggacuuuu 3180

gcggcaaggg cuaccaccug augagcuucc cucagucugc cccucacggc gugguguuuc 3240

ugcacgugac auaugugccc gcucaagaga agaauuucac caccgcucca gccaucugcc 3300

acgacggcaa agcccacuuu ccuagagaag gcguguucgu guccaacggc acccauuggu 3360

ucgugacaca gcggaacuuc uacgagcccc agaucaucac cacccacaac accuucgugu 3420

cuggcaacug cgacgucgug aucggcauug ugaacaauac cguguacgac ccucugcagc 3480

ccgagcugga cagcuucaaa gaggaacugg acaaguacuu uaagaaccac acaagccccg 3540

acguggaccu gggcgauauc agcggaauca augccagcgu cgugaacauc cagaaagaga 3600

ucgaccggcu gaacgaggug gccaagaauc ugaacgagag ccugaucgac cugcaagaac 3660

uggggaagua cgagcaguac aucaaguggc ccugguacau cuggcugggc uuuaucgccg 3720

gacugauugc caucgugaug gucacaauca ugcuguguug caugaccagc ugcuguagcu 3780

gccugaaggg cuguuguagc uguggcagcu gcugcaaguu cgacgaggac gauucugagc 3840

ccgugcugaa gggcgugaaa cugcacuaca caugaugacu cgaggugugu ggaggacacc 3900

cugaaccccc cgcuuucaaa caaguuuuca aauuguuuga ggucaggauu ucucaaacug 3960

auuccuuucu uugcauauga guauuugaaa auaaauauuu ucccagaaua uaaauaaauc 4020

aucacaugau uauuuuaacu augcuagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaa 4148

<210> 65

<211> 4148

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的β变体S蛋白mRNA

<400> 65

gaguccuccc cauccucucc cucugucccu cugucccucu gacccugcac ugucccagca 60

ccauguucgu guuccuggug cugcugccuc ugguguccag ccagugugug aacuucacca 120

ccagaacaca gcugccucca gccuacacca acagcuuuac cagaggcgug uacuaccccg 180

acaagguguu cagauccagc gugcugcacu cuacccagga ccuguuccug ccuuucuuca 240

gcaacgugac cugguuccac gccauccacg uguccggcac caauggcacc aagagauucg 300

ccaaccccgu gcugcccuuc aacgacgggg uguacuuugc cagcaccgag aaguccaaca 360

ucaucagagg cuggaucuuc ggcaccacac uggacagcaa gacccagagc cugcugaucg 420

ugaacaacgc caccaacgug gucaucaaag ugugcgaguu ccaguucugc aacgaccccu 480

uccugggcgu cuacuaccac aagaacaaca agagcuggau ggaaagcgag uuccgggugu 540

acagcagcgc caacaacugc accuucgagu acguguccca gccuuuccug auggaccugg 600

aaggcaagca gggcaacuuc aagaaccugc gcgaguucgu guuuaagaac aucgacggcu 660

acuucaagau cuacagcaag cacaccccua ucaaccucgu gcggggucug ccucagggcu 720

ucucugcucu ggaaccccug guggaucugc ccaucggcau caacaucacc cgguuucaga 780

cacugcacag aagcuaccug acaccuggcg auagcagcag cggauggaca gcuggugccg 840

ccgcuuacua ugugggcuac cugcagccua gaaccuuccu gcugaaguac aacgagaacg 900

gcaccaucac cgacgccgug gauugugcuc uggauccucu gagcgagaca aagugcaccc 960

ugaaguccuu caccguggaa aagggcaucu accagaccag caacuuccgg gugcagccca 1020

ccgaauccau cgugcgguuc cccaauauca ccaaucugug ccccuucggc gagguguuca 1080

augccaccag auucgccucu guguacgccu ggaaccggaa gcggaucagc aauugcgugg 1140

ccgacuacuc cgugcuguac aacuccgcca gcuucagcac cuucaagugc uacggcgugu 1200

ccccuaccaa gcugaacgac cugugcuuca caaacgugua cgccgacagc uucgugaucc 1260

ggggagauga agugcggcag auugccccug gacagacagg caauaucgcc gacuacaacu 1320

acaagcugcc cgacgacuuc accggcugug ugauugccug gaacagcaac aaccuggacu 1380

ccaaagucgg cggcaacuac aauuaccugu accggcuguu ccggaagucc aaucugaagc 1440

ccuucgagcg ggacaucucc accgagaucu aucaggccgg cagcaccccu uguaacggcg 1500

ugaaaggcuu caacugcuac uucccacugc aguccuacgg cuuucagccc acauacggcg 1560

ugggcuauca gcccuacaga gugguggugc ugagcuucga acugcugcau gccccugcca 1620

cagugugcgg cccuaagaaa agcaccaauc ucgugaagaa caaaugcgug aacuucaacu 1680

ucaacggccu gaccggcacc ggcgugcuga cagagagcaa caagaaguuc cugccauucc 1740

agcaguuugg ccgggauauc gccgauacca cagacgccgu uagagauccc cagacacugg 1800

aaauccugga caucaccccu ugcagcuucg gcggaguguc ugugaucacc ccuggcacca 1860

acaccagcaa ucagguggca gugcuguacc agggcgugaa cuguaccgaa gugcccgugg 1920

ccauucacgc cgaucagcug acaccuacau ggcgggugua cuccaccggc agcaaugugu 1980

uucagaccag agccggcugu cugaucggag ccgagcacgu gaacaauagc uacgagugcg 2040

acauccccau cggcgcugga aucugcgcca gcuaccagac acagacaaac agcccucgga 2100

gagccagaag cguggccagc cagagcauca uugccuacac aaugucucug ggcguggaga 2160

acagcguggc cuacuccaac aacucuaucg cuauccccac caacuucacc aucagcguga 2220

ccacagagau ccugccugug uccaugacca agaccagcgu ggacugcacc auguacaucu 2280

gcggcgauuc caccgagugc uccaaccugc ugcugcagua cggcagcuuc ugcacccagc 2340

ugaauagagc ccugacaggg aucgccgugg aacaggacaa gaacacccaa gagguguucg 2400

cccaagugaa gcagaucuac aagaccccuc cuaucaagga cuucggcggc uucaauuuca 2460

gccagauucu gcccgauccu agcaagccca gcaagcggag cuucaucgag gaccugcugu 2520

ucaacaaagu gacacuggcc gacgccggcu ucaucaagca guauggcgau ugucugggcg 2580

acauugccgc cagggaucug auuugcgccc agaaguuuaa cggacugaca gugcugccuc 2640

cucugcugac cgaugagaug aucgcccagu acacaucugc ccugcuggcc ggcacaauca 2700

caagcggcug gacauuugga gcaggcgccg cucugcagau ccccuuugcu augcagaugg 2760

ccuaccgguu caacggcauc ggagugaccc agaaugugcu guacgagaac cagaagcuga 2820

ucgccaacca guucaacagc gccaucggca agauccagga cagccugagc agcacagcaa 2880

gcgcccuggg aaagcugcag gacgugguca accagaaugc ccaggcacug aacacccugg 2940

ucaagcagcu guccuccaac uucggcgcca ucagcucugu gcugaacgau auccugagca 3000

gacuggaccc uccugaggcc gaggugcaga ucgacagacu gaucacaggc agacugcaga 3060

gccuccagac auacgugacc cagcagcuga ucagagccgc cgagauuaga gccucugcca 3120

aucuggccgc caccaagaug ucugagugug ugcugggcca gagcaagaga guggacuuuu 3180

gcggcaaggg cuaccaccug augagcuucc cucagucugc cccucacggc gugguguuuc 3240

ugcacgugac auaugugccc gcucaagaga agaauuucac caccgcucca gccaucugcc 3300

acgacggcaa agcccacuuu ccuagagaag gcguguucgu guccaacggc acccauuggu 3360

ucgugacaca gcggaacuuc uacgagcccc agaucaucac caccgacaac accuucgugu 3420

cuggcaacug cgacgucgug aucggcauug ugaacaauac cguguacgac ccucugcagc 3480

ccgagcugga cagcuucaaa gaggaacugg acaaguacuu uaagaaccac acaagccccg 3540

acguggaccu gggcgauauc agcggaauca augccagcgu cgugaacauc cagaaagaga 3600

ucgaccggcu gaacgaggug gccaagaauc ugaacgagag ccugaucgac cugcaagaac 3660

uggggaagua cgagcaguac aucaaguggc ccugguacau cuggcugggc uuuaucgccg 3720

gacugauugc caucgugaug gucacaauca ugcuguguug caugaccagc ugcuguagcu 3780

gccugaaggg cuguuguagc uguggcagcu gcugcaaguu cgacgaggac gauucugagc 3840

ccgugcugaa gggcgugaaa cugcacuaca caugaugacu cgaggugugu ggaggacacc 3900

cugaaccccc cgcuuucaaa caaguuuuca aauuguuuga ggucaggauu ucucaaacug 3960

auuccuuucu uugcauauga guauuugaaa auaaauauuu ucccagaaua uaaauaaauc 4020

aucacaugau uauuuuaacu augcuagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaa 4148

<210> 66

<211> 4157

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的δ变体S蛋白mRNA

<400> 66

gaguccuccc cauccucucc cucugucccu cugucccucu gacccugcac ugucccagca 60

ccauguucgu guuccuggug cugcugcccc uggugagcuc ccagugcgug aacuuuacaa 120

acagaacaca gcugcccucc gccuacacaa acagcuucac caggggcgug uacuaccccg 180

auaaggucuu ucgguccagc gugcugcaca gcacccagga ucuguuccug ccuuucuuca 240

gcaacgugac augguuucac gccauccacg ugagcgggac aaacggcacc aagcgguucg 300

auaacccagu gcugcccuuu aacgaugggg uguacuucgc cagcacagag aaguccaaca 360

ucaucagggg cuggauuuuc ggcaccaccc ucgauuccaa gacacagucc cugcugaucg 420

ugaacaacgc cacaaacgug gucauuaagg ugugcgaguu ccaguuuugc aacuacccau 480

uccugggcgu guacuaccac aagaacaaca aguccuggau ggagagcgag uucagggucu 540

acuccuccgc caacaacugc accuucgagu acgugagcca gcccuuccug auggaucugg 600

agggcaagca ggggaacuuc aagaaccuga gcgaguucgu guucaagaac auugacggcu 660

acuuuaagau cuacaguaag cacacaccua ucaaccuggu gcgggaccug ccucagggcu 720

ucuccgcccu cgagccacug guggaucugc caaucggcau uaacaucacc agguuccaga 780

cacugcuggc ccugcacagg agcuaccuga cuccaggcga uagcuccagc ggguggacag 840

ccggggccgc cgccuacuac gugggcuacc ugcagcccag aaccuuucug cugaaguaca 900

acgagaacgg gaccaucacc gaugccgugg auugcgcccu ggacccccug agcgagacca 960

agugcacucu caaguccuuc accguggaga agggcaucua ccagaccagc aacuuccggg 1020

uccagcccac agaguccauc gugagguucc ccaacaucac caaccucugc cccuucggcg 1080

agguguucaa cgccaccagg uuugccagcg uguacgccug gaacaggaag aggaucucca 1140

acugcguggc cgauuacagc gugcuguaca acuccgccuc cuucagcacc uucaagugcu 1200

acggcgugag cccuaccaag cuuaacgauc ugugcuuuac aaacguguac gccgauagcu 1260

uugugauccg gggggacgag gugaggcaga uugcccccgg ccagacaggg accaucgccg 1320

auuacaacua caagcugccc gaugacuuca ccgggugcgu gauugccugg aacagcaaca 1380

accucgauag caaggucggg gggaacuaca acuaccugua caggcuguuu agaaagucca 1440

accucaagcc uuucgagcgg gauauuagca cugagaucua ccaggccggg agcacacccu 1500

gcaacggggu gaagggcuuc aacugcuacu uuccccugca gagcuacggc uuccagccaa 1560

cauacggcgu gggguaccag cccuaccggg ugguggugcu gagcuucgag cugcugcacg 1620

ccccugccac cgugugcggc cccaagaaaa gcacuaaccu ggugaagaac aagugcguca 1680

acuucaacuu uaacggccug accggcacag gggugcugac cgaguccaac aagaaguucc 1740

ugcccuucca gcaguucggc cgggacaucg ccgauaccac ugacgccgug agggaccccc 1800

agacccugga gauccuggac auuacacccu guagcuucgg cggggucagc gugaucacac 1860

ccggcaccaa cacauccaac cagguggccg ugcuguacca gggcgugaac ugcaccgagg 1920

ugcccgucgc cauccacgcc gaccagcuga cacccacaug gaggguguac agcacaggga 1980

gcaacguguu ccagaccagg gccgggugcc ugaucggcgc cgaguacgug aacaacuccu 2040

acgagugcga cauccccauc ggggccggca uuugcgccuc cuaccagacc cagaccaaca 2100

gcccccggcg ggccaggagc guggccagcc agagcaucau ugccuacaca augucucugg 2160

gcgccgagaa cagcguggcc uacuccaaca acucuaucgc uauccccacc aacuucacca 2220

ucagcgugac cacagagauc cugccugugu ccaugaccaa gaccagcgug gacugcacca 2280

uguacaucug cggcgauucc accgagugcu ccaaccugcu gcugcaguac ggcagcuucu 2340

gcacccagcu gaauagagcc cugacaggga ucgccgugga acaggacaag aacacccaag 2400

agguguucgc ccaagugaag cagaucuaca agaccccucc uaucaaggac uucggcggcu 2460

ucaauuucag ccagauucug cccgauccua gcaagcccag caagcggagc uucaucgagg 2520

accugcuguu caacaaagug acacuggccg acgccggcuu caucaagcag uauggcgauu 2580

gucugggcga cauugccgcc agggaucuga uuugcgccca gaaguuuaac ggacugacag 2640

ugcugccucc ucugcugacc gaugagauga ucgcccagua cacaucugcc cugcuggccg 2700

gcacaaucac aagcggcugg acauuuggag caggcgccgc ucugcagauc cccuuugcua 2760

ugcagauggc cuaccgguuc aacggcaucg gagugaccca gaaugugcug uacgagaacc 2820

agaagcugau cgccaaccag uucaacagcg ccaucggcaa gauccaggac agccugagca 2880

gcacagcaag cgcccuggga aagcugcagg acguggucaa ccagaaugcc caggcacuga 2940

acacccuggu caagcagcug uccuccaacu ucggcgccau cagcucugug cugaacgaua 3000

uccugagcag acuggacccu ccugaggccg aggugcagau cgacagacug aucacaggca 3060

gacugcagag ccuccagaca uacgugaccc agcagcugau cagagccgcc gagauuagag 3120

ccucugccaa ucuggccgcc aucaagaugu cugagugugu gcugggccag agcaagagag 3180

uggacuuuug cggcaagggc uaccaccuga ugagcuuccc ucagucugcc ccucacggcg 3240

ugguguuucu gcacgugaca uaugugcccg cucaagagaa gaauuucacc accgcuccag 3300

ccaucugcca cgacggcaaa gcccacuuuc cuagagaagg cguguucgug uccaacggca 3360

cccauugguu cgugacacag cggaacuucu acgagcccca gaucaucacc accgacaaca 3420

ccuucguguc uggcaacugc gacgucguga ucggcauugu gaacaauacc guguacgacc 3480

cucugcagcc cgagcuggac agcuucaaag aggaacugga caaguacuuu aagaaccaca 3540

caagccccga cguggaccug ggcgauauca gcggaaucaa ugccagcuuc gugaacaucc 3600

agaaagagau cgaccggcug aacgaggugg ccaagaaucu gaacgagagc cugaucgacc 3660

ugcaagaacu ggggaaguac gagcaguaca ucaaguggcc cugguacauc uggcugggcu 3720

uuaucgccgg acugauugcc aucgugaugg ucacaaucau gcuguguugc augaccagcu 3780

gcuguagcug ccugaagggc uguuguagcu guggcagcug cugcaaguuc gacgaggacg 3840

auucugagcc cgugcugaag ggcgugaaac ugcacuacac augaugacuc gaggugugug 3900

gaggacaccc ugaacccccc gcuuucaaac aaguuuucaa auuguuugag gucaggauuu 3960

cucaaacuga uuccuuucuu ugcauaugag uauuugaaaa uaaauauuuu cccagaauau 4020

aaauaaauca ucacaugauu auuuuaacua ugcuagcaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaaaa aaaaaaa 4157

<210> 67

<211> 4151

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的δ变体蛋白mRNA

<400> 67

gaguccuccc cauccucucc cucugucccu cugucccucu gacccugcac ugucccagca 60

ccauguucgu guuccuggug cugcugccuc ugguguccag ccagugugug aaccugagaa 120

ccagaacaca gcugccucca gccuacacca acagcuuuac cagaggcgug uacuaccccg 180

acaagguguu cagauccagc gugcugcacu cuacccagga ccuguuccug ccuuucuuca 240

gcaacgugac cugguuccac gccauccacg uguccggcac caauggcacc aagagauucg 300

acaaccccgu gcugcccuuc aacgacgggg uguacuuugc cagcaccgag aaguccaaca 360

ucaucagagg cuggaucuuc ggcaccacac uggacagcaa gacccagagc cugcugaucg 420

ugaacaacgc caccaacgug gucaucaaag ugugcgaguu ccaguucugc aacgaccccu 480

uccuggacgu cuacuaccac aagaacaaca agagcuggau ggaaagcggc guguacagca 540

gcgccaacaa cugcaccuuc gaguacgugu cccagccuuu ccugauggac cuggaaggca 600

agcagggcaa cuucaagaac cugcgcgagu ucguguuuaa gaacaucgac ggcuacuuca 660

agaucuacag caagcacacc ccuaucaacc ucgugcggga ucugccucag ggcuucucug 720

cucuggaacc ccugguggau cugcccaucg gcaucaacau cacccgguuu cagacacugc 780

uggcccugca cagaagcuac cugacaccug gcgauagcag cagcggaugg acagcuggug 840

ccgccgcuua cuaugugggc uaccugcagc cuagaaccuu ccugcugaag uacaacgaga 900

acggcaccau caccgacgcc guggauugug cucuggaucc ucugagcgag acaaagugca 960

cccugaaguc cuucaccgug gaaaagggca ucuaccagac cagcaacuuc cgggugcagc 1020

ccaccgaauc caucgugcgg uuccccaaua ucaccaaucu gugccccuuc ggcgaggugu 1080

ucaaugccac cagauucgcc ucuguguacg ccuggaaccg gaagcggauc agcaauugcg 1140

uggccgacua cuccgugcug uacaacuccg ccagcuucag caccuucaag ugcuacggcg 1200

uguccccuac caagcugaac gaccugugcu ucacaaacgu guacgccgac agcuucguga 1260

uccggggaga ugaagugcgg cagauugccc cuggacagac aggcaagauc gccgacuaca 1320

acuacaagcu gcccgacgac uucaccggcu gugugauugc cuggaacagc aacaaccugg 1380

acuccaaagu cggcggcaac uacaauuacc gguaccggcu guuccggaag uccaaucuga 1440

agcccuucga gcgggacauc uccaccgaga ucuaucaggc cggcagcaag ccuuguaacg 1500

gcguggaagg cuucaacugc uacuucccac ugcaguccua cggcuuucag cccacaaaug 1560

gcgugggcua ucagcccuac agaguggugg ugcugagcuu cgaacugcug caugccccug 1620

ccacagugug cggcccuaag aaaagcacca aucucgugaa gaacaaaugc gugaacuuca 1680

acuucaacgg ccugaccggc accggcgugc ugacagagag caacaagaag uuccugccau 1740

uccagcaguu uggccgggau aucgccgaua ccacagacgc cguuagagau ccccagacac 1800

uggaaauccu ggacaucacc ccuugcagcu ucggcggagu gucugugauc accccuggca 1860

ccaacaccag caaucaggug gcagugcugu accagggcgu gaacuguacc gaagugcccg 1920

uggccauuca cgccgaucag cugacaccua cauggcgggu guacuccacc ggcagcaaug 1980

uguuucagac cagagccggc ugucugaucg gagccgagca cgugaacaau agcuacgagu 2040

gcgacauccc caucggcgcu ggaaucugcg ccagcuacca gacacagaca aacagccggc 2100

ggagagccag aagcguggcc agccagagca ucauugccua cacaaugucu cugggcgccg 2160

agaacagcgu ggccuacucc aacaacucua ucgcuauccc caccaacuuc accaucagcg 2220

ugaccacaga gauccugccu guguccauga ccaagaccag cguggacugc accauguaca 2280

ucugcggcga uuccaccgag ugcuccaacc ugcugcugca guacggcagc uucugcaccc 2340

agcugaauag agcccugaca gggaucgccg uggaacagga caagaacacc caagaggugu 2400

ucgcccaagu gaagcagauc uacaagaccc cuccuaucaa ggacuucggc ggcuucaauu 2460

ucagccagau ucugcccgau ccuagcaagc ccagcaagcg gagcuucauc gaggaccugc 2520

uguucaacaa agugacacug gccgacgccg gcuucaucaa gcaguauggc gauugucugg 2580

gcgacauugc cgccagggau cugauuugcg cccagaaguu uaacggacug acagugcugc 2640

cuccucugcu gaccgaugag augaucgccc aguacacauc ugcccugcug gccggcacaa 2700

ucacaagcgg cuggacauuu ggagcaggcg ccgcucugca gauccccuuu gcuaugcaga 2760

uggccuaccg guucaacggc aucggaguga cccagaaugu gcuguacgag aaccagaagc 2820

ugaucgccaa ccaguucaac agcgccaucg gcaagaucca ggacagccug agcagcacag 2880

caagcgcccu gggaaagcug cagaacgugg ucaaccagaa ugcccaggca cugaacaccc 2940

uggucaagca gcuguccucc aacuucggcg ccaucagcuc ugugcugaac gauauccuga 3000

gcagacugga cccuccugag gccgaggugc agaucgacag acugaucaca ggcagacugc 3060

agagccucca gacauacgug acccagcagc ugaucagagc cgccgagauu agagccucug 3120

ccaaucuggc cgccaccaag augucugagu gugugcuggg ccagagcaag agaguggacu 3180

uuugcggcaa gggcuaccac cugaugagcu ucccucaguc ugccccucac ggcguggugu 3240

uucugcacgu gacauaugug cccgcucaag agaagaauuu caccaccgcu ccagccaucu 3300

gccacgacgg caaagcccac uuuccuagag aaggcguguu cguguccaac ggcacccauu 3360

gguucgugac acagcggaac uucuacgagc cccagaucau caccaccgac aacaccuucg 3420

ugucuggcaa cugcgacguc gugaucggca uugugaacaa uaccguguac gacccucugc 3480

agcccgagcu ggacagcuuc aaagaggaac uggacaagua cuuuaagaac cacacaagcc 3540

ccgacgugga ccugggcgau aucagcggaa ucaaugccag cgucgugaac auccagaaag 3600

agaucgaccg gcugaacgag guggccaaga aucugaacga gagccugauc gaccugcaag 3660

aacuggggaa guacgagcag uacaucaagu ggcccuggua caucuggcug ggcuuuaucg 3720

ccggacugau ugccaucgug auggucacaa ucaugcugug uugcaugacc agcugcugua 3780

gcugccugaa gggcuguugu agcuguggca gcugcugcaa guucgacgag gacgauucug 3840

agcccgugcu gaagggcgug aaacugcacu acacaugaug acucgaggug uguggaggac 3900

acccugaacc ccccgcuuuc aaacaaguuu ucaaauuguu ugaggucagg auuucucaaa 3960

cugauuccuu ucuuugcaua ugaguauuug aaaauaaaua uuuucccaga auauaaauaa 4020

aucaucacau gauuauuuua acuaugcuag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaaaa a 4151

<210> 68

<211> 4157

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的ε变体S蛋白mRNA

<400> 68

gaguccuccc cauccucucc cucugucccu cugucccucu gacccugcac ugucccagca 60

ccauguucgu guuccuggug cugcugccuc ugguguccau ccagugugug aaccugacca 120

ccagaacaca gcugccucca gccuacacca acagcuuuac cagaggcgug uacuaccccg 180

acaagguguu cagauccagc gugcugcacu cuacccagga ccuguuccug ccuuucuuca 240

gcaacgugac cugguuccac gccauccacg uguccggcac caauggcacc aagagauucg 300

acaaccccgu gcugcccuuc aacgacgggg uguacuuugc cagcaccgag aaguccaaca 360

ucaucagagg cuggaucuuc ggcaccacac uggacagcaa gacccagagc cugcugaucg 420

ugaacaacgc caccaacgug gucaucaaag ugugcgaguu ccaguucugc aacgaccccu 480

uccugggcgu cuacuaccac aagaacaaca agagcugcau ggaaagcgag uuccgggugu 540

acagcagcgc caacaacugc accuucgagu acguguccca gccuuuccug auggaccugg 600

aaggcaagca gggcaacuuc aagaaccugc gcgaguucgu guuuaagaac aucgacggcu 660

acuucaagau cuacagcaag cacaccccua ucaaccucgu gcgggaucug ccucagggcu 720

ucucugcucu ggaaccccug guggaucugc ccaucggcau caacaucacc cgguuucaga 780

cacugcuggc ccugcacaga agcuaccuga caccuggcga uagcagcagc ggauggacag 840

cuggugccgc cgcuuacuau gugggcuacc ugcagccuag aaccuuccug cugaaguaca 900

acgagaacgg caccaucacc gacgccgugg auugugcucu ggauccucug agcgagacaa 960

agugcacccu gaaguccuuc accguggaaa agggcaucua ccagaccagc aacuuccggg 1020

ugcagcccac cgaauccauc gugcgguucc ccaauaucac caaucugugc cccuucggcg 1080

agguguucaa ugccaccaga uucgccucug uguacgccug gaaccggaag cggaucagca 1140

auugcguggc cgacuacucc gugcuguaca acuccgccag cuucagcacc uucaagugcu 1200

acggcguguc cccuaccaag cugaacgacc ugugcuucac aaacguguac gccgacagcu 1260

ucgugauccg gggagaugaa gugcggcaga uugccccugg acagacaggc aagaucgccg 1320

acuacaacua caagcugccc gacgacuuca ccggcugugu gauugccugg aacagcaaca 1380

accuggacuc caaagucggc ggcaacuaca auuaccgcua ccggcuguuc cggaagucca 1440

aucugaagcc cuucgagcgg gacaucucca ccgagaucua ucaggccggc agcaccccuu 1500

guaacggcgu ggaaggcuuc aacugcuacu ucccacugca guccuacggc uuucagccca 1560

caaauggcgu gggcuaucag cccuacagag ugguggugcu gagcuucgaa cugcugcaug 1620

ccccugccac agugugcggc ccuaagaaaa gcaccaaucu cgugaagaac aaaugcguga 1680

acuucaacuu caacggccug accggcaccg gcgugcugac agagagcaac aagaaguucc 1740

ugccauucca gcaguuuggc cgggauaucg ccgauaccac agacgccguu agagaucccc 1800

agacacugga aauccuggac aucaccccuu gcagcuucgg cggagugucu gugaucaccc 1860

cuggcaccaa caccagcaau cagguggcag ugcuguacca gggcgugaac uguaccgaag 1920

ugcccguggc cauucacgcc gaucagcuga caccuacaug gcggguguac uccaccggca 1980

gcaauguguu ucagaccaga gccggcuguc ugaucggagc cgagcacgug aacaauagcu 2040

acgagugcga cauccccauc ggcgcuggaa ucugcgccag cuaccagaca cagacaaaca 2100

gcccucggag agccagaagc guggccagcc agagcaucau ugccuacaca augucucugg 2160

gcgccgagaa cagcguggcc uacuccaaca acucuaucgc uauccccacc aacuucacca 2220

ucagcgugac cacagagauc cugccugugu ccaugaccaa gaccagcgug gacugcacca 2280

uguacaucug cggcgauucc accgagugcu ccaaccugcu gcugcaguac ggcagcuucu 2340

gcacccagcu gaauagagcc cugacaggga ucgccgugga acaggacaag aacacccaag 2400

agguguucgc ccaagugaag cagaucuaca agaccccucc uaucaaggac uucggcggcu 2460

ucaauuucag ccagauucug cccgauccua gcaagcccag caagcggagc uucaucgagg 2520

accugcuguu caacaaagug acacuggccg acgccggcuu caucaagcag uauggcgauu 2580

gucugggcga cauugccgcc agggaucuga uuugcgccca gaaguuuaac ggacugacag 2640

ugcugccucc ucugcugacc gaugagauga ucgcccagua cacaucugcc cugcuggccg 2700

gcacaaucac aagcggcugg acauuuggag caggcgccgc ucugcagauc cccuuugcua 2760

ugcagauggc cuaccgguuc aacggcaucg gagugaccca gaaugugcug uacgagaacc 2820

agaagcugau cgccaaccag uucaacagcg ccaucggcaa gauccaggac agccugagca 2880

gcacagcaag cgcccuggga aagcugcagg acguggucaa ccagaaugcc caggcacuga 2940

acacccuggu caagcagcug uccuccaacu ucggcgccau cagcucugug cugaacgaua 3000

uccugagcag acuggacccu ccugaggccg aggugcagau cgacagacug aucacaggca 3060

gacugcagag ccuccagaca uacgugaccc agcagcugau cagagccgcc gagauuagag 3120

ccucugccaa ucuggccgcc accaagaugu cugagugugu gcugggccag agcaagagag 3180

uggacuuuug cggcaagggc uaccaccuga ugagcuuccc ucagucugcc ccucacggcg 3240

ugguguuucu gcacgugaca uaugugcccg cucaagagaa gaauuucacc accgcuccag 3300

ccaucugcca cgacggcaaa gcccacuuuc cuagagaagg cguguucgug uccaacggca 3360

cccauugguu cgugacacag cggaacuucu acgagcccca gaucaucacc accgacaaca 3420

ccuucguguc uggcaacugc gacgucguga ucggcauugu gaacaauacc guguacgacc 3480

cucugcagcc cgagcuggac agcuucaaag aggaacugga caaguacuuu aagaaccaca 3540

caagccccga cguggaccug ggcgauauca gcggaaucaa ugccagcguc gugaacaucc 3600

agaaagagau cgaccggcug aacgaggugg ccaagaaucu gaacgagagc cugaucgacc 3660

ugcaagaacu ggggaaguac gagcaguaca ucaaguggcc cugguacauc uggcugggcu 3720

uuaucgccgg acugauugcc aucgugaugg ucacaaucau gcuguguugc augaccagcu 3780

gcuguagcug ccugaagggc uguuguagcu guggcagcug cugcaaguuc gacgaggacg 3840

auucugagcc cgugcugaag ggcgugaaac ugcacuacac augaugacuc gaggugugug 3900

gaggacaccc ugaacccccc gcuuucaaac aaguuuucaa auuguuugag gucaggauuu 3960

cucaaacuga uuccuuucuu ugcauaugag uauuugaaaa uaaauauuuu cccagaauau 4020

aaauaaauca ucacaugauu auuuuaacua ugcuagcaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaaaa aaaaaaa 4157

<210> 69

<211> 4148

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的ο变体S蛋白mRNA

<400> 69

gaguccuccc cauccucucc cucugucccu cugucccucu gacccugcac ugucccagca 60

ccauguucgu guuccuggug cugcugccuc ugguguccag ccagugugug aaccugacca 120

ccagaacaca gcugccucca gccuacacca acagcuuuac cagaggcgug uacuaccccg 180

acaagguguu cagauccagc gugcugcacu cuacccagga ccuguuccug ccuuucuuca 240

gcaacgugac cugguuccac gugaucuccg gcaccaaugg caccaagaga uucgacaacc 300

ccgugcugcc cuucaacgac gggguguacu uugccagcau cgagaagucc aacaucauca 360

gaggcuggau cuucggcacc acacuggaca gcaagaccca gagccugcug aucgugaaca 420

acgccaccaa cguggucauc aaagugugcg aguuccaguu cugcaacgac cccuuccugg 480

accacaagaa caacaagagc uggauggaaa gcgaguuccg gguguacagc agcgccaaca 540

acugcaccuu cgaguacgug ucccagccuu uccugaugga ccuggaaggc aagcagggca 600

acuucaagaa ccugcgcgag uucguguuua agaacaucga cggcuacuuc aagaucuaca 660

gcaagcacac cccuaucauc gugcgggaac cugaagaucu gccucagggc uucucugcuc 720

uggaaccccu gguggaucug cccaucggca ucaacaucac ccgguuucag acacugcugg 780

cccugcacag aagcuaccug acaccuggcg auagcagcag cggauggaca gcuggugccg 840

ccgcuuacua ugugggcuac cugcagccua gaaccuuccu gcugaaguac aacgagaacg 900

gcaccaucac cgacgccgug gauugugcuc uggauccucu gagcgagaca aagugcaccc 960

ugaaguccuu caccguggaa aagggcaucu accagaccag caacuuccgg gugcagccca 1020

ccgaauccau cgugcgguuc cccaauauca ccaaucugug ccccuucgac gagguguuca 1080

augccaccag auucgccucu guguacgccu ggaaccggaa gcggaucagc aauugcgugg 1140

ccgacuacuc cgugcuguac aaccuggccc ccuucuucac cuucaagugc uacggcgugu 1200

ccccuaccaa gcugaacgac cugugcuuca caaacgugua cgccgacagc uucgugaucc 1260

ggggagauga agugcggcag auugccccug gacagacagg caacaucgcc gacuacaacu 1320

acaagcugcc cgacgacuuc accggcugug ugauugccug gaacagcaac aagcuggacu 1380

ccaaagucuc cggcaacuac aauuaccugu accggcuguu ccggaagucc aaucugaagc 1440

ccuucgagcg ggacaucucc accgagaucu aucaggccgg caacaagccu uguaacggcg 1500

uggccggcuu caacugcuac uucccacugc gguccuacuc cuuucggccc acauauggcg 1560

ugggccauca gcccuacaga gugguggugc ugagcuucga acugcugcau gccccugcca 1620

cagugugcgg cccuaagaaa agcaccaauc ucgugaagaa caaaugcgug aacuucaacu 1680

ucaacggccu gaagggcacc ggcgugcuga cagagagcaa caagaaguuc cugccauucc 1740

agcaguuugg ccgggauauc gccgauacca cagacgccgu uagagauccc cagacacugg 1800

aaauccugga caucaccccu ugcagcuucg gcggaguguc ugugaucacc ccuggcacca 1860

acaccagcaa ucagguggca gugcuguacc agggcgugaa cuguaccgaa gugcccgugg 1920

ccauucacgc cgaucagcug acaccuacau ggcgggugua cuccaccggc agcaaugugu 1980

uucagaccag agccggcugu cugaucggag ccgaguacgu gaacaauagc uacgagugcg 2040

acauccccau cggcgcugga aucugcgcca gcuaccagac acagacaaag agccaucgga 2100

gagccagaag cguggccagc cagagcauca uugccuacac aaugucucug ggcgccgaga 2160

acagcguggc cuacuccaac aacucuaucg cuauccccac caacuucacc aucagcguga 2220

ccacagagau ccugccugug uccaugacca agaccagcgu ggacugcacc auguacaucu 2280

gcggcgauuc caccgagugc uccaaccugc ugcugcagua cggcagcuuc ugcacccagc 2340

ugaagagagc ccugacaggg aucgccgugg aacaggacaa gaacacccaa gagguguucg 2400

cccaagugaa gcagaucuac aagaccccuc cuaucaagua cuucggcggc uucaauuuca 2460

gccagauucu gcccgauccu agcaagccca gcaagcggag cuucaucgag gaccugcugu 2520

ucaacaaagu gacacuggcc gacgccggcu ucaucaagca guauggcgau ugucugggcg 2580

acauugccgc cagggaucug auuugcgccc agaaguuuaa gggacugaca gugcugccuc 2640

cucugcugac cgaugagaug aucgcccagu acacaucugc ccugcuggcc ggcacaauca 2700

caagcggcug gacauuugga gcaggcgccg cucugcagau ccccuuugcu augcagaugg 2760

ccuaccgguu caacggcauc ggagugaccc agaaugugcu guacgagaac cagaagcuga 2820

ucgccaacca guucaacagc gccaucggca agauccagga cagccugagc agcacagcaa 2880

gcgcccuggg aaagcugcag gacgugguca accacaaugc ccaggcacug aacacccugg 2940

ucaagcagcu guccuccaag uucggcgcca ucagcucugu gcugaacgau aucuucagca 3000

gacuggaccc uccugaggcc gaggugcaga ucgacagacu gaucacaggc agacugcaga 3060

gccuccagac auacgugacc cagcagcuga ucagagccgc cgagauuaga gccucugcca 3120

aucuggccgc caccaagaug ucugagugug ugcugggcca gagcaagaga guggacuuuu 3180

gcggcaaggg cuaccaccug augagcuucc cucagucugc cccucacggc gugguguuuc 3240

ugcacgugac auaugugccc gcucaagaga agaauuucac caccgcucca gccaucugcc 3300

acgacggcaa agcccacuuu ccuagagaag gcguguucgu guccaacggc acccauuggu 3360

ucgugacaca gcggaacuuc uacgagcccc agaucaucac caccgacaac accuucgugu 3420

cuggcaacug cgacgucgug aucggcauug ugaacaauac cguguacgac ccucugcagc 3480

ccgagcugga cagcuucaaa gaggaacugg acaaguacuu uaagaaccac acaagccccg 3540

acguggaccu gggcgauauc agcggaauca augccagcgu cgugaacauc cagaaagaga 3600

ucgaccggcu gaacgaggug gccaagaauc ugaacgagag ccugaucgac cugcaagaac 3660

uggggaagua cgagcaguac aucaaguggc ccugguacau cuggcugggc uuuaucgccg 3720

gacugauugc caucgugaug gucacaauca ugcuguguug caugaccagc ugcuguagcu 3780

gccugaaggg cuguuguagc uguggcagcu gcugcaaguu cgacgaggac gauucugagc 3840

ccgugcugaa gggcgugaaa cugcacuaca caugaugacu cgaggugugu ggaggacacc 3900

cugaaccccc cgcuuucaaa caaguuuuca aauuguuuga ggucaggauu ucucaaacug 3960

auuccuuucu uugcauauga guauuugaaa auaaauauuu ucccagaaua uaaauaaauc 4020

aucacaugau uauuuuaacu augcuagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaa 4148

<210> 70

<211> 4157

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的SARS-CoV2 S蛋白mRNA

<400> 70

gagugcuccc cauccaacua aacugucccu cuguccgaac uaaacugcac ugucccagca 60

ccauguucgu guuccuggug cugcugccuc ugguguccag ccagugugug aaccugacca 120

ccagaacaca gcugccucca gccuacacca acagcuuuac cagaggcgug uacuaccccg 180

acaagguguu cagauccagc gugcugcacu cuacccagga ccuguuccug ccuuucuuca 240

gcaacgugac cugguuccac gccauccacg uguccggcac caauggcacc aagagauucg 300

acaaccccgu gcugcccuuc aacgacgggg uguacuuugc cagcaccgag aaguccaaca 360

ucaucagagg cuggaucuuc ggcaccacac uggacagcaa gacccagagc cugcugaucg 420

ugaacaacgc caccaacgug gucaucaaag ugugcgaguu ccaguucugc aacgaccccu 480

uccugggcgu cuacuaccac aagaacaaca agagcuggau ggaaagcgag uuccgggugu 540

acagcagcgc caacaacugc accuucgagu acguguccca gccuuuccug auggaccugg 600

aaggcaagca gggcaacuuc aagaaccugc gcgaguucgu guuuaagaac aucgacggcu 660

acuucaagau cuacagcaag cacaccccua ucaaccucgu gcgggaucug ccucagggcu 720

ucucugcucu ggaaccccug guggaucugc ccaucggcau caacaucacc cgguuucaga 780

cacugcuggc ccugcacaga agcuaccuga caccuggcga uagcagcagc ggauggacag 840

cuggugccgc cgcuuacuau gugggcuacc ugcagccuag aaccuuccug cugaaguaca 900

acgagaacgg caccaucacc gacgccgugg auugugcucu ggauccucug agcgagacaa 960

agugcacccu gaaguccuuc accguggaaa agggcaucua ccagaccagc aacuuccggg 1020

ugcagcccac cgaauccauc gugcgguucc ccaauaucac caaucugugc cccuucggcg 1080

agguguucaa ugccaccaga uucgccucug uguacgccug gaaccggaag cggaucagca 1140

auugcguggc cgacuacucc gugcuguaca acuccgccag cuucagcacc uucaagugcu 1200

acggcguguc cccuaccaag cugaacgacc ugugcuucac aaacguguac gccgacagcu 1260

ucgugauccg gggagaugaa gugcggcaga uugccccugg acagacaggc aagaucgccg 1320

acuacaacua caagcugccc gacgacuuca ccggcugugu gauugccugg aacagcaaca 1380

accuggacuc caaagucggc ggcaacuaca auuaccugua ccggcuguuc cggaagucca 1440

aucugaagcc cuucgagcgg gacaucucca ccgagaucua ucaggccggc agcaccccuu 1500

guaacggcgu ggaaggcuuc aacugcuacu ucccacugca guccuacggc uuucagccca 1560

caaauggcgu gggcuaucag cccuacagag ugguggugcu gagcuucgaa cugcugcaug 1620

ccccugccac agugugcggc ccuaagaaaa gcaccaaucu cgugaagaac aaaugcguga 1680

acuucaacuu caacggccug accggcaccg gcgugcugac agagagcaac aagaaguucc 1740

ugccauucca gcaguuuggc cgggauaucg ccgauaccac agacgccguu agagaucccc 1800

agacacugga aauccuggac aucaccccuu gcagcuucgg cggagugucu gugaucaccc 1860

cuggcaccaa caccagcaau cagguggcag ugcuguacca ggacgugaac uguaccgaag 1920

ugcccguggc cauucacgcc gaucagcuga caccuacaug gcggguguac uccaccggca 1980

gcaauguguu ucagaccaga gccggcuguc ugaucggagc cgagcacgug aacaauagcu 2040

acgagugcga cauccccauc ggcgcuggaa ucugcgccag cuaccagaca cagacaaaca 2100

gcccucggag agccagaagc guggccagcc agagcaucau ugccuacaca augucucugg 2160

gcgccgagaa cagcguggcc uacuccaaca acucuaucgc uauccccacc aacuucacca 2220

ucagcgugac cacagagauc cugccugugu ccaugaccaa gaccagcgug gacugcacca 2280

uguacaucug cggcgauucc accgagugcu ccaaccugcu gcugcaguac ggcagcuucu 2340

gcacccagcu gaauagagcc cugacaggga ucgccgugga acaggacaag aacacccaag 2400

agguguucgc ccaagugaag cagaucuaca agaccccucc uaucaaggac uucggcggcu 2460

ucaauuucag ccagauucug cccgauccua gcaagcccag caagcggagc uucaucgagg 2520

accugcuguu caacaaagug acacuggccg acgccggcuu caucaagcag uauggcgauu 2580

gucugggcga cauugccgcc agggaucuga uuugcgccca gaaguuuaac ggacugacag 2640

ugcugccucc ucugcugacc gaugagauga ucgcccagua cacaucugcc cugcuggccg 2700

gcacaaucac aagcggcugg acauuuggag caggcgccgc ucugcagauc cccuuugcua 2760

ugcagauggc cuaccgguuc aacggcaucg gagugaccca gaaugugcug uacgagaacc 2820

agaagcugau cgccaaccag uucaacagcg ccaucggcaa gauccaggac agccugagca 2880

gcacagcaag cgcccuggga aagcugcagg acguggucaa ccagaaugcc caggcacuga 2940

acacccuggu caagcagcug uccuccaacu ucggcgccau cagcucugug cugaacgaua 3000

uccugagcag acuggacccu ccugaggccg aggugcagau cgacagacug aucacaggca 3060

gacugcagag ccuccagaca uacgugaccc agcagcugau cagagccgcc gagauuagag 3120

ccucugccaa ucuggccgcc accaagaugu cugagugugu gcugggccag agcaagagag 3180

uggacuuuug cggcaagggc uaccaccuga ugagcuuccc ucagucugcc ccucacggcg 3240

ugguguuucu gcacgugaca uaugugcccg cucaagagaa gaauuucacc accgcuccag 3300

ccaucugcca cgacggcaaa gcccacuuuc cuagagaagg cguguucgug uccaacggca 3360

cccauugguu cgugacacag cggaacuucu acgagcccca gaucaucacc accgacaaca 3420

ccuucguguc uggcaacugc gacgucguga ucggcauugu gaacaauacc guguacgacc 3480

cucugcagcc cgagcuggac agcuucaaag aggaacugga caaguacuuu aagaaccaca 3540

caagccccga cguggaccug ggcgauauca gcggaaucaa ugccagcguc gugaacaucc 3600

agaaagagau cgaccggcug aacgaggugg ccaagaaucu gaacgagagc cugaucgacc 3660

ugcaagaacu ggggaaguac gagcaguaca ucaaguggcc cugguacauc uggcugggcu 3720

uuaucgccgg acugauugcc aucgugaugg ucacaaucau gcuguguugc augaccagcu 3780

gcuguagcug ccugaagggc uguuguagcu guggcagcug cugcaaguuc gacgaggacg 3840

auucugagcc cgugcugaag ggcgugaaac ugcacuacac augaugacuc gaggugugug 3900

gaggacaccc ugaacccccc gcuuucaaac aaguuuucaa auuguuugag gucaggauuu 3960

cucaaacuga uuccuuucuu ugcauaugag uauuugaaaa uaaauauuuu cccagaauau 4020

aaauaaauca ucacaugauu auuuuaacua ugcuagcaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaaaa aaaaaaa 4157

<210> 71

<211> 4148

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的α变体S蛋白mRNA

<400> 71

gagugcuccc cauccaacua aacugucccu cuguccgaac uaaacugcac ugucccagca 60

ccauguucgu guuccuggug cugcugccuc ugguguccag ccagugugug aaccugacca 120

ccagaacaca gcugccucca gccuacacca acagcuuuac cagaggcgug uacuaccccg 180

acaagguguu cagauccagc gugcugcacu cuacccagga ccuguuccug ccuuucuuca 240

gcaacgugac cugguuccac gccaucuccg gcaccaaugg caccaagaga uucgacaacc 300

ccgugcugcc cuucaacgac gggguguacu uugccagcac cgagaagucc aacaucauca 360

gaggcuggau cuucggcacc acacuggaca gcaagaccca gagccugcug aucgugaaca 420

acgccaccaa cguggucauc aaagugugcg aguuccaguu cugcaacgac cccuuccugg 480

gcgucuacca caagaacaac aagagcugga uggaaagcga guuccgggug uacagcagcg 540

ccaacaacug caccuucgag uacguguccc agccuuuccu gauggaccug gaaggcaagc 600

agggcaacuu caagaaccug cgcgaguucg uguuuaagaa caucgacggc uacuucaaga 660

ucuacagcaa gcacaccccu aucaaccucg ugcgggaucu gccucagggc uucucugcuc 720

uggaaccccu gguggaucug cccaucggca ucaacaucac ccgguuucag acacugcugg 780

cccugcacag aagcuaccug acaccuggcg auagcagcag cggauggaca gcuggugccg 840

ccgcuuacua ugugggcuac cugcagccua gaaccuuccu gcugaaguac aacgagaacg 900

gcaccaucac cgacgccgug gauugugcuc uggauccucu gagcgagaca aagugcaccc 960

ugaaguccuu caccguggaa aagggcaucu accagaccag caacuuccgg gugcagccca 1020

ccgaauccau cgugcgguuc cccaauauca ccaaucugug ccccuucggc gagguguuca 1080

augccaccag auucgccucu guguacgccu ggaaccggaa gcggaucagc aauugcgugg 1140

ccgacuacuc cgugcuguac aacuccgcca gcuucagcac cuucaagugc uacggcgugu 1200

ccccuaccaa gcugaacgac cugugcuuca caaacgugua cgccgacagc uucgugaucc 1260

ggggagauga agugcggcag auugccccug gacagacagg caagaucgcc gacuacaacu 1320

acaagcugcc cgacgacuuc accggcugug ugauugccug gaacagcaac aaccuggacu 1380

ccaaagucgg cggcaacuac aauuaccugu accggcuguu ccggaagucc aaucugaagc 1440

ccuucgagcg ggacaucucc accgagaucu aucaggccgg cagcaccccu uguaacggcg 1500

uggaaggcuu caacugcuac uucccacugc aguccuacgg cuuucagccc acauacggcg 1560

ugggcuauca gcccuacaga gugguggugc ugagcuucga acugcugcau gccccugcca 1620

cagugugcgg cccuaagaaa agcaccaauc ucgugaagaa caaaugcgug aacuucaacu 1680

ucaacggccu gaccggcacc ggcgugcuga cagagagcaa caagaaguuc cugccauucc 1740

agcaguuugg ccgggauauc gacgauacca cagacgccgu uagagauccc cagacacugg 1800

aaauccugga caucaccccu ugcagcuucg gcggaguguc ugugaucacc ccuggcacca 1860

acaccagcaa ucagguggca gugcuguacc agggcgugaa cuguaccgaa gugcccgugg 1920

ccauucacgc cgaucagcug acaccuacau ggcgggugua cuccaccggc agcaaugugu 1980

uucagaccag agccggcugu cugaucggag ccgagcacgu gaacaauagc uacgagugcg 2040

acauccccau cggcgcugga aucugcgcca gcuaccagac acagacaaac agccaccgga 2100

gagccagaag cguggccagc cagagcauca uugccuacac aaugucucug ggcgccgaga 2160

acagcguggc cuacuccaac aacucuaucg cuauccccau caacuucacc aucagcguga 2220

ccacagagau ccugccugug uccaugacca agaccagcgu ggacugcacc auguacaucu 2280

gcggcgauuc caccgagugc uccaaccugc ugcugcagua cggcagcuuc ugcacccagc 2340

ugaauagagc ccugacaggg aucgccgugg aacaggacaa gaacacccaa gagguguucg 2400

cccaagugaa gcagaucuac aagaccccuc cuaucaagga cuucggcggc uucaauuuca 2460

gccagauucu gcccgauccu agcaagccca gcaagcggag cuucaucgag gaccugcugu 2520

ucaacaaagu gacacuggcc gacgccggcu ucaucaagca guauggcgau ugucugggcg 2580

acauugccgc cagggaucug auuugcgccc agaaguuuaa cggacugaca gugcugccuc 2640

cucugcugac cgaugagaug aucgcccagu acacaucugc ccugcuggcc ggcacaauca 2700

caagcggcug gacauuugga gcaggcgccg cucugcagau ccccuuugcu augcagaugg 2760

ccuaccgguu caacggcauc ggagugaccc agaaugugcu guacgagaac cagaagcuga 2820

ucgccaacca guucaacagc gccaucggca agauccagga cagccugagc agcacagcaa 2880

gcgcccuggg aaagcugcag gacgugguca accagaaugc ccaggcacug aacacccugg 2940

ucaagcagcu guccuccaac uucggcgcca ucagcucugu gcugaacgau auccuggcaa 3000

gacuggaccc uccugaggcc gaggugcaga ucgacagacu gaucacaggc agacugcaga 3060

gccuccagac auacgugacc cagcagcuga ucagagccgc cgagauuaga gccucugcca 3120

aucuggccgc caccaagaug ucugagugug ugcugggcca gagcaagaga guggacuuuu 3180

gcggcaaggg cuaccaccug augagcuucc cucagucugc cccucacggc gugguguuuc 3240

ugcacgugac auaugugccc gcucaagaga agaauuucac caccgcucca gccaucugcc 3300

acgacggcaa agcccacuuu ccuagagaag gcguguucgu guccaacggc acccauuggu 3360

ucgugacaca gcggaacuuc uacgagcccc agaucaucac cacccacaac accuucgugu 3420

cuggcaacug cgacgucgug aucggcauug ugaacaauac cguguacgac ccucugcagc 3480

ccgagcugga cagcuucaaa gaggaacugg acaaguacuu uaagaaccac acaagccccg 3540

acguggaccu gggcgauauc agcggaauca augccagcgu cgugaacauc cagaaagaga 3600

ucgaccggcu gaacgaggug gccaagaauc ugaacgagag ccugaucgac cugcaagaac 3660

uggggaagua cgagcaguac aucaaguggc ccugguacau cuggcugggc uuuaucgccg 3720

gacugauugc caucgugaug gucacaauca ugcuguguug caugaccagc ugcuguagcu 3780

gccugaaggg cuguuguagc uguggcagcu gcugcaaguu cgacgaggac gauucugagc 3840

ccgugcugaa gggcgugaaa cugcacuaca caugaugacu cgaggugugu ggaggacacc 3900

cugaaccccc cgcuuucaaa caaguuuuca aauuguuuga ggucaggauu ucucaaacug 3960

auuccuuucu uugcauauga guauuugaaa auaaauauuu ucccagaaua uaaauaaauc 4020

aucacaugau uauuuuaacu augcuagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaa 4148

<210> 72

<211> 4148

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的β变体S蛋白mRNA

<400> 72

gagugcuccc cauccaacua aacugucccu cuguccgaac uaaacugcac ugucccagca 60

ccauguucgu guuccuggug cugcugccuc ugguguccag ccagugugug aacuucacca 120

ccagaacaca gcugccucca gccuacacca acagcuuuac cagaggcgug uacuaccccg 180

acaagguguu cagauccagc gugcugcacu cuacccagga ccuguuccug ccuuucuuca 240

gcaacgugac cugguuccac gccauccacg uguccggcac caauggcacc aagagauucg 300

ccaaccccgu gcugcccuuc aacgacgggg uguacuuugc cagcaccgag aaguccaaca 360

ucaucagagg cuggaucuuc ggcaccacac uggacagcaa gacccagagc cugcugaucg 420

ugaacaacgc caccaacgug gucaucaaag ugugcgaguu ccaguucugc aacgaccccu 480

uccugggcgu cuacuaccac aagaacaaca agagcuggau ggaaagcgag uuccgggugu 540

acagcagcgc caacaacugc accuucgagu acguguccca gccuuuccug auggaccugg 600

aaggcaagca gggcaacuuc aagaaccugc gcgaguucgu guuuaagaac aucgacggcu 660

acuucaagau cuacagcaag cacaccccua ucaaccucgu gcggggucug ccucagggcu 720

ucucugcucu ggaaccccug guggaucugc ccaucggcau caacaucacc cgguuucaga 780

cacugcacag aagcuaccug acaccuggcg auagcagcag cggauggaca gcuggugccg 840

ccgcuuacua ugugggcuac cugcagccua gaaccuuccu gcugaaguac aacgagaacg 900

gcaccaucac cgacgccgug gauugugcuc uggauccucu gagcgagaca aagugcaccc 960

ugaaguccuu caccguggaa aagggcaucu accagaccag caacuuccgg gugcagccca 1020

ccgaauccau cgugcgguuc cccaauauca ccaaucugug ccccuucggc gagguguuca 1080

augccaccag auucgccucu guguacgccu ggaaccggaa gcggaucagc aauugcgugg 1140

ccgacuacuc cgugcuguac aacuccgcca gcuucagcac cuucaagugc uacggcgugu 1200

ccccuaccaa gcugaacgac cugugcuuca caaacgugua cgccgacagc uucgugaucc 1260

ggggagauga agugcggcag auugccccug gacagacagg caauaucgcc gacuacaacu 1320

acaagcugcc cgacgacuuc accggcugug ugauugccug gaacagcaac aaccuggacu 1380

ccaaagucgg cggcaacuac aauuaccugu accggcuguu ccggaagucc aaucugaagc 1440

ccuucgagcg ggacaucucc accgagaucu aucaggccgg cagcaccccu uguaacggcg 1500

ugaaaggcuu caacugcuac uucccacugc aguccuacgg cuuucagccc acauacggcg 1560

ugggcuauca gcccuacaga gugguggugc ugagcuucga acugcugcau gccccugcca 1620

cagugugcgg cccuaagaaa agcaccaauc ucgugaagaa caaaugcgug aacuucaacu 1680

ucaacggccu gaccggcacc ggcgugcuga cagagagcaa caagaaguuc cugccauucc 1740

agcaguuugg ccgggauauc gccgauacca cagacgccgu uagagauccc cagacacugg 1800

aaauccugga caucaccccu ugcagcuucg gcggaguguc ugugaucacc ccuggcacca 1860

acaccagcaa ucagguggca gugcuguacc agggcgugaa cuguaccgaa gugcccgugg 1920

ccauucacgc cgaucagcug acaccuacau ggcgggugua cuccaccggc agcaaugugu 1980

uucagaccag agccggcugu cugaucggag ccgagcacgu gaacaauagc uacgagugcg 2040

acauccccau cggcgcugga aucugcgcca gcuaccagac acagacaaac agcccucgga 2100

gagccagaag cguggccagc cagagcauca uugccuacac aaugucucug ggcguggaga 2160

acagcguggc cuacuccaac aacucuaucg cuauccccac caacuucacc aucagcguga 2220

ccacagagau ccugccugug uccaugacca agaccagcgu ggacugcacc auguacaucu 2280

gcggcgauuc caccgagugc uccaaccugc ugcugcagua cggcagcuuc ugcacccagc 2340

ugaauagagc ccugacaggg aucgccgugg aacaggacaa gaacacccaa gagguguucg 2400

cccaagugaa gcagaucuac aagaccccuc cuaucaagga cuucggcggc uucaauuuca 2460

gccagauucu gcccgauccu agcaagccca gcaagcggag cuucaucgag gaccugcugu 2520

ucaacaaagu gacacuggcc gacgccggcu ucaucaagca guauggcgau ugucugggcg 2580

acauugccgc cagggaucug auuugcgccc agaaguuuaa cggacugaca gugcugccuc 2640

cucugcugac cgaugagaug aucgcccagu acacaucugc ccugcuggcc ggcacaauca 2700

caagcggcug gacauuugga gcaggcgccg cucugcagau ccccuuugcu augcagaugg 2760

ccuaccgguu caacggcauc ggagugaccc agaaugugcu guacgagaac cagaagcuga 2820

ucgccaacca guucaacagc gccaucggca agauccagga cagccugagc agcacagcaa 2880

gcgcccuggg aaagcugcag gacgugguca accagaaugc ccaggcacug aacacccugg 2940

ucaagcagcu guccuccaac uucggcgcca ucagcucugu gcugaacgau auccugagca 3000

gacuggaccc uccugaggcc gaggugcaga ucgacagacu gaucacaggc agacugcaga 3060

gccuccagac auacgugacc cagcagcuga ucagagccgc cgagauuaga gccucugcca 3120

aucuggccgc caccaagaug ucugagugug ugcugggcca gagcaagaga guggacuuuu 3180

gcggcaaggg cuaccaccug augagcuucc cucagucugc cccucacggc gugguguuuc 3240

ugcacgugac auaugugccc gcucaagaga agaauuucac caccgcucca gccaucugcc 3300

acgacggcaa agcccacuuu ccuagagaag gcguguucgu guccaacggc acccauuggu 3360

ucgugacaca gcggaacuuc uacgagcccc agaucaucac caccgacaac accuucgugu 3420

cuggcaacug cgacgucgug aucggcauug ugaacaauac cguguacgac ccucugcagc 3480

ccgagcugga cagcuucaaa gaggaacugg acaaguacuu uaagaaccac acaagccccg 3540

acguggaccu gggcgauauc agcggaauca augccagcgu cgugaacauc cagaaagaga 3600

ucgaccggcu gaacgaggug gccaagaauc ugaacgagag ccugaucgac cugcaagaac 3660

uggggaagua cgagcaguac aucaaguggc ccugguacau cuggcugggc uuuaucgccg 3720

gacugauugc caucgugaug gucacaauca ugcuguguug caugaccagc ugcuguagcu 3780

gccugaaggg cuguuguagc uguggcagcu gcugcaaguu cgacgaggac gauucugagc 3840

ccgugcugaa gggcgugaaa cugcacuaca caugaugacu cgaggugugu ggaggacacc 3900

cugaaccccc cgcuuucaaa caaguuuuca aauuguuuga ggucaggauu ucucaaacug 3960

auuccuuucu uugcauauga guauuugaaa auaaauauuu ucccagaaua uaaauaaauc 4020

aucacaugau uauuuuaacu augcuagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaa 4148

<210> 73

<211> 4157

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的γ S蛋白mRNA

<400> 73

gagugcuccc cauccaacua aacugucccu cuguccgaac uaaacugcac ugucccagca 60

ccauguucgu guuccuggug cugcugcccc uggugagcuc ccagugcgug aacuuuacaa 120

acagaacaca gcugcccucc gccuacacaa acagcuucac caggggcgug uacuaccccg 180

auaaggucuu ucgguccagc gugcugcaca gcacccagga ucuguuccug ccuuucuuca 240

gcaacgugac augguuucac gccauccacg ugagcgggac aaacggcacc aagcgguucg 300

auaacccagu gcugcccuuu aacgaugggg uguacuucgc cagcacagag aaguccaaca 360

ucaucagggg cuggauuuuc ggcaccaccc ucgauuccaa gacacagucc cugcugaucg 420

ugaacaacgc cacaaacgug gucauuaagg ugugcgaguu ccaguuuugc aacuacccau 480

uccugggcgu guacuaccac aagaacaaca aguccuggau ggagagcgag uucagggucu 540

acuccuccgc caacaacugc accuucgagu acgugagcca gcccuuccug auggaucugg 600

agggcaagca ggggaacuuc aagaaccuga gcgaguucgu guucaagaac auugacggcu 660

acuuuaagau cuacaguaag cacacaccua ucaaccuggu gcgggaccug ccucagggcu 720

ucuccgcccu cgagccacug guggaucugc caaucggcau uaacaucacc agguuccaga 780

cacugcuggc ccugcacagg agcuaccuga cuccaggcga uagcuccagc ggguggacag 840

ccggggccgc cgccuacuac gugggcuacc ugcagcccag aaccuuucug cugaaguaca 900

acgagaacgg gaccaucacc gaugccgugg auugcgcccu ggacccccug agcgagacca 960

agugcacucu caaguccuuc accguggaga agggcaucua ccagaccagc aacuuccggg 1020

uccagcccac agaguccauc gugagguucc ccaacaucac caaccucugc cccuucggcg 1080

agguguucaa cgccaccagg uuugccagcg uguacgccug gaacaggaag aggaucucca 1140

acugcguggc cgauuacagc gugcuguaca acuccgccuc cuucagcacc uucaagugcu 1200

acggcgugag cccuaccaag cuuaacgauc ugugcuuuac aaacguguac gccgauagcu 1260

uugugauccg gggggacgag gugaggcaga uugcccccgg ccagacaggg accaucgccg 1320

auuacaacua caagcugccc gaugacuuca ccgggugcgu gauugccugg aacagcaaca 1380

accucgauag caaggucggg gggaacuaca acuaccugua caggcuguuu agaaagucca 1440

accucaagcc uuucgagcgg gauauuagca cugagaucua ccaggccggg agcacacccu 1500

gcaacggggu gaagggcuuc aacugcuacu uuccccugca gagcuacggc uuccagccaa 1560

cauacggcgu gggguaccag cccuaccggg ugguggugcu gagcuucgag cugcugcacg 1620

ccccugccac cgugugcggc cccaagaaaa gcacuaaccu ggugaagaac aagugcguca 1680

acuucaacuu uaacggccug accggcacag gggugcugac cgaguccaac aagaaguucc 1740

ugcccuucca gcaguucggc cgggacaucg ccgauaccac ugacgccgug agggaccccc 1800

agacccugga gauccuggac auuacacccu guagcuucgg cggggucagc gugaucacac 1860

ccggcaccaa cacauccaac cagguggccg ugcuguacca gggcgugaac ugcaccgagg 1920

ugcccgucgc cauccacgcc gaccagcuga cacccacaug gaggguguac agcacaggga 1980

gcaacguguu ccagaccagg gccgggugcc ugaucggcgc cgaguacgug aacaacuccu 2040

acgagugcga cauccccauc ggggccggca uuugcgccuc cuaccagacc cagaccaaca 2100

gcccccggcg ggccaggagc guggccagcc agagcaucau ugccuacaca augucucugg 2160

gcgccgagaa cagcguggcc uacuccaaca acucuaucgc uauccccacc aacuucacca 2220

ucagcgugac cacagagauc cugccugugu ccaugaccaa gaccagcgug gacugcacca 2280

uguacaucug cggcgauucc accgagugcu ccaaccugcu gcugcaguac ggcagcuucu 2340

gcacccagcu gaauagagcc cugacaggga ucgccgugga acaggacaag aacacccaag 2400

agguguucgc ccaagugaag cagaucuaca agaccccucc uaucaaggac uucggcggcu 2460

ucaauuucag ccagauucug cccgauccua gcaagcccag caagcggagc uucaucgagg 2520

accugcuguu caacaaagug acacuggccg acgccggcuu caucaagcag uauggcgauu 2580

gucugggcga cauugccgcc agggaucuga uuugcgccca gaaguuuaac ggacugacag 2640

ugcugccucc ucugcugacc gaugagauga ucgcccagua cacaucugcc cugcuggccg 2700

gcacaaucac aagcggcugg acauuuggag caggcgccgc ucugcagauc cccuuugcua 2760

ugcagauggc cuaccgguuc aacggcaucg gagugaccca gaaugugcug uacgagaacc 2820

agaagcugau cgccaaccag uucaacagcg ccaucggcaa gauccaggac agccugagca 2880

gcacagcaag cgcccuggga aagcugcagg acguggucaa ccagaaugcc caggcacuga 2940

acacccuggu caagcagcug uccuccaacu ucggcgccau cagcucugug cugaacgaua 3000

uccugagcag acuggacccu ccugaggccg aggugcagau cgacagacug aucacaggca 3060

gacugcagag ccuccagaca uacgugaccc agcagcugau cagagccgcc gagauuagag 3120

ccucugccaa ucuggccgcc aucaagaugu cugagugugu gcugggccag agcaagagag 3180

uggacuuuug cggcaagggc uaccaccuga ugagcuuccc ucagucugcc ccucacggcg 3240

ugguguuucu gcacgugaca uaugugcccg cucaagagaa gaauuucacc accgcuccag 3300

ccaucugcca cgacggcaaa gcccacuuuc cuagagaagg cguguucgug uccaacggca 3360

cccauugguu cgugacacag cggaacuucu acgagcccca gaucaucacc accgacaaca 3420

ccuucguguc uggcaacugc gacgucguga ucggcauugu gaacaauacc guguacgacc 3480

cucugcagcc cgagcuggac agcuucaaag aggaacugga caaguacuuu aagaaccaca 3540

caagccccga cguggaccug ggcgauauca gcggaaucaa ugccagcuuc gugaacaucc 3600

agaaagagau cgaccggcug aacgaggugg ccaagaaucu gaacgagagc cugaucgacc 3660

ugcaagaacu ggggaaguac gagcaguaca ucaaguggcc cugguacauc uggcugggcu 3720

uuaucgccgg acugauugcc aucgugaugg ucacaaucau gcuguguugc augaccagcu 3780

gcuguagcug ccugaagggc uguuguagcu guggcagcug cugcaaguuc gacgaggacg 3840

auucugagcc cgugcugaag ggcgugaaac ugcacuacac augaugacuc gaggugugug 3900

gaggacaccc ugaacccccc gcuuucaaac aaguuuucaa auuguuugag gucaggauuu 3960

cucaaacuga uuccuuucuu ugcauaugag uauuugaaaa uaaauauuuu cccagaauau 4020

aaauaaauca ucacaugauu auuuuaacua ugcuagcaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaaaa aaaaaaa 4157

<210> 74

<211> 4151

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的δ变体S蛋白mRNA

<400> 74

gagugcuccc cauccaacua aacugucccu cuguccgaac uaaacugcac ugucccagca 60

ccauguucgu guuccuggug cugcugccuc ugguguccag ccagugugug aaccugagaa 120

ccagaacaca gcugccucca gccuacacca acagcuuuac cagaggcgug uacuaccccg 180

acaagguguu cagauccagc gugcugcacu cuacccagga ccuguuccug ccuuucuuca 240

gcaacgugac cugguuccac gccauccacg uguccggcac caauggcacc aagagauucg 300

acaaccccgu gcugcccuuc aacgacgggg uguacuuugc cagcaccgag aaguccaaca 360

ucaucagagg cuggaucuuc ggcaccacac uggacagcaa gacccagagc cugcugaucg 420

ugaacaacgc caccaacgug gucaucaaag ugugcgaguu ccaguucugc aacgaccccu 480

uccuggacgu cuacuaccac aagaacaaca agagcuggau ggaaagcggc guguacagca 540

gcgccaacaa cugcaccuuc gaguacgugu cccagccuuu ccugauggac cuggaaggca 600

agcagggcaa cuucaagaac cugcgcgagu ucguguuuaa gaacaucgac ggcuacuuca 660

agaucuacag caagcacacc ccuaucaacc ucgugcggga ucugccucag ggcuucucug 720

cucuggaacc ccugguggau cugcccaucg gcaucaacau cacccgguuu cagacacugc 780

uggcccugca cagaagcuac cugacaccug gcgauagcag cagcggaugg acagcuggug 840

ccgccgcuua cuaugugggc uaccugcagc cuagaaccuu ccugcugaag uacaacgaga 900

acggcaccau caccgacgcc guggauugug cucuggaucc ucugagcgag acaaagugca 960

cccugaaguc cuucaccgug gaaaagggca ucuaccagac cagcaacuuc cgggugcagc 1020

ccaccgaauc caucgugcgg uuccccaaua ucaccaaucu gugccccuuc ggcgaggugu 1080

ucaaugccac cagauucgcc ucuguguacg ccuggaaccg gaagcggauc agcaauugcg 1140

uggccgacua cuccgugcug uacaacuccg ccagcuucag caccuucaag ugcuacggcg 1200

uguccccuac caagcugaac gaccugugcu ucacaaacgu guacgccgac agcuucguga 1260

uccggggaga ugaagugcgg cagauugccc cuggacagac aggcaagauc gccgacuaca 1320

acuacaagcu gcccgacgac uucaccggcu gugugauugc cuggaacagc aacaaccugg 1380

acuccaaagu cggcggcaac uacaauuacc gguaccggcu guuccggaag uccaaucuga 1440

agcccuucga gcgggacauc uccaccgaga ucuaucaggc cggcagcaag ccuuguaacg 1500

gcguggaagg cuucaacugc uacuucccac ugcaguccua cggcuuucag cccacaaaug 1560

gcgugggcua ucagcccuac agaguggugg ugcugagcuu cgaacugcug caugccccug 1620

ccacagugug cggcccuaag aaaagcacca aucucgugaa gaacaaaugc gugaacuuca 1680

acuucaacgg ccugaccggc accggcgugc ugacagagag caacaagaag uuccugccau 1740

uccagcaguu uggccgggau aucgccgaua ccacagacgc cguuagagau ccccagacac 1800

uggaaauccu ggacaucacc ccuugcagcu ucggcggagu gucugugauc accccuggca 1860

ccaacaccag caaucaggug gcagugcugu accagggcgu gaacuguacc gaagugcccg 1920

uggccauuca cgccgaucag cugacaccua cauggcgggu guacuccacc ggcagcaaug 1980

uguuucagac cagagccggc ugucugaucg gagccgagca cgugaacaau agcuacgagu 2040

gcgacauccc caucggcgcu ggaaucugcg ccagcuacca gacacagaca aacagccggc 2100

ggagagccag aagcguggcc agccagagca ucauugccua cacaaugucu cugggcgccg 2160

agaacagcgu ggccuacucc aacaacucua ucgcuauccc caccaacuuc accaucagcg 2220

ugaccacaga gauccugccu guguccauga ccaagaccag cguggacugc accauguaca 2280

ucugcggcga uuccaccgag ugcuccaacc ugcugcugca guacggcagc uucugcaccc 2340

agcugaauag agcccugaca gggaucgccg uggaacagga caagaacacc caagaggugu 2400

ucgcccaagu gaagcagauc uacaagaccc cuccuaucaa ggacuucggc ggcuucaauu 2460

ucagccagau ucugcccgau ccuagcaagc ccagcaagcg gagcuucauc gaggaccugc 2520

uguucaacaa agugacacug gccgacgccg gcuucaucaa gcaguauggc gauugucugg 2580

gcgacauugc cgccagggau cugauuugcg cccagaaguu uaacggacug acagugcugc 2640

cuccucugcu gaccgaugag augaucgccc aguacacauc ugcccugcug gccggcacaa 2700

ucacaagcgg cuggacauuu ggagcaggcg ccgcucugca gauccccuuu gcuaugcaga 2760

uggccuaccg guucaacggc aucggaguga cccagaaugu gcuguacgag aaccagaagc 2820

ugaucgccaa ccaguucaac agcgccaucg gcaagaucca ggacagccug agcagcacag 2880

caagcgcccu gggaaagcug cagaacgugg ucaaccagaa ugcccaggca cugaacaccc 2940

uggucaagca gcuguccucc aacuucggcg ccaucagcuc ugugcugaac gauauccuga 3000

gcagacugga cccuccugag gccgaggugc agaucgacag acugaucaca ggcagacugc 3060

agagccucca gacauacgug acccagcagc ugaucagagc cgccgagauu agagccucug 3120

ccaaucuggc cgccaccaag augucugagu gugugcuggg ccagagcaag agaguggacu 3180

uuugcggcaa gggcuaccac cugaugagcu ucccucaguc ugccccucac ggcguggugu 3240

uucugcacgu gacauaugug cccgcucaag agaagaauuu caccaccgcu ccagccaucu 3300

gccacgacgg caaagcccac uuuccuagag aaggcguguu cguguccaac ggcacccauu 3360

gguucgugac acagcggaac uucuacgagc cccagaucau caccaccgac aacaccuucg 3420

ugucuggcaa cugcgacguc gugaucggca uugugaacaa uaccguguac gacccucugc 3480

agcccgagcu ggacagcuuc aaagaggaac uggacaagua cuuuaagaac cacacaagcc 3540

ccgacgugga ccugggcgau aucagcggaa ucaaugccag cgucgugaac auccagaaag 3600

agaucgaccg gcugaacgag guggccaaga aucugaacga gagccugauc gaccugcaag 3660

aacuggggaa guacgagcag uacaucaagu ggcccuggua caucuggcug ggcuuuaucg 3720

ccggacugau ugccaucgug auggucacaa ucaugcugug uugcaugacc agcugcugua 3780

gcugccugaa gggcuguugu agcuguggca gcugcugcaa guucgacgag gacgauucug 3840

agcccgugcu gaagggcgug aaacugcacu acacaugaug acucgaggug uguggaggac 3900

acccugaacc ccccgcuuuc aaacaaguuu ucaaauuguu ugaggucagg auuucucaaa 3960

cugauuccuu ucuuugcaua ugaguauuug aaaauaaaua uuuucccaga auauaaauaa 4020

aucaucacau gauuauuuua acuaugcuag caaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaaaa a 4151

<210> 75

<211> 4157

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的ε变体S蛋白mRNA

<400> 75

gagugcuccc cauccaacua aacugucccu cuguccgaac uaaacugcac ugucccagca 60

ccauguucgu guuccuggug cugcugccuc ugguguccau ccagugugug aaccugacca 120

ccagaacaca gcugccucca gccuacacca acagcuuuac cagaggcgug uacuaccccg 180

acaagguguu cagauccagc gugcugcacu cuacccagga ccuguuccug ccuuucuuca 240

gcaacgugac cugguuccac gccauccacg uguccggcac caauggcacc aagagauucg 300

acaaccccgu gcugcccuuc aacgacgggg uguacuuugc cagcaccgag aaguccaaca 360

ucaucagagg cuggaucuuc ggcaccacac uggacagcaa gacccagagc cugcugaucg 420

ugaacaacgc caccaacgug gucaucaaag ugugcgaguu ccaguucugc aacgaccccu 480

uccugggcgu cuacuaccac aagaacaaca agagcugcau ggaaagcgag uuccgggugu 540

acagcagcgc caacaacugc accuucgagu acguguccca gccuuuccug auggaccugg 600

aaggcaagca gggcaacuuc aagaaccugc gcgaguucgu guuuaagaac aucgacggcu 660

acuucaagau cuacagcaag cacaccccua ucaaccucgu gcgggaucug ccucagggcu 720

ucucugcucu ggaaccccug guggaucugc ccaucggcau caacaucacc cgguuucaga 780

cacugcuggc ccugcacaga agcuaccuga caccuggcga uagcagcagc ggauggacag 840

cuggugccgc cgcuuacuau gugggcuacc ugcagccuag aaccuuccug cugaaguaca 900

acgagaacgg caccaucacc gacgccgugg auugugcucu ggauccucug agcgagacaa 960

agugcacccu gaaguccuuc accguggaaa agggcaucua ccagaccagc aacuuccggg 1020

ugcagcccac cgaauccauc gugcgguucc ccaauaucac caaucugugc cccuucggcg 1080

agguguucaa ugccaccaga uucgccucug uguacgccug gaaccggaag cggaucagca 1140

auugcguggc cgacuacucc gugcuguaca acuccgccag cuucagcacc uucaagugcu 1200

acggcguguc cccuaccaag cugaacgacc ugugcuucac aaacguguac gccgacagcu 1260

ucgugauccg gggagaugaa gugcggcaga uugccccugg acagacaggc aagaucgccg 1320

acuacaacua caagcugccc gacgacuuca ccggcugugu gauugccugg aacagcaaca 1380

accuggacuc caaagucggc ggcaacuaca auuaccgcua ccggcuguuc cggaagucca 1440

aucugaagcc cuucgagcgg gacaucucca ccgagaucua ucaggccggc agcaccccuu 1500

guaacggcgu ggaaggcuuc aacugcuacu ucccacugca guccuacggc uuucagccca 1560

caaauggcgu gggcuaucag cccuacagag ugguggugcu gagcuucgaa cugcugcaug 1620

ccccugccac agugugcggc ccuaagaaaa gcaccaaucu cgugaagaac aaaugcguga 1680

acuucaacuu caacggccug accggcaccg gcgugcugac agagagcaac aagaaguucc 1740

ugccauucca gcaguuuggc cgggauaucg ccgauaccac agacgccguu agagaucccc 1800

agacacugga aauccuggac aucaccccuu gcagcuucgg cggagugucu gugaucaccc 1860

cuggcaccaa caccagcaau cagguggcag ugcuguacca gggcgugaac uguaccgaag 1920

ugcccguggc cauucacgcc gaucagcuga caccuacaug gcggguguac uccaccggca 1980

gcaauguguu ucagaccaga gccggcuguc ugaucggagc cgagcacgug aacaauagcu 2040

acgagugcga cauccccauc ggcgcuggaa ucugcgccag cuaccagaca cagacaaaca 2100

gcccucggag agccagaagc guggccagcc agagcaucau ugccuacaca augucucugg 2160

gcgccgagaa cagcguggcc uacuccaaca acucuaucgc uauccccacc aacuucacca 2220

ucagcgugac cacagagauc cugccugugu ccaugaccaa gaccagcgug gacugcacca 2280

uguacaucug cggcgauucc accgagugcu ccaaccugcu gcugcaguac ggcagcuucu 2340

gcacccagcu gaauagagcc cugacaggga ucgccgugga acaggacaag aacacccaag 2400

agguguucgc ccaagugaag cagaucuaca agaccccucc uaucaaggac uucggcggcu 2460

ucaauuucag ccagauucug cccgauccua gcaagcccag caagcggagc uucaucgagg 2520

accugcuguu caacaaagug acacuggccg acgccggcuu caucaagcag uauggcgauu 2580

gucugggcga cauugccgcc agggaucuga uuugcgccca gaaguuuaac ggacugacag 2640

ugcugccucc ucugcugacc gaugagauga ucgcccagua cacaucugcc cugcuggccg 2700

gcacaaucac aagcggcugg acauuuggag caggcgccgc ucugcagauc cccuuugcua 2760

ugcagauggc cuaccgguuc aacggcaucg gagugaccca gaaugugcug uacgagaacc 2820

agaagcugau cgccaaccag uucaacagcg ccaucggcaa gauccaggac agccugagca 2880

gcacagcaag cgcccuggga aagcugcagg acguggucaa ccagaaugcc caggcacuga 2940

acacccuggu caagcagcug uccuccaacu ucggcgccau cagcucugug cugaacgaua 3000

uccugagcag acuggacccu ccugaggccg aggugcagau cgacagacug aucacaggca 3060

gacugcagag ccuccagaca uacgugaccc agcagcugau cagagccgcc gagauuagag 3120

ccucugccaa ucuggccgcc accaagaugu cugagugugu gcugggccag agcaagagag 3180

uggacuuuug cggcaagggc uaccaccuga ugagcuuccc ucagucugcc ccucacggcg 3240

ugguguuucu gcacgugaca uaugugcccg cucaagagaa gaauuucacc accgcuccag 3300

ccaucugcca cgacggcaaa gcccacuuuc cuagagaagg cguguucgug uccaacggca 3360

cccauugguu cgugacacag cggaacuucu acgagcccca gaucaucacc accgacaaca 3420

ccuucguguc uggcaacugc gacgucguga ucggcauugu gaacaauacc guguacgacc 3480

cucugcagcc cgagcuggac agcuucaaag aggaacugga caaguacuuu aagaaccaca 3540

caagccccga cguggaccug ggcgauauca gcggaaucaa ugccagcguc gugaacaucc 3600

agaaagagau cgaccggcug aacgaggugg ccaagaaucu gaacgagagc cugaucgacc 3660

ugcaagaacu ggggaaguac gagcaguaca ucaaguggcc cugguacauc uggcugggcu 3720

uuaucgccgg acugauugcc aucgugaugg ucacaaucau gcuguguugc augaccagcu 3780

gcuguagcug ccugaagggc uguuguagcu guggcagcug cugcaaguuc gacgaggacg 3840

auucugagcc cgugcugaag ggcgugaaac ugcacuacac augaugacuc gaggugugug 3900

gaggacaccc ugaacccccc gcuuucaaac aaguuuucaa auuguuugag gucaggauuu 3960

cucaaacuga uuccuuucuu ugcauaugag uauuugaaaa uaaauauuuu cccagaauau 4020

aaauaaauca ucacaugauu auuuuaacua ugcuagcaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaaaa aaaaaaa 4157

<210> 76

<211> 4148

<212> RNA

<213> 人工

<220>

<223> 含有5'-UTR、3'-UTR及多A的ο变体S蛋白mRNA

<400> 76

gagugcuccc cauccaacua aacugucccu cuguccgaac uaaacugcac ugucccagca 60

ccauguucgu guuccuggug cugcugccuc ugguguccag ccagugugug aaccugacca 120

ccagaacaca gcugccucca gccuacacca acagcuuuac cagaggcgug uacuaccccg 180

acaagguguu cagauccagc gugcugcacu cuacccagga ccuguuccug ccuuucuuca 240

gcaacgugac cugguuccac gugaucuccg gcaccaaugg caccaagaga uucgacaacc 300

ccgugcugcc cuucaacgac gggguguacu uugccagcau cgagaagucc aacaucauca 360

gaggcuggau cuucggcacc acacuggaca gcaagaccca gagccugcug aucgugaaca 420

acgccaccaa cguggucauc aaagugugcg aguuccaguu cugcaacgac cccuuccugg 480

accacaagaa caacaagagc uggauggaaa gcgaguuccg gguguacagc agcgccaaca 540

acugcaccuu cgaguacgug ucccagccuu uccugaugga ccuggaaggc aagcagggca 600

acuucaagaa ccugcgcgag uucguguuua agaacaucga cggcuacuuc aagaucuaca 660

gcaagcacac cccuaucauc gugcgggaac cugaagaucu gccucagggc uucucugcuc 720

uggaaccccu gguggaucug cccaucggca ucaacaucac ccgguuucag acacugcugg 780

cccugcacag aagcuaccug acaccuggcg auagcagcag cggauggaca gcuggugccg 840

ccgcuuacua ugugggcuac cugcagccua gaaccuuccu gcugaaguac aacgagaacg 900

gcaccaucac cgacgccgug gauugugcuc uggauccucu gagcgagaca aagugcaccc 960

ugaaguccuu caccguggaa aagggcaucu accagaccag caacuuccgg gugcagccca 1020

ccgaauccau cgugcgguuc cccaauauca ccaaucugug ccccuucgac gagguguuca 1080

augccaccag auucgccucu guguacgccu ggaaccggaa gcggaucagc aauugcgugg 1140

ccgacuacuc cgugcuguac aaccuggccc ccuucuucac cuucaagugc uacggcgugu 1200

ccccuaccaa gcugaacgac cugugcuuca caaacgugua cgccgacagc uucgugaucc 1260

ggggagauga agugcggcag auugccccug gacagacagg caacaucgcc gacuacaacu 1320

acaagcugcc cgacgacuuc accggcugug ugauugccug gaacagcaac aagcuggacu 1380

ccaaagucuc cggcaacuac aauuaccugu accggcuguu ccggaagucc aaucugaagc 1440

ccuucgagcg ggacaucucc accgagaucu aucaggccgg caacaagccu uguaacggcg 1500

uggccggcuu caacugcuac uucccacugc gguccuacuc cuuucggccc acauauggcg 1560

ugggccauca gcccuacaga gugguggugc ugagcuucga acugcugcau gccccugcca 1620

cagugugcgg cccuaagaaa agcaccaauc ucgugaagaa caaaugcgug aacuucaacu 1680

ucaacggccu gaagggcacc ggcgugcuga cagagagcaa caagaaguuc cugccauucc 1740

agcaguuugg ccgggauauc gccgauacca cagacgccgu uagagauccc cagacacugg 1800

aaauccugga caucaccccu ugcagcuucg gcggaguguc ugugaucacc ccuggcacca 1860

acaccagcaa ucagguggca gugcuguacc agggcgugaa cuguaccgaa gugcccgugg 1920

ccauucacgc cgaucagcug acaccuacau ggcgggugua cuccaccggc agcaaugugu 1980

uucagaccag agccggcugu cugaucggag ccgaguacgu gaacaauagc uacgagugcg 2040

acauccccau cggcgcugga aucugcgcca gcuaccagac acagacaaag agccaucgga 2100

gagccagaag cguggccagc cagagcauca uugccuacac aaugucucug ggcgccgaga 2160

acagcguggc cuacuccaac aacucuaucg cuauccccac caacuucacc aucagcguga 2220

ccacagagau ccugccugug uccaugacca agaccagcgu ggacugcacc auguacaucu 2280

gcggcgauuc caccgagugc uccaaccugc ugcugcagua cggcagcuuc ugcacccagc 2340

ugaagagagc ccugacaggg aucgccgugg aacaggacaa gaacacccaa gagguguucg 2400

cccaagugaa gcagaucuac aagaccccuc cuaucaagua cuucggcggc uucaauuuca 2460

gccagauucu gcccgauccu agcaagccca gcaagcggag cuucaucgag gaccugcugu 2520

ucaacaaagu gacacuggcc gacgccggcu ucaucaagca guauggcgau ugucugggcg 2580

acauugccgc cagggaucug auuugcgccc agaaguuuaa gggacugaca gugcugccuc 2640

cucugcugac cgaugagaug aucgcccagu acacaucugc ccugcuggcc ggcacaauca 2700

caagcggcug gacauuugga gcaggcgccg cucugcagau ccccuuugcu augcagaugg 2760

ccuaccgguu caacggcauc ggagugaccc agaaugugcu guacgagaac cagaagcuga 2820

ucgccaacca guucaacagc gccaucggca agauccagga cagccugagc agcacagcaa 2880

gcgcccuggg aaagcugcag gacgugguca accacaaugc ccaggcacug aacacccugg 2940

ucaagcagcu guccuccaag uucggcgcca ucagcucugu gcugaacgau aucuucagca 3000

gacuggaccc uccugaggcc gaggugcaga ucgacagacu gaucacaggc agacugcaga 3060

gccuccagac auacgugacc cagcagcuga ucagagccgc cgagauuaga gccucugcca 3120

aucuggccgc caccaagaug ucugagugug ugcugggcca gagcaagaga guggacuuuu 3180

gcggcaaggg cuaccaccug augagcuucc cucagucugc cccucacggc gugguguuuc 3240

ugcacgugac auaugugccc gcucaagaga agaauuucac caccgcucca gccaucugcc 3300

acgacggcaa agcccacuuu ccuagagaag gcguguucgu guccaacggc acccauuggu 3360

ucgugacaca gcggaacuuc uacgagcccc agaucaucac caccgacaac accuucgugu 3420

cuggcaacug cgacgucgug aucggcauug ugaacaauac cguguacgac ccucugcagc 3480

ccgagcugga cagcuucaaa gaggaacugg acaaguacuu uaagaaccac acaagccccg 3540

acguggaccu gggcgauauc agcggaauca augccagcgu cgugaacauc cagaaagaga 3600

ucgaccggcu gaacgaggug gccaagaauc ugaacgagag ccugaucgac cugcaagaac 3660

uggggaagua cgagcaguac aucaaguggc ccugguacau cuggcugggc uuuaucgccg 3720

gacugauugc caucgugaug gucacaauca ugcuguguug caugaccagc ugcuguagcu 3780

gccugaaggg cuguuguagc uguggcagcu gcugcaaguu cgacgaggac gauucugagc 3840

ccgugcugaa gggcgugaaa cugcacuaca caugaugacu cgaggugugu ggaggacacc 3900

cugaaccccc cgcuuucaaa caaguuuuca aauuguuuga ggucaggauu ucucaaacug 3960

auuccuuucu uugcauauga guauuugaaa auaaauauuu ucccagaaua uaaauaaauc 4020

aucacaugau uauuuuaacu augcuagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4080

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4140

aaaaaaaa 4148

<210> 77

<211> 57

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 77

ccctctgtcc ctctgaccct gcactgtccc agcaccatgt tcgtgttcct ggtgctg 57

<210> 78

<211> 71

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 78

atataagctt taatacgact cactataagt cctccccatc ctctccctct gtccctctgt 60

ccctctgacc c 71

<210> 79

<211> 59

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 79

cctctccctc tgtccctctc ctgcactgtc ccagcaccat gttcgtgttc ctggtgctg 59

<210> 80

<211> 70

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 80

atataagctt taatacgact cactataagt cctcccccgt ccctctgaat cctctccctc 60

tgtccctctc 70

<210> 81

<211> 65

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 81

ccctctttcc ctctgtccct cttacccttc actttcccag caccatgttc gtgttcctgg 60

tgctg 65

<210> 82

<211> 65

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 82

atataagctt taatacgact cactataagt cctccccatc ctctccctct ttccctctgt 60

ccctc 65

<210> 83

<211> 57

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 83

ccctctgtcc ctctgaccct gcactgtccc agcaccatgt tcgtgttcct ggtgctg 57

<210> 84

<211> 71

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 84

atataagctt taatacgact cactataagt cctccccatt ttttttttct gtccctctgt 60

ccctctgacc c 71

<210> 85

<211> 57

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 85

ccctctgtcc ctctgaccct gcactgtccc agcaccatgt tcgtgttcct ggtgctg 57

<210> 86

<211> 71

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 86

atataagctt taatacgact cactataagt cctccccatc caactaaact gtccctctgt 60

ccctctgacc c 71

<210> 87

<211> 57

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 87

ccctctgtcc caactaaact gcactgtccc agcaccatgt tcgtgttcct ggtgctg 57

<210> 88

<211> 74

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 88

atataagctt taatacgact cactataagt cctccccatc caactaaact gtccctctgt 60

cccaactaaa ctgc 74

<210> 89

<211> 63

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 89

ctctgtccct ctgtcccaac taaactgcac tgtcccagca ccatgttcgt gttcctggtg 60

ctg 63

<210> 90

<211> 67

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 90

atataagctt taatacgact cactataagt cctccccata actaaactct gtccctctgt 60

cccaact 67

<210> 91

<211> 61

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 91

ctgtccctct gtcccaacta aactgcactg tcccagcacc atgttcgtgt tcctggtgct 60

g 61

<210> 92

<211> 71

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 92

atataagctt taatacgact cactataagt cctccccata actaaaaact gtccctctgt 60

cccaactaaa c 71

<210> 93

<211> 61

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 93

ctgtccctct atcccaacta aactgcactg ttccagcacc atgttcgtgt tcctggtgct 60

g 61

<210> 94

<211> 73

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 94

atataagctt taatacgact cactataagt cctccccatc caactaaact gtccctctat 60

cccaactaaa ctg 73

<210> 95

<211> 74

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 95

atataagctt taatacgact cactatagag tcctccccat ccaactaaac tgtccctcta 60

tcccaactaa actg 74

<210> 96

<211> 61

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 96

ctgtccctct gtccgaacta aactgcactg tcccagcacc atgttcgtgt tcctggtgct 60

g 61

<210> 97

<211> 71

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 97

atataagctt taatacgact cactataagt gctccccatc caactaaact gtccctctgt 60

ccgaactaaa c 71

<210> 98

<211> 61

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 98

ctgtccttct gtcccaacta aactgcactg tcccagcacc atgttcgtgt tcctggtgct 60

g 61

<210> 99

<211> 73

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 99

atataagctt taatacgact cactataagt cctacccatc caactaaact gtccttctgt 60

cccaactaaa ctg 73

<210> 100

<211> 19

<212> DNA

<213> 人工

<220>

<223> 引子

<400> 100

gccacgcaat tgctgatcc 19

<210> 101

<211> 100

<212> RNA

<213> 人工

<220>

<223> 多A RNA

<400> 101

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 60

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 100

<210> 102

<211> 181

<212> RNA

<213> 人工

<220>

<223> 具有限制位置的3'-UTR

<400> 102

cucgagccac acccccauuc ccccacucca gauaaagcuu caguuauauc ucacgugucu 60

ggaguucuuu gccaagaggg agaggcugaa auccccagcc gccucaccug cagcucagcu 120

ccauccccuc accuguuccc accgcauuuu cuccuggcgu ucgccugcua guguggcuag 180

c 181

<210> 103

<211> 198

<212> RNA

<213> 人工

<220>

<223> 具有限制位置的3'-UTR

<400> 103

cucgagccac acccccauuc ccccacucca gauaaagcuu caguuauauc ucacgugucu 60

ggaguucuuu gccaagaggg agaggcugaa auccccagcc gccucaccug cagcucagcu 120

ccauccucca cccccccauc uccccucacc uguucccacc gcauuuucuc cuggcguucg 180

ccugcuagug uggcuagc 198

<210> 104

<211> 188

<212> RNA

<213> 人工

<220>

<223> 具有限制位置的3'-UTR

<400> 104

cucgagccac acccccauuc ccccacucca gauaaagcuu caguuauauc ucacgugucu 60

ggaguucuuu gccaagaggg agaggcugaa auccccagcc gccucaccug cagcucagcu 120

ccauccuugg uuuccucacc uguucccacc gcauuuucuc cuggcguucg ccugcuagug 180

uggcuagc 188

<210> 105

<211> 162

<212> RNA

<213> 人工

<220>

<223> 具有限制位置的3'-UTR

<400> 105

cucgaggugu gacccugaac cccccgcuuu caaacaaguu uucaaauugu uugaggucag 60

gauuucucaa acugauuccu uucuuugcau augaguauuu gaaaauaaau auuuucccag 120

aauauaaaua aaucaucaca ugauuauuuu aacuaugcua gc 162

<210> 106

<211> 179

<212> RNA

<213> 人工

<220>

<223> 具有限制位置的3'-UTR

<400> 106

cucgaggugu guccaccccc ccaucuccac ccugaacccc ccgcuuucaa acaaguuuuc 60

aaauuguuug aggucaggau uucucaaacu gauuccuuuc uuugcauaug aguauuugaa 120

aauaaauauu uucccagaau auaaauaaau caucacauga uuauuuuaac uaugcuagc 179

<210> 107

<211> 169

<212> RNA

<213> 人工

<220>

<223> 具有限制位置的3'-UTR

<400> 107

cucgaggugu guugguuuac ccugaacccc ccgcuuucaa acaaguuuuc aaauuguuug 60

aggucaggau uucucaaacu gauuccuuuc uuugcauaug aguauuugaa aauaaauauu 120

uucccagaau auaaauaaau caucacauga uuauuuuaac uaugcuagc 169

<210> 108

<211> 170

<212> RNA

<213> 人工

<220>

<223> 具有限制位置的3'-UTR

<400> 108

cucgaggugu guggaggaca cccugaaccc cccgcuuuca aacaaguuuu caaauuguuu 60

gaggucagga uuucucaaac ugauuccuuu cuuugcauau gaguauuuga aaauaaauau 120

uuucccagaa uauaaauaaa ucaucacaug auuauuuuaa cuaugcuagc 170

<210> 109

<211> 181

<212> DNA

<213> 人工

<220>

<223> 编码具有限制位置的3'-UTR的序列

<400> 109

ctcgagccac acccccattc ccccactcca gataaagctt cagttatatc tcacgtgtct 60

ggagttcttt gccaagaggg agaggctgaa atccccagcc gcctcacctg cagctcagct 120

ccatcccctc acctgttccc accgcatttt ctcctggcgt tcgcctgcta gtgtggctag 180

c 181

<210> 110

<211> 198

<212> DNA

<213> 人工

<220>

<223> 编码具有限制位置的3'-UTR的序列

<400> 110

ctcgagccac acccccattc ccccactcca gataaagctt cagttatatc tcacgtgtct 60

ggagttcttt gccaagaggg agaggctgaa atccccagcc gcctcacctg cagctcagct 120

ccatcctcca cccccccatc tcccctcacc tgttcccacc gcattttctc ctggcgttcg 180

cctgctagtg tggctagc 198

<210> 111

<211> 188

<212> DNA

<213> 人工

<220>

<223> 编码具有限制位置的3'-UTR的序列

<400> 111

ctcgagccac acccccattc ccccactcca gataaagctt cagttatatc tcacgtgtct 60

ggagttcttt gccaagaggg agaggctgaa atccccagcc gcctcacctg cagctcagct 120

ccatccttgg tttcctcacc tgttcccacc gcattttctc ctggcgttcg cctgctagtg 180

tggctagc 188

<210> 112

<211> 162

<212> DNA

<213> 人工

<220>

<223> 编码具有限制位置的3'-UTR的序列

<400> 112

ctcgaggtgt gaccctgaac cccccgcttt caaacaagtt ttcaaattgt ttgaggtcag 60

gatttctcaa actgattcct ttctttgcat atgagtattt gaaaataaat attttcccag 120

aatataaata aatcatcaca tgattatttt aactatgcta gc 162

<210> 113

<211> 179

<212> DNA

<213> 人工

<220>

<223> 编码具有限制位置的3'-UTR的序列

<400> 113

ctcgaggtgt gtccaccccc ccatctccac cctgaacccc ccgctttcaa acaagttttc 60

aaattgtttg aggtcaggat ttctcaaact gattcctttc tttgcatatg agtatttgaa 120

aataaatatt ttcccagaat ataaataaat catcacatga ttattttaac tatgctagc 179

<210> 114

<211> 169

<212> DNA

<213> 人工

<220>

<223> 编码具有限制位置的3'-UTR的序列

<400> 114

ctcgaggtgt gttggtttac cctgaacccc ccgctttcaa acaagttttc aaattgtttg 60

aggtcaggat ttctcaaact gattcctttc tttgcatatg agtatttgaa aataaatatt 120

ttcccagaat ataaataaat catcacatga ttattttaac tatgctagc 169

<210> 115

<211> 170

<212> DNA

<213> 人工

<220>

<223> 编码具有限制位置的3'-UTR的序列

<400> 115

ctcgaggtgt gtggaggaca ccctgaaccc cccgctttca aacaagtttt caaattgttt 60

gaggtcagga tttctcaaac tgattccttt ctttgcatat gagtatttga aaataaatat 120

tttcccagaa tataaataaa tcatcacatg attattttaa ctatgctagc 170

Claims

1.一种分离的多核苷酸，其为聚去氧核糖核苷酸，包含：编码非自然发生的5’-非转译区的核苷酸序列、编码3’-非转译区的核苷酸序列或其组合。

2.根据权利要求1的多核苷酸，其中所述5’-非转译区包含与SEQ ID NO:1的核苷酸序列具有70％或以上的序列一致性的核苷酸序列。

3.根据权利要求1的多核苷酸，其中所述3’-非转译区包含与SEQ ID NO:15或20的核苷酸序列具有80％或以上的序列一致性的核苷酸序列。

4.根据权利要求1的多核苷酸，其中编码所述5’-非转译区的所述核苷酸序列选自于SEQ ID NO:22至33的核苷酸序列。

5.根据权利要求1的多核苷酸，其中编码所述3’-非转译区的所述核苷酸序列选自于包含SEQ ID NO:34至40的各核苷酸序列的核苷酸序列。

6.根据权利要求1的多核苷酸，其中编码所述5’-非转译区的所述核苷酸序列更包括可操作地连接至所述5’-非转译区的上游启动子区核苷酸序列。

7.根据权利要求1的多核苷酸，其中编码所述5’-非转译区的所述核苷酸序列包括可转录核苷酸序列或用于导入可转录核苷酸序列的核苷酸序列，且所述可转录核苷酸序列或所述用于导入可转录核苷酸序列的核苷酸序列在编码所述5’-非转译区的核苷酸的下游可操作地连接至所述5’-非转译区。

8.根据权利要求7的多核苷酸，其中所述可转录核苷酸序列为编码多胜肽或RNA的序列。

9.根据权利要求8的多核苷酸，其中所述多胜肽为抗原性多胜肽或治疗性多胜肽。

10.根据权利要求7的多核苷酸，其中所述用于导入可转录核苷酸序列的核苷酸序列为选殖位。

11.根据权利要求7至10中任一项的多核苷酸，其中所述可转录核苷酸序列或所述用于导入可转录核苷酸序列的核苷酸序列在编码所述3’-非转译区的核苷酸的上游可操作地连接至所述3’-非转译区，以及

编码所述3’-非转译区的所述核苷酸序列更包含可操作地连接至所述3’-非转译区的下游多腺苷酸或多腺苷酸附着信号的核苷酸序列。

12.根据权利要求11的多核苷酸，其中编码所述5’-非转译区的所述核苷酸序列包含SEQ ID NO:22或31的核苷酸序列，

编码所述3’-非转译区的所述核苷酸序列包含SEQ ID NO:40的核苷酸序列，以及

所述多腺苷酸的核苷酸序列包含SEQ ID NO:41的核苷酸序列。

13.根据权利要求1的多核苷酸，其中编码所述3’-非转译区的所述核苷酸序列更包含可操作地连接至所述3’-非转译区的下游多腺苷酸或多腺苷酸附着信号的核苷酸序列。

14.根据权利要求1的多核苷酸，其中编码所述3’-非转译区的所述核苷酸序列包括可转录核苷酸序列或用于导入可转录核苷酸序列的核苷酸序列，且所述可转录核苷酸序列或所述用于导入可转录核苷酸序列的核苷酸序列在编码所述3’-非转译区的核苷酸的上游可操作地连接至所述3’-非转译区。

15.根据权利要求1的多核苷酸，其中编码所述5’-非转译区的所述核苷酸序列包含可操作地连接至所述5’-非转译区的上游启动子区核苷酸序列、可操作地连接至所述启动子的可转录核苷酸序列或用于导入可转录核苷酸序列的核苷酸序列；所述可转录核苷酸序列或所述用于导入可转录核苷酸序列的核苷酸序列在编码所述5’-非转译区的所述核苷酸序列的下游可操作地连接至编码所述5’-非转译区的核苷酸序列；以及

编码所述3’-非转译区的所述核苷酸序列包含可操作地连接至所述3’-非转译区的下游多腺苷酸或多腺苷酸附着信号的核苷酸序列，且编码所述3’-非转译区的所述核苷酸序列在编码所述3’-非转译区的所述核苷酸序列的上游可操作地连接至所述可转录核苷酸序列或所述用于导入可转录核苷酸序列的核苷酸序列。

16.根据权利要求15的多核苷酸，其中编码所述5’-非转译区的所述核苷酸序列为SEQID NO:22或SEQ ID NO:31的核苷酸序列，并包含可转录核苷酸序列或可操作地连接至所述启动子的用于导入可转录核苷酸序列的核苷酸序列；所述可转录核苷酸序列或所述用于导入可转录核苷酸序列的核苷酸序列在所述5’-非转译区序列的下游可操作地连接至所述5’-非转译区序列；以及

所述3’-非转译区包含可操作地连接至所述3’-非转译区的下游多腺苷酸或多腺苷酸附着信号的核苷酸序列，且所述3’-非转译区在编码所述3’-非转译区的所述核苷酸序列的上游可操作地连接至所述可转录核苷酸序列或所述用于导入可转录核苷酸序列的核苷酸序列。

17.根据权利要求1至16中任一项的多核苷酸，其中所述多核苷酸为表达构筑体或载体。

18.一种可通过转录获得的RNA，其使用如权利要求1至16中任一项的多核苷酸作为模板。

19.一种分离的多核苷酸，其为多核糖核苷酸，包含：非自然发生的5’-非转译区的核苷酸序列、3’-非转译区的核苷酸序列或其组合。

20.根据权利要求19的多核苷酸，其中所述5’-非转译区包含与SEQ ID NO:1的核苷酸序列具有70％或以上的序列一致性的核苷酸序列。

21.根据权利要求19的多核苷酸，其中所述3’-非转译区包含与SEQ ID NO:15或20的核苷酸序列具有80％或以上的序列一致性的核苷酸序列。

22.根据权利要求19的多核苷酸，其中所述5’-非转译区核苷酸序列包含编码多胜肽的核苷酸序列，且编码多胜肽的所述核苷酸序列在所述5’-非转译区核苷酸的下游可操作地连接至所述5’-非转译区。

23.根据权利要求22的多核苷酸，其中所述多胜肽为抗原性多胜肽或治疗性多胜肽。

24.根据权利要求19的多核苷酸，其中所述3’-非转译区核苷酸序列更包含可操作地连接至所述3’-非转译区的下游多腺苷酸的核苷酸序列。

25.根据权利要求19的多核苷酸，其中所述3’-非转译区核苷酸序列包含编码多胜肽的核苷酸序列，且编码多胜肽的所述核苷酸序列在所述3’-非转译区核苷酸的上游可操作地连接至所述3’-非转译区。

26.根据权利要求19的多核苷酸，其中所述5’-非转译区核苷酸序列包含编码多胜肽的核苷酸序列，且编码多胜肽的所述核苷酸序列在所述5’-非转译区核苷酸的下游可操作地连接至所述5’-非转译区，以及

所述3’-非转译区核苷酸序列包含可操作地连接至所述3’-非转译区的下游多腺苷酸的核苷酸序列，且在所述3’-非转译区核苷酸的上游可操作地连接至所述编码多胜肽的核苷酸序列。

27.根据权利要求26的多核苷酸，其中所述5’-非转译区核苷酸序列包含SEQ ID NO:1或10的核苷酸序列，

所述3’-非转译区核苷酸序列包含SEQ ID NO:20的核苷酸序列，以及

所述多腺苷酸的核苷酸序列包含SEQ ID NO:101的核苷酸序列。

28.根据权利要求27的多核苷酸，其中所述多核苷酸中的至少一U通过N1-甲基-假尿苷取代。

29.根据权利要求28的多核苷酸，其中所述多核苷酸具有任一选自于SEQ ID NO:63至76的核苷酸序列，且所述多核苷酸中的至少一U通过N1-甲基-假尿苷取代。

30.根据权利要求19的多核苷酸，其中所述5’-非转译区或所述3’-非转译区具有增加转译效率、编码多胜肽的核苷酸序列的稳定性或其组合的活性。

31.根据权利要求19的多核苷酸，其中5’端具有5’端帽结构。

32.根据权利要求19的多核苷酸，其中所述多核苷酸包含至少一修饰的核苷酸。

33.根据权利要求32的多核苷酸，其中所述修饰的核苷酸具有至少一通过N1-甲基-假尿苷取代的尿苷。

34.一种将多胜肽递输至受试者的组合物，其中所述组合物包含以如权利要求19至33中任一项的多核苷酸作为活性成分。