TW202223392A - 蛋白質微陣列、其檢測方法、其用途及含有該蛋白質微陣列之試劑盒 - Google Patents
蛋白質微陣列、其檢測方法、其用途及含有該蛋白質微陣列之試劑盒 Download PDFInfo
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Abstract
本發明提供一種蛋白質微陣列、其檢測方法、其用途及含有該蛋白質微陣列之試劑盒。蛋白質微陣列包括表面具有蛋白質陣列區塊之載體,及固定於該蛋白質陣列區塊上之至少一蛋白質,至少一蛋白質包括棘蛋白及核鞘蛋白且可與待測樣本中的第一抗體產生結合。試劑盒用於體外檢測病毒感染,包括蛋白質微陣列及可與第一抗體產生結合之第二抗體。病毒感染之檢測方法包括步驟:分別將血清及第二抗體加入至蛋白質微陣列中,並檢測光學訊號。蛋白質微陣列可用於檢測冠狀病毒及流感病毒,以確定受試者是否受到病毒感染及評估生物製劑阻斷病毒感染之能力。
Description
本發明係有關一種微陣列,尤指一種蛋白質微陣列;本發明亦有關一種檢測方法,尤指一種蛋白質微陣列之檢測方法;本發明亦有關一種用途,尤指一種蛋白質微陣列之用途;以及,本發明亦有關一種試劑盒,尤指一種含有該蛋白質微陣列且用於體外檢測病毒感染之試劑盒。
由病毒所引起之傳染病,例如,由流感病毒或冠狀病毒所引起之急性呼吸道症候群或由嚴重急性呼吸道症候群冠狀病毒所引起之嚴重急性呼吸道症候群,具有高度的傳染力,其主要藉由打噴嚏或咳嗽之飛沫直接傳播為主,或者接觸經病毒感染之汙染物,再觸摸口或鼻而間接感染。因此,倘若經流感病毒或冠狀病毒感染之患者未經準確的檢測,則容易導致傳染病之疫情擴大並蔓延至全世界。
舉例而言,約莫於2019年12月,中國大陸武漢市首次引發嚴重特殊傳染性肺炎之群聚感染,且隨後在中國大陸的其他省市迅速擴散並蔓延至世界各地。截至目前為止,全球確診案例已超過5,000萬例,而死亡案例則已超過100萬例。該嚴重特殊傳染性肺炎亦稱為「2019新型冠病毒疾病」(coronavirus disease 2019, COVID-19),其係由嚴重急性呼吸道症候群冠狀病毒第二型(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2),亦稱為新型冠狀病毒之感染所引起。由於COVID-19疫情已蔓延於全世界且目前疫情依舊嚴峻,因此,為避免COVID-19疫情持續蔓延,針對與罹患COVID-19之患者有接觸史且出現上呼吸道症狀之疑似罹患COVID-19之民眾進行COVID-19檢測已是當務之急。
目前普遍用以快速檢測COVID-19之方式係以鼻腔拭子或咽喉拭子採集受試者之鼻咽腔黏膜之樣本,並利用即時定量聚合酶連鎖反應(real-time polymerase chain reaction, real-time PCR)之核酸檢測方式檢測鼻腔拭子或咽喉拭子中的SARS-CoV-2核糖核酸(SARS-CoV-2 RNA)。然而,以鼻腔拭子或咽喉拭子採集受試者之樣本時,往往會引起受試者之鼻腔或喉嚨不舒服感,導致受試者容易打噴嚏或咳嗽,進而增加SARS-CoV-2傳播以及人傳人之風險。此外,以即時定量聚合酶連鎖反應首次檢測受試者受試者之鼻咽腔黏膜中的SARS-CoV-2 RNA的靈敏度約僅為59%,且須經3次採集樣本並檢測方能確定受試者是否罹患COVID-19。
再者,針對已罹患COVID-19之患者,世界各國目前仍尚未研發出能有效治療已罹患COVID-19之患者的生物製劑。
因此,以即時定量聚合酶連鎖反應檢測受試者是否罹患流感病毒或冠狀病毒具有可能增加病毒傳播之風險、首次檢測之靈敏度不高以及須多次檢測以確定結果等缺點,且能有效阻斷病毒感染之生物製劑尚未被成功地研發。
是以,開發出一種靈敏度高且可快速檢測流感病毒或冠狀病毒感染及評估生物製劑阻斷病毒感染之能力之試劑盒以及病毒感染之檢測方法係本領域亟待解決之問題。
為解決上述現有技術之問題,本發明之目的在於提供一種蛋白質微陣列,透過將來自嚴重急性呼吸道症候群冠狀病毒第二型(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2,亦稱新型冠狀病毒)之棘蛋白及核鞘蛋白固定於蛋白質微陣列之載體上,藉以達到快速地且準確地檢測病毒感染之目的。
本發明之另一目的在於提供一種病毒感染之檢測方法,透過將受試者之血清與該蛋白質微陣列進行反應,可達到快速地且準確地確定受試者是否受冠狀病毒及流感病毒感染之目的。
本發明之又一目的在於提供一種蛋白質微陣列之用途,透過使用該蛋白質微陣列進行檢測,可達到確定受試者是否受冠狀病毒或流感病毒感染或評估諸如受體阻斷劑藥物或單株抗體藥物之生物製劑對於阻斷病毒感染之能力之目的。
本發明之再一目的在於提供一種含有該蛋白質微陣列之試劑盒,透過該蛋白質微陣列及一經螢光標記之第二抗體或經酵素標記之第二抗體,藉以達到快速地且準確地在體外檢測病毒感染之目的。
為了達成上述目的,本發明提供一種蛋白質微陣列,可包括:一載體以及至少一蛋白質。該載體之表面包括數個蛋白質陣列區塊(protein array block);該至少一蛋白質係固定於該蛋白質陣列區塊上,其中該至少一蛋白質係來自一病毒且包括一棘蛋白(spike protein)及一核鞘蛋白(nucleocapsid protein)。該至少一蛋白質包括具有如SEQ ID NO:1所示之胺基酸序列及如SEQ ID NO:4所示之胺基酸序列,且該至少一蛋白質配置用以與一待測樣本中的一第一抗體或一生物製劑產生專一性地結合。
在一具體實施例中,該載體可為一玻璃載體或一尼龍薄膜載體。
在一具體實施例中,該載體之表面可包括一醛基化修飾層或一胺基化修飾層。
在一具體實施例中,該至少一蛋白質進一步可包括一棘蛋白S1結構域(spike protein S1 domain)、一血球凝集素蛋白(hemagglutinin protein)或其組合。
在一具體實施例中,該至少一蛋白質進一步可包括選自由如SEQ ID NO:2所示之胺基酸序列、如SEQ ID NO:3所示之胺基酸序列、如SEQ ID NO:5所示之胺基酸序列、如SEQ ID NO:6所示之胺基酸序列、如SEQ ID NO:10所示之胺基酸序列、如SEQ ID NO:11所示之胺基酸序列、如SEQ ID NO:12所示之胺基酸序列、如SEQ ID NO:13所示之胺基酸序列、如SEQ ID NO:14所示之胺基酸序列、如SEQ ID NO:15所示之胺基酸序列、如SEQ ID NO:16所示之胺基酸序列及如SEQ ID NO:17所示之胺基酸序列所組成之群組。
在一具體實施例中,該至少一蛋白質進一步可包括選自由如SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:18、SEQ ID NO:19及SEQ ID NO:20所示之胺基酸序列所組成之群組。
在一具體實施例中,該病毒係來自選自由新型冠狀病毒(SARS-CoV-2)、中東呼吸道症候群冠狀病毒(middle east respiratory syndrome coronavirus, MERS-CoV)、嚴重急性呼吸道症候群冠狀病毒(SARS-CoV)、人類冠狀病毒HKU(HKU-CoV)、人類冠狀病毒229E(229E-CoV)、人類冠狀病毒NL63(NL63-CoV)、人類冠狀病毒OC43(OC43-CoV)、A型流感病毒H1N1亞型(influenza A virus subtype H1N1)、A型流感病毒H3N2亞型(influenza A virus subtype H3N2)及B型流感病毒(influenza B virus)所組成之群組。
在一具體實施例中,該待測樣本可來自一受試者之血液或血清。
在一具體實施例中,該第一抗體可為免疫球蛋白G(IgG)或免疫球蛋白A(IgA)。
在一具體實施例中,該生物製劑可為一單株抗體藥物或一受體阻斷劑。
在一具體實施例中,該單株抗體藥物可為一鼠源性單株抗體或一兔源性單株抗體。
在一具體實施例中,該單株抗體藥物可為抗新型冠狀病毒之棘蛋白的單株抗體、抗新型冠狀病毒之棘蛋白S1結構域的單株抗體或抗新型冠狀病毒之核鞘蛋白的單株抗體。
在一具體實施例中,該受體阻斷劑可為一人類細胞表面之血管收縮素轉化酶2(angiotensin-converting enzyme 2,ACE2)受體阻斷劑。
為了達成上述目的,本發明另提供一種病毒感染之檢測方法,可包括步驟:
提供如上所述之蛋白質微陣列;
將一非蛋白質之阻斷劑加入至該蛋白質微陣列之蛋白質陣列區塊上,反應5分鐘至10分鐘,以形成一第一蛋白質微陣列;
提供一受試者之血清,並將該血清加入至該第一蛋白質微陣列上,反應50分鐘至70分鐘後進行清洗,以形成一第二蛋白質微陣列;
提供一第二抗體且該第二抗體係經螢光標記或經酵素標記,將該第二抗體加入至該第二蛋白質微陣列上,反應25分鐘至35分鐘後進行清洗,以形成一第三蛋白質微陣列;以及
利用一訊號讀取機讀取自該第三蛋白質微陣列上所產生之光學訊號。
為了達成上述目的,本發明又提供一種如上所述之蛋白質微陣列之用途,其中該蛋白質微陣列係用於體外檢測一受試者是否受一病毒感染或用於評估一生物製劑對於阻斷該病毒感染之能力,且該病毒係選自由新型冠狀病毒、中東呼吸道症候群冠狀病毒、嚴重急性呼吸道症候群冠狀病毒、人類冠狀病毒HKU、人類冠狀病毒229E、人類冠狀病毒NL63、人類冠狀病毒OC43、A型流感病毒H1N1亞型、A型流感病毒H3N2亞型及B型流感病毒所組成之群組。
在一具體實施例中,該生物製劑可為一單株抗體藥物或一受體阻斷劑。為了達成上述目的,本發明再提供一種體外檢測病毒感染之試劑盒,可包括如上所述之蛋白質微陣列以及一第二抗體,其中該第二抗體配置用以與該第一抗體或該生物製劑產生專一性地結合。
在一具體實施例中,該第二抗體可為經螢光標記或經酵素標記。
在一具體實施例中,該螢光標記可包括花青染料(cyanine dye)Cy3及花青染料Cy5。
在一具體實施例中,其中該酵素標記可包括生物素(biotin)及毛地黃素(digoxigenin)。
本發明之蛋白質微陣列及體外檢測病毒感染之試劑盒可透過與受試者之血清進行反應,而達到快速地、靈敏地及準確地確定受試者是否受到病毒感染,且僅需花費約150分鐘即可完成檢測。此外,由於本發明之蛋白質微陣列及體外檢測病毒感染之試劑盒無須採集受試者之鼻咽腔黏膜之樣本,因此不會引起受試者之鼻腔或喉嚨不舒服感而導致受試者打噴嚏或咳嗽,進而降低病毒傳播之風險。另外,使用本發明之蛋白質微陣列及體外檢測病毒感染之試劑盒檢測受試者之血清中的IgG或IgA之靈敏度及專一性皆高達97%,因此,相較於現有技術之即時定量聚合酶連鎖反應之檢測方式,本發明之蛋白質微陣列及體外檢測病毒感染之試劑盒無須經多次採集樣本進行檢測,進而減少採集受試者之樣本次數及檢測次數。再者,使用本發明之蛋白質微陣列及體外檢測病毒感染之試劑盒可用於檢測受試者是否受到包括冠狀病毒及流感病毒之不同種類之病毒感染或用於評估諸如單株抗體藥物或受體阻斷劑之生物製劑對於阻斷病毒感染之能力,且該病毒之種類包括新型冠狀病毒、中東呼吸道症候群冠狀病毒、嚴重急性呼吸道症候群冠狀病毒、人類冠狀病毒HKU、人類冠狀病毒229E、人類冠狀病毒NL63、人類冠狀病毒OC43、A型流感病毒H1N1亞型、A型流感病毒H3N2亞型及B型流感病毒。
以下係藉由特定之具體實施例說明本發明之實施方式,熟習此技術之人士可藉由本說明書所揭示之內容瞭解本發明之其他優點與功效。然而,本發明中所揭示之例示性實施例僅出於說明之目的,不應被視為限制本發明之範圍。換言之,本發明亦可藉由其他不同的具體實施例加以施行或應用,本說明書中的各項細節亦可基於不同的觀點與應用,在不悖離本發明之精神下進行各種修飾與變更。
除非本文另有說明,否則說明書及所附申請專利範圍中所使用之單數形式「一」及「該」包括數個體。除非本文另有說明,否則說明書及所附申請專利範圍中所使用之術語「或」包括「及/或」之含義。
實施例1 製備蛋白質微陣列
下表1列出購自義翹神州生物技術有限公司(Sino Biological Inc.,中國大陸)之來自不同病毒之帶有組胺酸標籤(His-tag)的蛋白質,各蛋白質係作為檢測病毒感染之生物標誌物,且各蛋白質係分別來自新型冠狀病毒(SARS-CoV-2)、中東呼吸道症候群冠狀病毒(MERS-CoV)及嚴重急性呼吸道症候群冠狀病毒(SARS-CoV)之如胺基酸序列SEQ ID NO:1、SEQ ID NO:2及SEQ ID NO:3所示之棘蛋白(spike protein,以下簡稱S蛋白)、如胺基酸序列SEQ ID NO:4、SEQ ID NO:5及SEQ ID NO:6所示之核鞘蛋白(nucleocapsid protein,以下簡稱N蛋白)及如胺基酸序列SEQ ID NO:7、SEQ ID NO:8及SEQ ID NO:9所示之棘蛋白S1結構域(spike protein S1 domain,以下簡稱S蛋白S1結構域);分別來自人類冠狀病毒HKU(HKU-CoV)、人類冠狀病毒229E(229E-CoV)、人類冠狀病毒NL63(NL63-CoV)及人類冠狀病毒OC43(OC43-CoV)之如胺基酸序列SEQ ID NO:10、SEQ ID NO:11、 SEQ ID NO:12及SEQ ID NO:13所示之S蛋白,以及如胺基酸序列SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16及SEQ ID NO:17所示之N蛋白;以及分別來自A型流感病毒H1N1亞型(influenza A virus subtype H1N1)、A型流感病毒H3N2亞型(influenza A virus subtype H3N2)及B型流感病毒(influenza B virus)之如胺基酸序列SEQ ID NO:18、SEQ ID NO:19及SEQ ID NO:20所示之血球凝集素蛋白(hemagglutinin protein,以下簡稱HA蛋白)。
表1 來自不同病毒之帶有組胺酸標籤的蛋白質
蛋白質 | 病毒 | 胺基酸序列 | Uniprot蛋白質序列資料庫之編號 |
S蛋白 | SARS-CoV-2 | SEQ ID NO:1 | P0DTC2 (Val 16-Pro1213) |
MERS-CoV | SEQ ID NO:2 | K9N5Q8 (Met1-Trp1297) | |
SARS-CoV | SEQ ID NO:3 | P59594 (Met1-Pro1195) | |
N蛋白 | SARS-CoV-2 | SEQ ID NO:4 | P0DTC9 (Met1-Ala419) |
MERS-CoV | SEQ ID NO:5 | R9UM87 (Met1-Asp413) | |
SARS-CoV | SEQ ID NO:6 | P59595 (Met1-Ala422) | |
S蛋白S1結構域 | SARS-CoV-2 | SEQ ID NO:7 | P0DTC2 (Val 16-Arg685) |
MERS-CoV | SEQ ID NO:8 | K9N5Q8 (Met1-Glu725) | |
SARS-CoV | SEQ ID NO:9 | P59594 (Met1-Arg667) | |
S蛋白 | HKU-CoV | SEQ ID NO:10 | Q0ZME7 (Met1-Pro1295) |
229E-CoV | SEQ ID NO:11 | P15423 (Cys16-Trp1115) | |
NL63-CoV | SEQ ID NO:12 | Q6Q1S2 (Met1-Pro1296) | |
OC43-CoV | SEQ ID NO:13 | P36334 (Met1-Pro1304) | |
N蛋白 | HKU-CoV | SEQ ID NO:14 | Q5MQC6 (Met1-Ala441) |
229E-CoV | SEQ ID NO:15 | P15130 (Met1-Asn389) | |
NL63-CoV | SEQ ID NO:16 | Q6Q1R8 (Met1-His377) | |
OC43-CoV | SEQ ID NO:17 | P33469 (Met1-Ile448) | |
HA蛋白 | A型流感病毒H1N1亞型 | SEQ ID NO:18 | Q9WFX3 (Met 1-Gln 529) |
A型流感病毒H3N2亞型 | SEQ ID NO:19 | P03437 (Met 1-Trp 530) | |
B型流感病毒 | SEQ ID NO:20 | P03460 (Met 1-Ala 556) |
將玻璃載玻片依序以水、乙醇、丙酮及甲醇進行淋洗後,於65°C下,以20% KOH溶液清洗2小時,之後以體積比為3:1之H
2SO
4/H
2O
2溶液清洗12分鐘,以得到一經清洗之玻璃載玻片。之後,將該經清洗之玻璃載玻片進行塗布,該塗布包括步驟:以2.5% 3-胺基丙基三乙氧矽烷(3-aminopropyl triethoxysilane)(溶於酒精中)處理5分鐘後進行清洗並乾燥;以及,以pH 8.5, 0.5%戊二醛(溶於0.05 M硼酸鈉溶液中)處理16小時進行清洗並乾燥,之後得到 一經表面處理之玻璃載玻片,並將該經表面處理之玻璃載玻片於4°C下保存於真空密封袋內。
利用微陣列接觸式點樣系統(CapitalBio SmartArrayer™ 136, 中國大陸),將表1所示之各蛋白質及表2所示之11個控制組樣本,經三重覆點樣於經表面處理之玻璃載玻片上,以得到一蛋白質微陣列。將蛋白質微陣列於室溫下靜置隔夜後進行真空封裝,並保存於4℃或-80℃。
表2 控制組樣本
對照組及實驗組 | 化學物質 |
負對照組 | 牛血清蛋白 |
緩衝液 | |
正對照組 | Cy3-landmark |
Cy3 anti-human-IgG | |
Cy5-landmark | |
實驗組 | Poly-L-lysine |
Protein A | |
Human antibody | |
Anti-human-IgA | |
Anti-human-IgM | |
Anti-human-All |
實施例2 分析蛋白質微陣列之受體專一性及抗體專一性
本實施例利用位於人類細胞表面之血管收縮素轉化酶2(angiotensin-converting enzyme 2,ACE2)受體(義翹神州生物技術有限公司,中國大陸)檢測蛋白質微陣列之受體專一性,以及利用市售之抗SARS-CoV-2之S蛋白S1結構域的單株抗體(αS蛋白mAb)(購自義翹神州生物技術有限公司,中國大陸)及抗SARS-CoV-2之N蛋白的單株抗體(α N蛋白)(購自義翹神州生物技術有限公司,中國大陸)之抗體藥物檢測蛋白質微陣列之抗體專一性。
將經系列稀釋之25 ng、50 ng、75 ng、100 ng及125 ng之ACE2受體與蛋白質微陣列進行反應1小時,之後再以Cy3標記抗人IgG抗體與蛋白質微陣列進行反應30分鐘。參見第1A圖,結果顯示毫微克量級之ACE2能夠顯著地與蛋白質微陣列上之SARS-CoV-2 S蛋白及SARS-CoV S蛋白結合,且未與MERS-CoV S蛋白結合。
將經系列稀釋之100 pg、200 pg、300 pg及400 pg之αS蛋白mAb與蛋白質微陣列進行反應1小時,之後再以Cy5標記抗兔IgG抗體與蛋白質微陣列進行反應30分鐘。參見第1B圖,結果顯示微微克量級之αS蛋白mAb能夠顯著地與蛋白質微陣列上之SARS-CoV-2 S蛋白及SARS-CoV S蛋白結合,且未與MERS-CoV S蛋白結合。
將經系列稀釋之10 pg、20 pg、30 pg、40 pg及50 pg之αN蛋白mAb與蛋白質微陣列進行反應1小時,之後再以Cy5標記抗兔IgG抗體與蛋白質微陣列進行反應30分鐘。參見第1C圖,結果顯示微微克量級之αN蛋白mAb能夠顯著地與蛋白質微陣列上之SARS-CoV-2 N蛋白及SARS-CoV N蛋白結合,且未與MERS-CoV N蛋白結合。
上述結果顯見,蛋白質微陣列能夠有效地與ACE2受體以及與αS蛋白mAb及αN蛋白mAb專一性地結合,且αS蛋白mAb及αN蛋白mAb之最低檢測極限分別為200 pg及10 pg。因此,蛋白質微陣列能夠用以評估ACE2受體阻斷劑(block)藥物以及抗病毒之單株抗體藥物對於阻斷病毒感染之能力。
實施例3 分析蛋白質微陣列與血清中免疫球蛋白G(IgG)及免疫球蛋白A(IgA)之反應性
為了確認阻斷劑(blocking buffer)對於蛋白質微陣列之讀值準確度的影響,蛋白質微陣列以5%牛血清蛋白(bovine serum albumin, BSA)阻斷劑及HyBlock非蛋白質阻斷劑(購自翰新國際有限公司,台灣)分別阻斷非特異性抗原1小時及10分鐘後,與來自COVID-19患者之0.1 μl血清反應1小時;之後蛋白質微陣列以TBST緩衝液清洗,並與Cy3標記抗人IgG抗體或Cy5標記抗人IgA抗體進行雜合反應30分鐘;最後,蛋白質微陣列以TBST緩衝液清洗後,利用螢光檢測系統(機型:“瀚生”微陣列晶片掃描儀,瀚生醫電股份有限公司,台灣)檢測蛋白質微陣列之背景螢光。參見第2A圖及第2B圖,結果顯示相較於5% BSA阻斷劑,使用HyBlock非蛋白質阻斷劑蛋白質微陣列上之非特異性抗原,可縮短蛋白質微陣列之檢測時間為150分鐘且可得到背景螢光更為乾淨之的Cy3或Cy5螢光檢測結果。
蛋白質微陣列以HyBlock非蛋白質阻斷劑阻斷非特異性抗原10分鐘後,分別與來自32位COVID-19患者及32位檢康受試者之0.1 μl血清反應1小時;之後各蛋白質微陣列以TBST緩衝液清洗,並與Cy3標記抗人IgG抗體或Cy5標記抗人IgA抗體進行雜合反應30分鐘;最後,蛋白質微陣列以TBST緩衝液清洗後,利用螢光檢測系統檢測蛋白質微陣列之Cy3螢光或Cy5螢光。
參見第3A圖及第3B圖,結果顯示蛋白質微陣列能夠顯著地區分來自COVID-19患者及來自檢康受試者之血清中IgG與SARS-CoV-2 S蛋白及SARS-CoV-2 N蛋白之反應性。第3C圖及第3D圖,結果顯示蛋白質微陣列能夠顯著地區分來自COVID-19患者及來自檢康受試者之血清中IgG與SARS-CoV S蛋白及SARS-CoV N蛋白之反應性。
參見第3E圖及第3F圖,結果顯示蛋白質微陣列能夠顯著地區分來自COVID-19患者及來自檢康受試者之血清中IgA與SARS-CoV-2 S蛋白及SARS-CoV-2 N蛋白之反應性。第3G圖及第3H圖,結果顯示蛋白質微陣列能夠顯著地區分來自COVID-19患者及來自檢康受試者之血清中IgA與SARS-CoV S蛋白及SARS-CoV N蛋白之反應性。
上述結果證實,蛋白質微陣列可有效地區分來自COVID-19患者及來自檢康受試者之血清中IgG及IgA之反應性,並用以檢測受試者之血清,以判斷受試者是否罹患COVID-19。
實施例4 評估具有單一生物標誌物或兩種生物標誌物之組合之蛋白質微陣列對於檢測來自COVID-19患者之血清中IgG或IgA之專一性及靈敏度
如表4所示,將具有不同的單一生物標誌物或兩種生物標誌物之組合之蛋白質微陣列以HyBlock非蛋白質阻斷劑阻斷非特異性抗原10分鐘後,分別與來自36位COVID-19患者之0.1 μl血清反應1小時;之後各蛋白質微陣列以TBST緩衝液清洗,並與Cy3標記抗人IgG抗體或Cy5標記抗人IgA抗體進行雜合反應30分鐘;最後,蛋白質微陣列以TBST緩衝液清洗後,利用螢光檢測系統檢測蛋白質微陣列之Cy3螢光或Cy5螢光。
參見表4,結果顯示具有SARS-CoV-2 S蛋白之單一生物標誌物的蛋白質微陣列用於檢測COVID-19患者之血清IgG的靈敏度及專一性分別為90.6%及97.2%,且用於檢測COVID-19患者之血清IgA的靈敏度及專一性分別為84.4%及100%。此外, 組合SARS-CoV-2 S蛋白及SARS-CoV-2 N蛋白之蛋白質微陣列用於檢測COVID-19患者之血清IgG的靈敏度及專一性皆高達97%。
表4 具有不同的單一生物標誌物或生物標誌物之組合之蛋白質微陣列對於檢測來自COVID-19患者之血清中IgG或IgA之專一性及靈敏度
生物標誌物及血清 | 靈敏度(%) | 專一性(%) |
SARS-CoV-2 S蛋白 IgG | 90.6 | 97.2 |
SARS-CoV-2 S蛋白 IgA | 84.4 | 100 |
SARS-CoV-2 N蛋白 IgG | 65.6 | 100 |
SARS-CoV N蛋白 IgG | 65.6 | 100 |
SARS-CoV S蛋白 IgG | 65.6 | 97.2 |
SARS-CoV-2 S蛋白 IgG + SARS-CoV-2 N蛋白 IgG | 96.9 | 97.2 |
SARS-CoV-2 S蛋白 IgG + SARS-CoV-2 S蛋白 IgA | 93.8 | 97.2 |
SARS-CoV-2 S蛋白 IgG + SARS-CoV N蛋白 IgG | 93.8 | 97.2 |
SARS-CoV-2 S蛋白 IgG + SARS-CoV S蛋白 IgG | 90.6 | 97.2 |
實施例5 分析蛋白質微陣列上之SARS-CoV-2 S蛋白及SARS-CoV-2 N蛋白與不同種類之病毒之間的交叉反應性
利用蛋白質微陣列分別檢測來自COVID-19患者之血清中IgG與SARS-CoV-2 S蛋白、SARS-CoV-2 S蛋白S1結構域、SARS-CoV S蛋白、HKU-CoV S蛋白、OC43-CoV S蛋白、A型流感病毒H3N2亞型HA蛋白、SARS-CoV-2 N蛋白及SARS-CoV N蛋白之反應性,並分別分析SARS-CoV-2 S蛋白與SARS-CoV-2 S蛋白S1結構域、SARS-CoV S蛋白、HKU-CoV S蛋白、OC43-CoV S蛋白及A型流感病毒H3N2亞型HA蛋白之間的交叉反應性,以及SARS-CoV-2 N蛋白及SARS-CoV N蛋白之間的交叉反應性。
參見第4A至第4E圖,結果顯示COVID-19患者之血清中IgG抗SARS-CoV-2 S蛋白與SARS-CoV-2 S蛋白S1結構域、SARS-CoV S蛋白、HKU-CoV S蛋白、OC43-CoV S蛋白及A型流感病毒H3N2亞型HA蛋白之間具有交叉反應性。第4F圖結果顯示COVID-19患者之血清中IgG抗SARS-CoV-2 N蛋白與SARS-CoV N蛋白之間具有交叉反應性。
此外,利用蛋白質微陣列分別檢測來自COVID-19患者之血清中IgA與SARS-CoV-2 S蛋白、SARS-CoV-2 S蛋白S1結構域、SARS-CoV S蛋白、HKU-CoV S蛋白、OC43-CoV S蛋白、SARS-CoV-2 N蛋白、SARS-CoV N蛋白及229E-CoV-S蛋白之反應性,並分別分析SARS-CoV-2 S蛋白與SARS-CoV-2 S蛋白S1結構域、SARS-CoV S蛋白、HKU-CoV S蛋白及OC43-CoV S蛋白之間的交叉反應性,以及SARS-CoV-2 N蛋白與SARS-CoV N蛋白及及229E-CoV-S蛋白之間的交叉反應性。
參見第5A至第5D圖,結果顯示COVID-19患者之血清中IgA抗SARS-CoV-2 S蛋白與SARS-CoV-2 S蛋白S1結構域、SARS-CoV S蛋白、HKU-CoV S蛋白及OC43-CoV S蛋白之間具有交叉反應性。此外,第5E圖及第5F圖結果顯示COVID-19患者之血清中IgA抗SARS-CoV-2 N蛋白與SARS-CoV N蛋白及229E-CoV-S蛋白之間具有交叉反應性。
基於上述結果,透過來自COVID-19患者之血清中IgG或IgA進行檢測,顯示SARS-CoV-2 S蛋白與SARS-CoV-2 S蛋白S1結構域、SARS-CoV S蛋白、HKU-CoV S蛋白、OC43-CoV S蛋白及A型流感病毒H3N2亞型HA蛋白之間具有正相關之交叉反應性,且SARS-CoV-2 N蛋白與SARS-CoV N蛋白及229E-CoV-S蛋白之間具有交叉反應性。證實蛋白質微陣列之SARS-CoV-2 S蛋白SARS-CoV-2 N蛋白能夠用於檢測不同種類之冠狀病毒及流感病毒。
雖然本發明已以較佳實施例揭露,然其並非用以限制本發明,任何熟習此項技藝之人士,在不脫離本發明之精神和範圍內,當可作各種更動與修飾,因此本發明之保護範圍當視後附之申請專利範圍所界定者為準。
第1A圖係本發明之蛋白質微陣列與人類細胞表面之血管收縮素轉化酶2(angiotensin-converting enzyme 2,ACE2)之受體專一性的結果圖。結果由t-檢定(t-test)分析,* p < 0.05且*** p < 0.001(相較於MERS-CoV)。
第1B圖係本發明之蛋白質微陣列與抗SARS-COV-2之棘蛋白(S蛋白)S1結構域的單株抗體之受體專一性的結果圖。結果由t-檢定(t-test)分析,* p < 0.05且*** p < 0.001 (相較於MERS-CoV)。
第1C圖係本發明之蛋白質微陣列與抗SARS-COV-2之核鞘蛋白(N蛋白)的單株抗體之受體專一性的結果圖。結果由t-檢定(t-test)分析,* p < 0.05且*** p < 0.001 (相較於MERS-CoV)。
第2A圖係本發明之蛋白質微陣列分別經5%牛血清蛋白(bovine serum albumin, BSA)阻斷劑及HyBlock非蛋白質阻斷劑進行非特異性抗原之阻斷,並檢測背景之Cy3螢光強度。結果由t-檢定(t-test)分析,* p < 0.05且*** p < 0.001(相較於以BSA處理1小時)。
第2B圖係本發明之蛋白質微陣列分別經5%牛血清蛋白(bovine serum albumin, BSA)阻斷劑及HyBlock非蛋白質阻斷劑進行非特異性抗原之阻斷,並檢測背景之Cy5螢光強度。結果由t-檢定(t-test)分析,* p < 0.05且*** p < 0.001(相較於以BSA處理1小時)。
第3A圖係利用本發明之蛋白質微陣列檢測來自COVID-19患者及來自檢康受試者之血清中IgG與SARS-CoV-2 S蛋白之反應性的結果圖。
第3B圖係利用本發明之蛋白質微陣列檢測來自COVID-19患者及來自檢康受試者之血清中IgG與SARS-CoV-2 N蛋白之反應性的結果圖。
第3C圖係利用本發明之蛋白質微陣列檢測來自COVID-19患者及來自檢康受試者之血清中IgG與SARS-CoV S蛋白之反應性的結果圖。
第3D圖係利用本發明之蛋白質微陣列檢測來自COVID-19患者及來自檢康受試者之血清中IgG與SARS-CoV N蛋白之反應性的結果圖。
第3E圖係利用本發明之蛋白質微陣列檢測來自COVID-19患者及來自檢康受試者之血清中IgA與SARS-CoV-2 S蛋白之反應性的結果圖。
第3F圖係利用本發明之蛋白質微陣列檢測來自COVID-19患者及來自檢康受試者之血清中IgA與SARS-CoV-2 N蛋白之反應性的結果圖。
第3G圖係利用本發明之蛋白質微陣列檢測來自COVID-19患者及來自檢康受試者之血清中IgA與SARS-CoV S蛋白之反應性的結果圖。
第3H圖係利用本發明之蛋白質微陣列檢測來自COVID-19患者及來自檢康受試者之血清中IgA與SARS-CoV N蛋白之反應性的結果圖。
第4A圖係分析本發明之蛋白質微陣列檢測來自COVID-19患者之血清中IgG分別與SARS-CoV-2 S蛋白及SARS-CoV-2 S蛋白S1結構域之交叉反應性的結果圖。
第4B圖係分析本發明之蛋白質微陣列檢測來自COVID-19患者之血清中IgG分別與SARS-CoV-2 S蛋白及SARS-CoV S蛋白之交叉反應性的結果圖。
第4C圖係分析本發明之蛋白質微陣列檢測來自COVID-19患者之血清中IgG分別與SARS-CoV-2 S蛋白及HKU-CoV S蛋白之交叉反應性的結果圖。
第4D圖係分析本發明之蛋白質微陣列檢測來自COVID-19患者之血清中IgG分別與SARS-CoV-2 S蛋白及OC43-CoV S蛋白之交叉反應性的結果圖。
第4E圖係分析本發明之蛋白質微陣列檢測來自COVID-19患者之血清中IgG分別與SARS-CoV-2 S蛋白及A型流感病毒H3N2亞型HA蛋白之交叉反應性的結果圖。
第4F圖係分析本發明之蛋白質微陣列檢測來自COVID-19患者之血清中IgG分別與SARS-CoV-2 N蛋白及SARS-CoV N蛋白之交叉反應性的結果圖。
第5A圖係分析本發明之蛋白質微陣列檢測來自COVID-19患者之血清中IgA分別與SARS-CoV-2 S蛋白及SARS-CoV-2 S蛋白S1結構域之交叉反應性的結果圖。
第5B圖係分析本發明之蛋白質微陣列檢測來自COVID-19患者之血清中IgA分別與SARS-CoV-2 S蛋白及SARS-CoV S蛋白之交叉反應性的結果圖。
第5C圖係分析本發明之蛋白質微陣列檢測來自COVID-19患者之血清中IgA分別與SARS-CoV-2 S蛋白及HKU-CoV S蛋白之交叉反應性的結果圖。
第5D圖係分析本發明之蛋白質微陣列檢測來自COVID-19患者之血清中IgA分別與SARS-CoV-2 S蛋白及OC43-CoV S蛋白之交叉反應性的結果圖。
第5E圖係分析本發明之蛋白質微陣列檢測來自COVID-19患者之血清中IgA分別與SARS-CoV-2 N蛋白及SARS-CoV N蛋白之交叉反應性的結果圖。
第5F圖係分析本發明之蛋白質微陣列檢測來自COVID-19患者之血清中IgA分別與SARS-CoV-2 N蛋白及229E-CoV-S蛋白之交叉反應性的結果圖。
序列表 <![CDATA[<110> 國立成功大學]]> <![CDATA[<120> 蛋白質微陣列、其檢測方法、其用途及含有該蛋白質微陣列之試劑盒]]> <![CDATA[<130> TP203656-TW]]> <![CDATA[<160> 20 ]]> <![CDATA[<170> PatentIn version 3.5]]> <![CDATA[<210> 1]]> <![CDATA[<211> 1281]]> <![CDATA[<212> PRT]]> <![CDATA[<213> SARS-CoV-2 病毒]]> <![CDATA[<400> 1]]> 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 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 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 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 Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 290 295 300 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 305 310 315 320 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 325 330 335 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 340 345 350 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 355 360 365 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 370 375 380 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 385 390 395 400 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 405 410 415 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 420 425 430 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 435 440 445 Gly Gly Asn Tyr Asn Tyr Leu Tyr Leu Tyr Arg Leu Phe Arg Lys Ser 450 455 460 Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala 465 470 475 480 Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro 485 490 495 Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro 500 505 510 Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr 515 520 525 Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val 530 535 540 Asn Phe Asn Phe Asn Gly Leu Thr Leu Thr Gly Thr Gly Val Leu Thr 545 550 555 560 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 565 570 575 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 580 585 590 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 595 600 605 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 610 615 620 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 625 630 635 640 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 645 650 655 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 660 665 670 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 675 680 685 Arg Arg Ala Arg Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 690 695 700 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 705 710 715 720 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 725 730 735 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 740 745 750 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 755 760 765 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 770 775 780 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 785 790 795 800 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 805 810 815 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 820 825 830 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 835 840 845 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 850 855 860 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 865 870 875 880 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 885 890 895 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 900 905 910 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 915 920 925 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 930 935 940 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 945 950 955 960 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 965 970 975 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 980 985 990 Lys Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 995 1000 1005 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala 1010 1015 1020 Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu 1025 1030 1035 Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly 1040 1045 1050 Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val 1055 1060 1065 Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr 1070 1075 1080 Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg 1085 1090 1095 Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln 1100 1105 1110 Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe 1115 1120 1125 Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr 1130 1135 1140 Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu 1145 1150 1155 Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu 1160 1165 1170 Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys 1175 1180 1185 Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser 1190 1195 1200 Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 1205 1210 1215 Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala 1220 1225 1230 Ile Val Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys 1235 1240 1245 Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe 1250 1255 1260 Asp Glu Asp Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu 1265 1270 1275 His Tyr Thr 1280 <![CDATA[<210> 2]]> <![CDATA[<211> 1353]]> <![CDATA[<212> PRT]]> <![CDATA[<213> MERS-CoV 病毒]]> <![CDATA[<400> 2]]> Met Ile His Ser Val Phe Leu Leu Met Phe Leu Leu Thr Pro Thr Glu 1 5 10 15 Ser Tyr Val Asp Val Gly Pro Asp Ser Val Lys Ser Ala Cys Ile Glu 20 25 30 Val Asp Ile Gln Gln Thr Phe Phe Asp Lys Thr Trp Pro Arg Pro Ile 35 40 45 Asp Val Ser Lys Ala Asp Gly Ile Ile Tyr Pro Gln Gly Arg Thr Tyr 50 55 60 Ser Asn Ile Thr Ile Thr Tyr Gln Gly Leu Phe Pro Tyr Gln Gly Asp 65 70 75 80 His Gly Asp Met Tyr Val Tyr Ser Ala Gly His Ala Thr Gly Thr Thr 85 90 95 Pro Gln Lys Leu Phe Val Ala Asn Tyr Ser Gln Asp Val Lys Gln Phe 100 105 110 Ala Asn Gly Phe Val Val Arg Ile Gly Ala Ala Ala Asn Ser Thr Gly 115 120 125 Thr Val Ile Ile Ser Pro Ser Thr Ser Ala Thr Ile Arg Lys Ile Tyr 130 135 140 Pro Ala Phe Met Leu Gly Ser Ser Val Gly Asn Phe Ser Asp Gly Lys 145 150 155 160 Met Gly Arg Phe Phe Asn His Thr Leu Val Leu Leu Pro Asp Gly Cys 165 170 175 Gly Thr Leu Leu Arg Ala Phe Tyr Cys Ile Leu Glu Pro Arg Ser Gly 180 185 190 Asn His Cys Pro Ala Gly Asn Ser Tyr Thr Ser Phe Ala Thr Tyr His 195 200 205 Thr Pro Ala Thr Asp Cys Ser Asp Gly Asn Tyr Asn Arg Asn Ala Ser 210 215 220 Leu Asn Ser Phe Lys Glu Tyr Phe Asn Leu Arg Asn Cys Thr Phe Met 225 230 235 240 Tyr Thr Tyr Asn Ile Thr Glu Asp Glu Ile Leu Glu Trp Phe Gly Ile 245 250 255 Thr Gln Thr Ala Gln Gly Val His Leu Phe Ser Ser Arg Tyr Val Asp 260 265 270 Leu Tyr Gly Gly Asn Met Phe Gln Phe Ala Thr Leu Pro Val Tyr Asp 275 280 285 Thr Ile Lys Tyr Tyr Ser Ile Ile Pro His Ser Ile Arg Ser Ile Gln 290 295 300 Ser Asp Arg Lys Ala Trp Ala Ala Phe Tyr Val Tyr Lys Leu Gln Pro 305 310 315 320 Leu Thr Phe Leu Leu Asp Phe Ser Val Asp Gly Tyr Ile Arg Arg Ala 325 330 335 Ile Asp Cys Gly Phe Asn Asp Leu Ser Gln Leu His Cys Ser Tyr Glu 340 345 350 Ser Phe Asp Val Glu Ser Gly Val Tyr Ser Val Ser Ser Phe Glu Ala 355 360 365 Lys Pro Ser Gly Ser Val Val Glu Gln Ala Glu Gly Val Glu Cys Asp 370 375 380 Phe Ser Pro Leu Leu Ser Gly Thr Pro Pro Gln Val Tyr Asn Phe Lys 385 390 395 400 Arg Leu Val Phe Thr Asn Cys Asn Tyr Asn Leu Thr Lys Leu Leu Ser 405 410 415 Leu Phe Ser Val Asn Asp Phe Thr Cys Ser Gln Ile Ser Pro Ala Ala 420 425 430 Ile Ala Ser Asn Cys Tyr Ser Ser Leu Ile Leu Asp Tyr Phe Ser Tyr 435 440 445 Pro Leu Ser Met Lys Ser Asp Leu Ser Val Ser Ser Ala Gly Pro Ile 450 455 460 Ser Gln Phe Asn Tyr Lys Gln Ser Phe Ser Asn Pro Thr Cys Leu Ile 465 470 475 480 Leu Ala Thr Val Pro His Asn Leu Thr Thr Ile Thr Lys Pro Leu Lys 485 490 495 Tyr Ser Tyr Ile Asn Lys Cys Ser Arg Leu Leu Ser Asp Asp Arg Thr 500 505 510 Glu Val Pro Gln Leu Val Asn Ala Asn Gln Tyr Ser Pro Cys Val Ser 515 520 525 Ile Val Pro Ser Thr Val Trp Glu Asp Gly Asp Tyr Tyr Arg Lys Gln 530 535 540 Leu Ser Pro Leu Glu Gly Gly Gly Trp Leu Val Ala Ser Gly Ser Thr 545 550 555 560 Val Ala Met Thr Glu Gln Leu Gln Met Gly Phe Gly Ile Thr Val Gln 565 570 575 Tyr Gly Thr Asp Thr Asn Ser Val Cys Pro Lys Leu Glu Phe Ala Asn 580 585 590 Asp Thr Lys Ile Ala Ser Gln Leu Gly Asn Cys Val Glu Tyr Ser Leu 595 600 605 Tyr Gly Val Ser Gly Arg Gly Val Phe Gln Asn Cys Thr Ala Val Gly 610 615 620 Val Arg Gln Gln Arg Phe Val Tyr Asp Ala Tyr Gln Asn Leu Val Gly 625 630 635 640 Tyr Tyr Ser Asp Asp Gly Asn Tyr Tyr Cys Leu Arg Ala Cys Val Ser 645 650 655 Val Pro Val Ser Val Ile Tyr Asp Lys Glu Thr Lys Thr His Ala Thr 660 665 670 Leu Phe Gly Ser Val Ala Cys Glu His Ile Ser Ser Thr Met Ser Gln 675 680 685 Tyr Ser Arg Ser Thr Arg Ser Met Leu Lys Arg Arg Asp Ser Thr Tyr 690 695 700 Gly Pro Leu Gln Thr Pro Val Gly Cys Val Leu Gly Leu Val Asn Ser 705 710 715 720 Ser Leu Phe Val Glu Asp Cys Lys Leu Pro Leu Gly Gln Ser Leu Cys 725 730 735 Ala Leu Pro Asp Thr Pro Ser Thr Leu Thr Pro Arg Ser Val Arg Ser 740 745 750 Val Pro Gly Glu Met Arg Leu Ala Ser Ile Ala Phe Asn His Pro Ile 755 760 765 Gln Val Asp Gln Leu Asn Ser Ser Tyr Phe Lys Leu Ser Ile Pro Thr 770 775 780 Asn Phe Ser Phe Gly Val Thr Gln Glu Tyr Ile Gln Thr Thr Ile Gln 785 790 795 800 Lys Val Thr Val Asp Cys Lys Gln Tyr Val Cys Asn Gly Phe Gln Lys 805 810 815 Cys Glu Gln Leu Leu Arg Glu Tyr Gly Gln Phe Cys Ser Lys Ile Asn 820 825 830 Gln Ala Leu His Gly Ala Asn Leu Arg Gln Asp Asp Ser Val Arg Asn 835 840 845 Leu Phe Ala Ser Val Lys Ser Ser Gln Ser Ser Pro Ile Ile Pro Gly 850 855 860 Phe Gly Gly Asp Phe Asn Leu Thr Leu Leu Glu Pro Val Ser Ile Ser 865 870 875 880 Thr Gly Ser Arg Ser Ala Arg Ser Ala Ile Glu Asp Leu Leu Phe Asp 885 890 895 Lys Val Thr Ile Ala Asp Pro Gly Tyr Met Gln Gly Tyr Asp Asp Cys 900 905 910 Met Gln Gln Gly Pro Ala Ser Ala Arg Asp Leu Ile Cys Ala Gln Tyr 915 920 925 Val Ala Gly Tyr Lys Val Leu Pro Pro Leu Met Asp Val Asn Met Glu 930 935 940 Ala Ala Tyr Thr Ser Ser Leu Leu Gly Ser Ile Ala Gly Val Gly Trp 945 950 955 960 Thr Ala Gly Leu Ser Ser Phe Ala Ala Ile Pro Phe Ala Gln Ser Ile 965 970 975 Phe Tyr Arg Leu Asn Gly Val Gly Ile Thr Gln Gln Val Leu Ser Glu 980 985 990 Asn Gln Lys Leu Ile Ala Asn Lys Phe Asn Gln Ala Leu Gly Ala Met 995 1000 1005 Gln Thr Gly Phe Thr Thr Thr Asn Glu Ala Phe Gln Lys Val Gln 1010 1015 1020 Asp Ala Val Asn Asn Asn Ala Gln Ala Leu Ser Lys Leu Ala Ser 1025 1030 1035 Glu Leu Ser Asn Thr Phe Gly Ala Ile Ser Ala Ser Ile Gly Asp 1040 1045 1050 Ile Ile Gln Arg Leu Asp Val Leu Glu Gln Asp Ala Gln Ile Asp 1055 1060 1065 Arg Leu Ile Asn Gly Arg Leu Thr Thr Leu Asn Ala Phe Val Ala 1070 1075 1080 Gln Gln Leu Val Arg Ser Glu Ser Ala Ala Leu Ser Ala Gln Leu 1085 1090 1095 Ala Lys Asp Lys Val Asn Glu Cys Val Lys Ala Gln Ser Lys Arg 1100 1105 1110 Ser Gly Phe Cys Gly Gln Gly Thr His Ile Val Ser Phe Val Val 1115 1120 1125 Asn Ala Pro Asn Gly Leu Tyr Phe Met His Val Gly Tyr Tyr Pro 1130 1135 1140 Ser Asn His Ile Glu Val Val Ser Ala Tyr Gly Leu Cys Asp Ala 1145 1150 1155 Ala Asn Pro Thr Asn Cys Ile Ala Pro Val Asn Gly Tyr Phe Ile 1160 1165 1170 Lys Thr Asn Asn Thr Arg Ile Val Asp Glu Trp Ser Tyr Thr Gly 1175 1180 1185 Ser Ser Phe Tyr Ala Pro Glu Pro Ile Thr Ser Leu Asn Thr Lys 1190 1195 1200 Tyr Val Ala Pro Gln Val Thr Tyr Gln Asn Ile Ser Thr Asn Leu 1205 1210 1215 Pro Pro Pro Leu Leu Gly Asn Ser Thr Gly Ile Asp Phe Gln Asp 1220 1225 1230 Glu Leu Asp Glu Phe Phe Lys Asn Val Ser Thr Ser Ile Pro Asn 1235 1240 1245 Phe Gly Ser Leu Thr Gln Ile Asn Thr Thr Leu Leu Asp Leu Thr 1250 1255 1260 Tyr Glu Met Leu Ser Leu Gln Gln Val Val Lys Ala Leu Asn Glu 1265 1270 1275 Ser Tyr Ile Asp Leu Lys Glu Leu Gly Asn Tyr Thr Tyr Tyr Asn 1280 1285 1290 Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Val 1295 1300 1305 Ala Leu Ala Leu Cys Val Phe Phe Ile Leu Cys Cys Thr Gly Cys 1310 1315 1320 Gly Thr Asn Cys Met Gly Lys Leu Lys Cys Asn Arg Cys Cys Asp 1325 1330 1335 Arg Tyr Glu Glu Tyr Asp Leu Glu Pro His Lys Val His Val His 1340 1345 1350 <![CDATA[<210> 3]]> <![CDATA[<211> 422]]> <![CDATA[<212> PRT]]> <![CDATA[<213> SARS-CoV 病毒]]> <![CDATA[<400> 3]]> Met Ser Asp Asn Gly Pro Gln Ser Asn Gln Arg Ser Ala Pro Arg Ile 1 5 10 15 Thr Phe Gly Gly Pro Thr Asp Ser Thr Asp Asn Asn Gln Asn Gly Gly 20 25 30 Arg Asn Gly Ala Arg Pro Lys Gln Arg Arg Pro Gln Gly Leu Pro Asn 35 40 45 Asn Thr Ala Ser Trp Phe Thr Ala Leu Thr Gln His Gly Lys Glu Glu 50 55 60 Leu Arg Phe Pro Arg Gly Gln Gly Val Pro Ile Asn Thr Asn Ser Gly 65 70 75 80 Pro Asp Asp Gln Ile Gly Tyr Tyr Arg Arg Ala Thr Arg Arg Val Arg 85 90 95 Gly Gly Asp Gly Lys Met Lys Glu Leu Ser Pro Arg Trp Tyr Phe Tyr 100 105 110 Tyr Leu Gly Thr Gly Pro Glu Ala Ser Leu Pro Tyr Gly Ala Asn Lys 115 120 125 Glu Gly Ile Val Trp Val Ala Thr Glu Gly Ala Leu Asn Thr Pro Lys 130 135 140 Asp His Ile Gly Thr Arg Asn Pro Asn Asn Asn Ala Ala Thr Val Leu 145 150 155 160 Gln Leu Pro Gln Gly Thr Thr Leu Pro Lys Gly Phe Tyr Ala Glu Gly 165 170 175 Ser Arg Gly Gly Ser Gln Ala Ser Ser Arg Ser Ser Ser Arg Ser Arg 180 185 190 Gly Asn Ser Arg Asn Ser Thr Pro Gly Ser Ser Arg Gly Asn Ser Pro 195 200 205 Ala Arg Met Ala Ser Gly Gly Gly Glu Thr Ala Leu Ala Leu Leu Leu 210 215 220 Leu Asp Arg Leu Asn Gln Leu Glu Ser Lys Val Ser Gly Lys Gly Gln 225 230 235 240 Gln Gln Gln Gly Gln Thr Val Thr Lys Lys Ser Ala Ala Glu Ala Ser 245 250 255 Lys Lys Pro Arg Gln Lys Arg Thr Ala Thr Lys Gln Tyr Asn Val Thr 260 265 270 Gln Ala Phe Gly Arg Arg Gly Pro Glu Gln Thr Gln Gly Asn Phe Gly 275 280 285 Asp Gln Asp Leu Ile Arg Gln Gly Thr Asp Tyr Lys His Trp Pro Gln 290 295 300 Ile Ala Gln Phe Ala Pro Ser Ala Ser Ala Phe Phe Gly Met Ser Arg 305 310 315 320 Ile Gly Met Glu Val Thr Pro Ser Gly Thr Trp Leu Thr Tyr His Gly 325 330 335 Ala Ile Lys Leu Asp Asp Lys Asp Pro Gln Phe Lys Asp Asn Val Ile 340 345 350 Leu Leu Asn Lys His Ile Asp Ala Tyr Lys Thr Phe Pro Pro Thr Glu 355 360 365 Pro Lys Lys Asp Lys Lys Lys Lys Thr Asp Glu Ala Gln Pro Leu Pro 370 375 380 Gln Arg Gln Lys Lys Gln Pro Thr Val Thr Leu Leu Pro Ala Ala Asp 385 390 395 400 Met Asp Asp Phe Ser Arg Gln Leu Gln Asn Ser Met Ser Gly Ala Ser 405 410 415 Ala Asp Ser Thr Gln Ala 420 <![CDATA[<210> 4]]> <![CDATA[<211> 419]]> <![CDATA[<212> PRT]]> <![CDATA[<213> SARS-CoV-2 病毒]]> <![CDATA[<400> 4]]> Met Ser Asp Asn Gly Pro Gln Asn Gln Arg Asn Ala Pro Arg Ile Thr 1 5 10 15 Phe Gly Gly Pro Ser Asp Ser Thr Gly Ser Asn Gln Asn Gly Glu Arg 20 25 30 Ser Gly Ala Arg Ser Lys Gln Arg Arg Pro Gln Gly Leu Pro Asn Asn 35 40 45 Thr Ala Ser Trp Phe Thr Ala Leu Thr Gln His Gly Lys Glu Asp Leu 50 55 60 Lys Phe Pro Arg Gly Gln Gly Val Pro Ile Asn Thr Asn Ser Ser Pro 65 70 75 80 Asp Asp Gln Ile Gly Tyr Tyr Arg Arg Ala Thr Arg Arg Ile Arg Gly 85 90 95 Gly Asp Gly Lys Met Lys Asp Leu Ser Pro Arg Trp Tyr Phe Tyr Tyr 100 105 110 Leu Gly Thr Gly Pro Glu Ala Gly Leu Pro Tyr Gly Ala Asn Lys Asp 115 120 125 Gly Ile Ile Trp Val Ala Thr Glu Gly Ala Leu Asn Thr Pro Lys Asp 130 135 140 His Ile Gly Thr Arg Asn Pro Ala Asn Asn Ala Ala Ile Val Leu Gln 145 150 155 160 Leu Pro Gln Gly Thr Thr Leu Pro Lys Gly Phe Tyr Ala Glu Gly Ser 165 170 175 Arg Gly Gly Ser Gln Ala Ser Ser Arg Ser Ser Ser Arg Ser Arg Asn 180 185 190 Ser Ser Arg Asn Ser Thr Pro Gly Ser Ser Arg Gly Thr Ser Pro Ala 195 200 205 Arg Met Ala Gly Asn Gly Gly Asp Ala Ala Leu Ala Leu Leu Leu Leu 210 215 220 Asp Arg Leu Asn Gln Leu Glu Ser Lys Met Ser Gly Lys Gly Gln Gln 225 230 235 240 Gln Gln Gly Gln Thr Val Thr Lys Lys Ser Ala Ala Glu Ala Ser Lys 245 250 255 Lys Pro Arg Gln Lys Arg Thr Ala Thr Lys Ala Tyr Asn Val Thr Gln 260 265 270 Ala Phe Gly Arg Arg Gly Pro Glu Gln Thr Gln Gly Asn Phe Gly Asp 275 280 285 Gln Glu Leu Ile Arg Gln Gly Thr Asp Tyr Lys His Trp Pro Gln Ile 290 295 300 Ala Gln Phe Ala Pro Ser Ala Ser Ala Phe Phe Gly Met Ser Arg Ile 305 310 315 320 Gly Met Glu Val Thr Pro Ser Gly Thr Trp Leu Thr Tyr Thr Gly Ala 325 330 335 Ile Lys Leu Asp Asp Lys Asp Pro Asn Phe Lys Asp Gln Val Ile Leu 340 345 350 Leu Asn Lys His Ile Asp Ala Tyr Lys Thr Phe Pro Pro Thr Glu Pro 355 360 365 Lys Lys Asp Lys Lys Lys Lys Ala Asp Glu Thr Gln Ala Leu Pro Gln 370 375 380 Arg Gln Lys Lys Gln Gln Thr Val Thr Leu Leu Pro Ala Ala Asp Leu 385 390 395 400 Asp Asp Phe Ser Lys Gln Leu Gln Gln Ser Met Ser Ser Ala Asp Ser 405 410 415 Thr Gln Ala <![CDATA[<210> 5]]> <![CDATA[<211> 413]]> <![CDATA[<212> PRT]]> <![CDATA[<213> MERS-CoV 病毒]]> <![CDATA[<400> 5]]> Met Ala Ser Pro Ala Ala Pro Arg Ala Val Ser Phe Ala Asp Asn Asn 1 5 10 15 Asp Ile Thr Asn Thr Asn Leu Ser Arg Gly Arg Gly Arg Asn Pro Lys 20 25 30 Pro Arg Ala Ala Pro Asn Asn Thr Val Ser Trp Tyr Thr Gly Leu Thr 35 40 45 Gln His Gly Lys Val Pro Leu Thr Phe Pro Pro Gly Gln Gly Val Pro 50 55 60 Leu Asn Ala Asn Ser Thr Pro Ala Gln Asn Ala Gly Tyr Trp Arg Arg 65 70 75 80 Gln Asp Arg Lys Ile Asn Thr Gly Asn Gly Ile Lys Gln Leu Ala Pro 85 90 95 Arg Trp Tyr Phe Tyr Tyr Thr Gly Thr Gly Pro Glu Ala Ala Leu Pro 100 105 110 Phe Arg Ala Val Lys Asp Gly Ile Val Trp Val His Glu Asp Gly Ala 115 120 125 Thr Asp Ala Pro Ser Thr Phe Gly Thr Arg Asn Pro Asn Asn Asp Ser 130 135 140 Ala Ile Val Thr Gln Phe Ala Pro Gly Thr Lys Leu Pro Lys Asn Phe 145 150 155 160 His Ile Glu Gly Thr Gly Gly Asn Ser Gln Ser Ser Ser Arg Ala Ser 165 170 175 Ser Leu Ser Arg Asn Ser Ser Arg Ser Ser Ser Gln Gly Ser Arg Ser 180 185 190 Gly Asn Ser Thr Arg Gly Thr Ser Pro Gly Pro Ser Gly Ile Gly Ala 195 200 205 Val Gly Gly Asp Leu Leu Tyr Leu Asp Leu Leu Asn Arg Leu Gln Ala 210 215 220 Leu Glu Ser Gly Lys Val Lys Gln Ser Gln Pro Lys Val Ile Thr Lys 225 230 235 240 Lys Asp Ala Ala Ala Ala Lys Asn Lys Met Arg His Lys Arg Thr Ser 245 250 255 Thr Lys Ser Phe Asn Met Val Gln Ala Phe Gly Leu Arg Gly Pro Gly 260 265 270 Asp Leu Gln Gly Asn Phe Gly Asp Leu Gln Leu Asn Lys Leu Gly Thr 275 280 285 Glu Asp Pro Arg Trp Pro Gln Ile Ala Glu Leu Ala Pro Thr Ala Ser 290 295 300 Ala Phe Met Gly Met Ser Gln Phe Lys Leu Thr His Gln Asn Asn Asp 305 310 315 320 Asp His Gly Asn Pro Val Tyr Phe Leu Arg Tyr Ser Gly Ala Ile Lys 325 330 335 Leu Asp Pro Lys Asn Pro Asn Tyr Asn Lys Trp Leu Glu Leu Leu Glu 340 345 350 Gln Asn Ile Asp Ala Tyr Lys Thr Phe Pro Lys Lys Glu Lys Lys Gln 355 360 365 Lys Ala Pro Lys Glu Glu Ser Thr Asp Gln Met Ser Glu Pro Pro Lys 370 375 380 Glu Gln Arg Val Gln Gly Ser Ile Thr Gln Arg Thr Arg Thr Arg Pro 385 390 395 400 Ser Val Gln Pro Gly Pro Met Ile Asp Val Asn Thr Asp 405 410 <![CDATA[<210> 6]]> <![CDATA[<211> 1255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> SARS-CoV 病毒]]> <![CDATA[<400> 6]]> Met Phe Ile Phe Leu Leu Phe Leu Thr Leu Thr Ser Gly Ser Asp Leu 1 5 10 15 Asp Arg Cys Thr Thr Phe Asp Asp Val Gln Ala Pro Asn Tyr Thr Gln 20 25 30 His Thr Ser Ser Met Arg Gly Val Tyr Tyr Pro Asp Glu Ile Phe Arg 35 40 45 Ser Asp Thr Leu Tyr Leu Thr Gln Asp Leu Phe Leu Pro Phe Tyr Ser 50 55 60 Asn Val Thr Gly Phe His Thr Ile Asn His Thr Phe Gly Asn Pro Val 65 70 75 80 Ile Pro Phe Lys Asp Gly Ile Tyr Phe Ala Ala Thr Glu Lys Ser Asn 85 90 95 Val Val Arg Gly Trp Val Phe Gly Ser Thr Met Asn Asn Lys Ser Gln 100 105 110 Ser Val Ile Ile Ile Asn Asn Ser Thr Asn Val Val Ile Arg Ala Cys 115 120 125 Asn Phe Glu Leu Cys Asp Asn Pro Phe Phe Ala Val Ser Lys Pro Met 130 135 140 Gly Thr Gln Thr His Thr Met Ile Phe Asp Asn Ala Phe Asn Cys Thr 145 150 155 160 Phe Glu Tyr Ile Ser Asp Ala Phe Ser Leu Asp Val Ser Glu Lys Ser 165 170 175 Gly Asn Phe Lys His Leu Arg Glu Phe Val Phe Lys Asn Lys Asp Gly 180 185 190 Phe Leu Tyr Val Tyr Lys Gly Tyr Gln Pro Ile Asp Val Val Arg Asp 195 200 205 Leu Pro Ser Gly Phe Asn Thr Leu Lys Pro Ile Phe Lys Leu Pro Leu 210 215 220 Gly Ile Asn Ile Thr Asn Phe Arg Ala Ile Leu Thr Ala Phe Ser Pro 225 230 235 240 Ala Gln Asp Ile Trp Gly Thr Ser Ala Ala Ala Tyr Phe Val Gly Tyr 245 250 255 Leu Lys Pro Thr Thr Phe Met Leu Lys Tyr Asp Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ser Gln Asn Pro Leu Ala Glu Leu Lys Cys 275 280 285 Ser Val Lys Ser Phe Glu Ile Asp Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Val Pro Ser Gly Asp Val Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser 325 330 335 Val Tyr Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Met Gly Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser 420 425 430 Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu 435 440 445 Arg Pro Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly 450 455 460 Lys Pro Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp 465 470 475 480 Tyr Gly Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val 485 490 495 Val Val Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly 500 505 510 Pro Lys Leu Ser Thr Asp Leu Ile Lys Asn Gln Cys Val Asn Phe Asn 515 520 525 Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Pro Ser Ser Lys Arg 530 535 540 Phe Gln Pro Phe Gln Gln Phe Gly Arg Asp Val Ser Asp Phe Thr Asp 545 550 555 560 Ser Val Arg Asp Pro Lys Thr Ser Glu Ile Leu Asp Ile Ser Pro Cys 565 570 575 Ala Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Ala Ser Ser 580 585 590 Glu Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Asp Val Ser Thr 595 600 605 Ala Ile His Ala Asp Gln Leu Thr Pro Ala Trp Arg Ile Tyr Ser Thr 610 615 620 Gly Asn Asn Val Phe Gln Thr Gln Ala Gly Cys Leu Ile Gly Ala Glu 625 630 635 640 His Val Asp Thr Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile 645 650 655 Cys Ala Ser Tyr His Thr Val Ser Leu Leu Arg Ser Thr Ser Gln Lys 660 665 670 Ser Ile Val Ala Tyr Thr Met Ser Leu Gly Ala Asp Ser Ser Ile Ala 675 680 685 Tyr Ser Asn Asn Thr Ile Ala Ile Pro Thr Asn Phe Ser Ile Ser Ile 690 695 700 Thr Thr Glu Val Met Pro Val Ser Met Ala Lys Thr Ser Val Asp Cys 705 710 715 720 Asn Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ala Asn Leu Leu Leu 725 730 735 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Ser Gly Ile 740 745 750 Ala Ala Glu Gln Asp Arg Asn Thr Arg Glu Val Phe Ala Gln Val Lys 755 760 765 Gln Met Tyr Lys Thr Pro Thr Leu Lys Tyr Phe Gly Gly Phe Asn Phe 770 775 780 Ser Gln Ile Leu Pro Asp Pro Leu Lys Pro Thr Lys Arg Ser Phe Ile 785 790 795 800 Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Met 805 810 815 Lys Gln Tyr Gly Glu Cys Leu Gly Asp Ile Asn Ala Arg Asp Leu Ile 820 825 830 Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr 835 840 845 Asp Asp Met Ile Ala Ala Tyr Thr Ala Ala Leu Val Ser Gly Thr Ala 850 855 860 Thr Ala Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe 865 870 875 880 Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn 885 890 895 Val Leu Tyr Glu Asn Gln Lys Gln Ile Ala Asn Gln Phe Asn Lys Ala 900 905 910 Ile Ser Gln Ile Gln Glu Ser Leu Thr Thr Thr Ser Thr Ala Leu Gly 915 920 925 Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu 930 935 940 Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn 945 950 955 960 Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp 965 970 975 Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln 980 985 990 Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala 995 1000 1005 Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp 1010 1015 1020 Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ala Ala 1025 1030 1035 Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ser Gln 1040 1045 1050 Glu Arg Asn Phe Thr Thr Ala Pro Ala Ile Cys His Glu Gly Lys 1055 1060 1065 Ala Tyr Phe Pro Arg Glu Gly Val Phe Val Phe Asn Gly Thr Ser 1070 1075 1080 Trp Phe Ile Thr Gln Arg Asn Phe Phe Ser Pro Gln Ile Ile Thr 1085 1090 1095 Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly 1100 1105 1110 Ile Ile Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp 1115 1120 1125 Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser 1130 1135 1140 Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val 1145 1150 1155 Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys 1160 1165 1170 Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr 1175 1180 1185 Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Val Trp Leu Gly Phe Ile 1190 1195 1200 Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Leu Leu Cys Cys 1205 1210 1215 Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Ala Cys Ser Cys Gly 1220 1225 1230 Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys 1235 1240 1245 Gly Val Lys Leu His Tyr Thr 1250 1255 <![CDATA[<210> 7]]> <![CDATA[<211> 1281]]> <![CDATA[<212> PRT]]> <![CDATA[<213> SARS-CoV-2 病毒]]> <![CDATA[<400> 7]]> 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 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 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 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 Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 290 295 300 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 305 310 315 320 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 325 330 335 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 340 345 350 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 355 360 365 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 370 375 380 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 385 390 395 400 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 405 410 415 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 420 425 430 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 435 440 445 Gly Gly Asn Tyr Asn Tyr Leu Tyr Leu Tyr Arg Leu Phe Arg Lys Ser 450 455 460 Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala 465 470 475 480 Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro 485 490 495 Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro 500 505 510 Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr 515 520 525 Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val 530 535 540 Asn Phe Asn Phe Asn Gly Leu Thr Leu Thr Gly Thr Gly Val Leu Thr 545 550 555 560 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 565 570 575 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 580 585 590 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 595 600 605 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 610 615 620 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 625 630 635 640 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 645 650 655 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 660 665 670 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 675 680 685 Arg Arg Ala Arg Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 690 695 700 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 705 710 715 720 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 725 730 735 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 740 745 750 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 755 760 765 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 770 775 780 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 785 790 795 800 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 805 810 815 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 820 825 830 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 835 840 845 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 850 855 860 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 865 870 875 880 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 885 890 895 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 900 905 910 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 915 920 925 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 930 935 940 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 945 950 955 960 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 965 970 975 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 980 985 990 Lys Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 995 1000 1005 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala 1010 1015 1020 Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu 1025 1030 1035 Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly 1040 1045 1050 Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val 1055 1060 1065 Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr 1070 1075 1080 Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg 1085 1090 1095 Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln 1100 1105 1110 Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe 1115 1120 1125 Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr 1130 1135 1140 Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu 1145 1150 1155 Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu 1160 1165 1170 Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys 1175 1180 1185 Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser 1190 1195 1200 Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 1205 1210 1215 Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala 1220 1225 1230 Ile Val Met Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys 1235 1240 1245 Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe 1250 1255 1260 Asp Glu Asp Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu 1265 1270 1275 His Tyr Thr 1280 <![CDATA[<210> 8]]> <![CDATA[<211> 1353]]> <![CDATA[<212> PRT]]> <![CDATA[<213> MERS-CoV 病毒]]> <![CDATA[<400> 8]]> Met Ile His Ser Val Phe Leu Leu Met Phe Leu Leu Thr Pro Thr Glu 1 5 10 15 Ser Tyr Val Asp Val Gly Pro Asp Ser Val Lys Ser Ala Cys Ile Glu 20 25 30 Val Asp Ile Gln Gln Thr Phe Phe Asp Lys Thr Trp Pro Arg Pro Ile 35 40 45 Asp Val Ser Lys Ala Asp Gly Ile Ile Tyr Pro Gln Gly Arg Thr Tyr 50 55 60 Ser Asn Ile Thr Ile Thr Tyr Gln Gly Leu Phe Pro Tyr Gln Gly Asp 65 70 75 80 His Gly Asp Met Tyr Val Tyr Ser Ala Gly His Ala Thr Gly Thr Thr 85 90 95 Pro Gln Lys Leu Phe Val Ala Asn Tyr Ser Gln Asp Val Lys Gln Phe 100 105 110 Ala Asn Gly Phe Val Val Arg Ile Gly Ala Ala Ala Asn Ser Thr Gly 115 120 125 Thr Val Ile Ile Ser Pro Ser Thr Ser Ala Thr Ile Arg Lys Ile Tyr 130 135 140 Pro Ala Phe Met Leu Gly Ser Ser Val Gly Asn Phe Ser Asp Gly Lys 145 150 155 160 Met Gly Arg Phe Phe Asn His Thr Leu Val Leu Leu Pro Asp Gly Cys 165 170 175 Gly Thr Leu Leu Arg Ala Phe Tyr Cys Ile Leu Glu Pro Arg Ser Gly 180 185 190 Asn His Cys Pro Ala Gly Asn Ser Tyr Thr Ser Phe Ala Thr Tyr His 195 200 205 Thr Pro Ala Thr Asp Cys Ser Asp Gly Asn Tyr Asn Arg Asn Ala Ser 210 215 220 Leu Asn Ser Phe Lys Glu Tyr Phe Asn Leu Arg Asn Cys Thr Phe Met 225 230 235 240 Tyr Thr Tyr Asn Ile Thr Glu Asp Glu Ile Leu Glu Trp Phe Gly Ile 245 250 255 Thr Gln Thr Ala Gln Gly Val His Leu Phe Ser Ser Arg Tyr Val Asp 260 265 270 Leu Tyr Gly Gly Asn Met Phe Gln Phe Ala Thr Leu Pro Val Tyr Asp 275 280 285 Thr Ile Lys Tyr Tyr Ser Ile Ile Pro His Ser Ile Arg Ser Ile Gln 290 295 300 Ser Asp Arg Lys Ala Trp Ala Ala Phe Tyr Val Tyr Lys Leu Gln Pro 305 310 315 320 Leu Thr Phe Leu Leu Asp Phe Ser Val Asp Gly Tyr Ile Arg Arg Ala 325 330 335 Ile Asp Cys Gly Phe Asn Asp Leu Ser Gln Leu His Cys Ser Tyr Glu 340 345 350 Ser Phe Asp Val Glu Ser Gly Val Tyr Ser Val Ser Ser Phe Glu Ala 355 360 365 Lys Pro Ser Gly Ser Val Val Glu Gln Ala Glu Gly Val Glu Cys Asp 370 375 380 Phe Ser Pro Leu Leu Ser Gly Thr Pro Pro Gln Val Tyr Asn Phe Lys 385 390 395 400 Arg Leu Val Phe Thr Asn Cys Asn Tyr Asn Leu Thr Lys Leu Leu Ser 405 410 415 Leu Phe Ser Val Asn Asp Phe Thr Cys Ser Gln Ile Ser Pro Ala Ala 420 425 430 Ile Ala Ser Asn Cys Tyr Ser Ser Leu Ile Leu Asp Tyr Phe Ser Tyr 435 440 445 Pro Leu Ser Met Lys Ser Asp Leu Ser Val Ser Ser Ala Gly Pro Ile 450 455 460 Ser Gln Phe Asn Tyr Lys Gln Ser Phe Ser Asn Pro Thr Cys Leu Ile 465 470 475 480 Leu Ala Thr Val Pro His Asn Leu Thr Thr Ile Thr Lys Pro Leu Lys 485 490 495 Tyr Ser Tyr Ile Asn Lys Cys Ser Arg Leu Leu Ser Asp Asp Arg Thr 500 505 510 Glu Val Pro Gln Leu Val Asn Ala Asn Gln Tyr Ser Pro Cys Val Ser 515 520 525 Ile Val Pro Ser Thr Val Trp Glu Asp Gly Asp Tyr Tyr Arg Lys Gln 530 535 540 Leu Ser Pro Leu Glu Gly Gly Gly Trp Leu Val Ala Ser Gly Ser Thr 545 550 555 560 Val Ala Met Thr Glu Gln Leu Gln Met Gly Phe Gly Ile Thr Val Gln 565 570 575 Tyr Gly Thr Asp Thr Asn Ser Val Cys Pro Lys Leu Glu Phe Ala Asn 580 585 590 Asp Thr Lys Ile Ala Ser Gln Leu Gly Asn Cys Val Glu Tyr Ser Leu 595 600 605 Tyr Gly Val Ser Gly Arg Gly Val Phe Gln Asn Cys Thr Ala Val Gly 610 615 620 Val Arg Gln Gln Arg Phe Val Tyr Asp Ala Tyr Gln Asn Leu Val Gly 625 630 635 640 Tyr Tyr Ser Asp Asp Gly Asn Tyr Tyr Cys Leu Arg Ala Cys Val Ser 645 650 655 Val Pro Val Ser Val Ile Tyr Asp Lys Glu Thr Lys Thr His Ala Thr 660 665 670 Leu Phe Gly Ser Val Ala Cys Glu His Ile Ser Ser Thr Met Ser Gln 675 680 685 Tyr Ser Arg Ser Thr Arg Ser Met Leu Lys Arg Arg Asp Ser Thr Tyr 690 695 700 Gly Pro Leu Gln Thr Pro Val Gly Cys Val Leu Gly Leu Val Asn Ser 705 710 715 720 Ser Leu Phe Val Glu Asp Cys Lys Leu Pro Leu Gly Gln Ser Leu Cys 725 730 735 Ala Leu Pro Asp Thr Pro Ser Thr Leu Thr Pro Arg Ser Val Arg Ser 740 745 750 Val Pro Gly Glu Met Arg Leu Ala Ser Ile Ala Phe Asn His Pro Ile 755 760 765 Gln Val Asp Gln Leu Asn Ser Ser Tyr Phe Lys Leu Ser Ile Pro Thr 770 775 780 Asn Phe Ser Phe Gly Val Thr Gln Glu Tyr Ile Gln Thr Thr Ile Gln 785 790 795 800 Lys Val Thr Val Asp Cys Lys Gln Tyr Val Cys Asn Gly Phe Gln Lys 805 810 815 Cys Glu Gln Leu Leu Arg Glu Tyr Gly Gln Phe Cys Ser Lys Ile Asn 820 825 830 Gln Ala Leu His Gly Ala Asn Leu Arg Gln Asp Asp Ser Val Arg Asn 835 840 845 Leu Phe Ala Ser Val Lys Ser Ser Gln Ser Ser Pro Ile Ile Pro Gly 850 855 860 Phe Gly Gly Asp Phe Asn Leu Thr Leu Leu Glu Pro Val Ser Ile Ser 865 870 875 880 Thr Gly Ser Arg Ser Ala Arg Ser Ala Ile Glu Asp Leu Leu Phe Asp 885 890 895 Lys Val Thr Ile Ala Asp Pro Gly Tyr Met Gln Gly Tyr Asp Asp Cys 900 905 910 Met Gln Gln Gly Pro Ala Ser Ala Arg Asp Leu Ile Cys Ala Gln Tyr 915 920 925 Val Ala Gly Tyr Lys Val Leu Pro Pro Leu Met Asp Val Asn Met Glu 930 935 940 Ala Ala Tyr Thr Ser Ser Leu Leu Gly Ser Ile Ala Gly Val Gly Trp 945 950 955 960 Thr Ala Gly Leu Ser Ser Phe Ala Ala Ile Pro Phe Ala Gln Ser Ile 965 970 975 Phe Tyr Arg Leu Asn Gly Val Gly Ile Thr Gln Gln Val Leu Ser Glu 980 985 990 Asn Gln Lys Leu Ile Ala Asn Lys Phe Asn Gln Ala Leu Gly Ala Met 995 1000 1005 Gln Thr Gly Phe Thr Thr Thr Asn Glu Ala Phe Gln Lys Val Gln 1010 1015 1020 Asp Ala Val Asn Asn Asn Ala Gln Ala Leu Ser Lys Leu Ala Ser 1025 1030 1035 Glu Leu Ser Asn Thr Phe Gly Ala Ile Ser Ala Ser Ile Gly Asp 1040 1045 1050 Ile Ile Gln Arg Leu Asp Val Leu Glu Gln Asp Ala Gln Ile Asp 1055 1060 1065 Arg Leu Ile Asn Gly Arg Leu Thr Thr Leu Asn Ala Phe Val Ala 1070 1075 1080 Gln Gln Leu Val Arg Ser Glu Ser Ala Ala Leu Ser Ala Gln Leu 1085 1090 1095 Ala Lys Asp Lys Val Asn Glu Cys Val Lys Ala Gln Ser Lys Arg 1100 1105 1110 Ser Gly Phe Cys Gly Gln Gly Thr His Ile Val Ser Phe Val Val 1115 1120 1125 Asn Ala Pro Asn Gly Leu Tyr Phe Met His Val Gly Tyr Tyr Pro 1130 1135 1140 Ser Asn His Ile Glu Val Val Ser Ala Tyr Gly Leu Cys Asp Ala 1145 1150 1155 Ala Asn Pro Thr Asn Cys Ile Ala Pro Val Asn Gly Tyr Phe Ile 1160 1165 1170 Lys Thr Asn Asn Thr Arg Ile Val Asp Glu Trp Ser Tyr Thr Gly 1175 1180 1185 Ser Ser Phe Tyr Ala Pro Glu Pro Ile Thr Ser Leu Asn Thr Lys 1190 1195 1200 Tyr Val Ala Pro Gln Val Thr Tyr Gln Asn Ile Ser Thr Asn Leu 1205 1210 1215 Pro Pro Pro Leu Leu Gly Asn Ser Thr Gly Ile Asp Phe Gln Asp 1220 1225 1230 Glu Leu Asp Glu Phe Phe Lys Asn Val Ser Thr Ser Ile Pro Asn 1235 1240 1245 Phe Gly Ser Leu Thr Gln Ile Asn Thr Thr Leu Leu Asp Leu Thr 1250 1255 1260 Tyr Glu Met Leu Ser Leu Gln Gln Val Val Lys Ala Leu Asn Glu 1265 1270 1275 Ser Tyr Ile Asp Leu Lys Glu Leu Gly Asn Tyr Thr Tyr Tyr Asn 1280 1285 1290 Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Val 1295 1300 1305 Ala Leu Ala Leu Cys Val Phe Phe Ile Leu Cys Cys Thr Gly Cys 1310 1315 1320 Gly Thr Asn Cys Met Gly Lys Leu Lys Cys Asn Arg Cys Cys Asp 1325 1330 1335 Arg Tyr Glu Glu Tyr Asp Leu Glu Pro His Lys Val His Val His 1340 1345 1350 <![CDATA[<210> 9]]> <![CDATA[<211> 1255]]> <![CDATA[<212> PRT]]> <![CDATA[<213> SARS-CoV 病毒]]> <![CDATA[<400> 9]]> Met Phe Ile Phe Leu Leu Phe Leu Thr Leu Thr Ser Gly Ser Asp Leu 1 5 10 15 Asp Arg Cys Thr Thr Phe Asp Asp Val Gln Ala Pro Asn Tyr Thr Gln 20 25 30 His Thr Ser Ser Met Arg Gly Val Tyr Tyr Pro Asp Glu Ile Phe Arg 35 40 45 Ser Asp Thr Leu Tyr Leu Thr Gln Asp Leu Phe Leu Pro Phe Tyr Ser 50 55 60 Asn Val Thr Gly Phe His Thr Ile Asn His Thr Phe Asp Asn Pro Val 65 70 75 80 Ile Pro Phe Lys Asp Gly Ile Tyr Phe Ala Ala Thr Glu Lys Ser Asn 85 90 95 Val Val Arg Gly Trp Val Phe Gly Ser Thr Met Asn Asn Lys Ser Gln 100 105 110 Ser Val Ile Ile Ile Asn Asn Ser Thr Asn Val Val Ile Arg Ala Cys 115 120 125 Asn Phe Glu Leu Cys Asp Asn Pro Phe Phe Ala Val Ser Lys Pro Met 130 135 140 Gly Thr Gln Thr His Thr Met Ile Phe Asp Asn Ala Phe Asn Cys Thr 145 150 155 160 Phe Glu Tyr Ile Ser Asp Ala Phe Ser Leu Asp Val Ser Glu Lys Ser 165 170 175 Gly Asn Phe Lys His Leu Arg Glu Phe Val Phe Lys Asn Lys Asp Gly 180 185 190 Phe Leu Tyr Val Tyr Lys Gly Tyr Gln Pro Ile Asp Val Val Arg Asp 195 200 205 Leu Pro Ser Gly Phe Asn Thr Leu Lys Pro Ile Phe Lys Leu Pro Leu 210 215 220 Gly Ile Asn Ile Thr Asn Phe Arg Ala Ile Leu Thr Ala Phe Ser Pro 225 230 235 240 Ala Gln Asp Thr Trp Gly Thr Ser Ala Ala Ala Tyr Phe Val Gly Tyr 245 250 255 Leu Lys Pro Thr Thr Phe Met Leu Lys Tyr Asp Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ser Gln Asn Pro Leu Ala Glu Leu Lys Cys 275 280 285 Ser Val Lys Ser Phe Glu Ile Asp Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Val Pro Ser Gly Asp Val Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser 325 330 335 Val Tyr Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Met Gly Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser 420 425 430 Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu 435 440 445 Arg Pro Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly 450 455 460 Lys Pro Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp 465 470 475 480 Tyr Gly Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val 485 490 495 Val Val Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly 500 505 510 Pro Lys Leu Ser Thr Asp Leu Ile Lys Asn Gln Cys Val Asn Phe Asn 515 520 525 Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Pro Ser Ser Lys Arg 530 535 540 Phe Gln Pro Phe Gln Gln Phe Gly Arg Asp Val Ser Asp Phe Thr Asp 545 550 555 560 Ser Val Arg Asp Pro Lys Thr Ser Glu Ile Leu Asp Ile Ser Pro Cys 565 570 575 Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Ala Ser Ser 580 585 590 Glu Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Asp Val Ser Thr 595 600 605 Ala Ile His Ala Asp Gln Leu Thr Pro Ala Trp Arg Ile Tyr Ser Thr 610 615 620 Gly Asn Asn Val Phe Gln Thr Gln Ala Gly Cys Leu Ile Gly Ala Glu 625 630 635 640 His Val Asp Thr Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile 645 650 655 Cys Ala Ser Tyr His Thr Val Ser Leu Leu Arg Ser Thr Ser Gln Lys 660 665 670 Ser Ile Val Ala Tyr Thr Met Ser Leu Gly Ala Asp Ser Ser Ile Ala 675 680 685 Tyr Ser Asn Asn Thr Ile Ala Ile Pro Thr Asn Phe Ser Ile Ser Ile 690 695 700 Thr Thr Glu Val Met Pro Val Ser Met Ala Lys Thr Ser Val Asp Cys 705 710 715 720 Asn Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ala Asn Leu Leu Leu 725 730 735 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Ser Gly Ile 740 745 750 Ala Ala Glu Gln Asp Arg Asn Thr Arg Glu Val Phe Ala Gln Val Lys 755 760 765 Gln Met Tyr Lys Thr Pro Thr Leu Lys Tyr Phe Gly Gly Phe Asn Phe 770 775 780 Ser Gln Ile Leu Pro Asp Pro Leu Lys Pro Thr Lys Arg Ser Phe Ile 785 790 795 800 Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Met 805 810 815 Lys Gln Tyr Gly Glu Cys Leu Gly Asp Ile Asn Ala Arg Asp Leu Ile 820 825 830 Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr 835 840 845 Asp Asp Met Ile Ala Ala Tyr Thr Ala Ala Leu Val Ser Gly Thr Ala 850 855 860 Thr Ala Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe 865 870 875 880 Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn 885 890 895 Val Leu Tyr Glu Asn Gln Lys Gln Ile Ala Asn Gln Phe Asn Lys Ala 900 905 910 Ile Ser Gln Ile Gln Glu Ser Leu Thr Thr Thr Ser Thr Ala Leu Gly 915 920 925 Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu 930 935 940 Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn 945 950 955 960 Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp 965 970 975 Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln 980 985 990 Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala 995 1000 1005 Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp 1010 1015 1020 Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ala Ala 1025 1030 1035 Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ser Gln 1040 1045 1050 Glu Arg Asn Phe Thr Thr Ala Pro Ala Ile Cys His Glu Gly Lys 1055 1060 1065 Ala Tyr Phe Pro Arg Glu Gly Val Phe Val Phe Asn Gly Thr Ser 1070 1075 1080 Trp Phe Ile Thr Gln Arg Asn Phe Phe Ser Pro Gln Ile Ile Thr 1085 1090 1095 Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly 1100 1105 1110 Ile Ile Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp 1115 1120 1125 Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser 1130 1135 1140 Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val 1145 1150 1155 Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys 1160 1165 1170 Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr 1175 1180 1185 Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Val Trp Leu Gly Phe Ile 1190 1195 1200 Ala Gly Leu Met Ala Ile Val Met Val Thr Ile Leu Leu Cys Cys 1205 1210 1215 Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Ala Cys Ser Cys Gly 1220 1225 1230 Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys 1235 1240 1245 Gly Val Lys Leu His Tyr Thr 1250 1255 <![CDATA[<210> 10]]> <![CDATA[<211> 1351]]> <![CDATA[<212>]]> PRT <![CDATA[<213> HKU-CoV 病毒]]> <![CDATA[<400> 10]]> Met Phe Leu Ile Ile Phe Ile Leu Pro Thr Thr Leu Ala Val Ile Gly 1 5 10 15 Asp Phe Asn Cys Thr Asn Ser Phe Ile Asn Asp Tyr Asn Lys Thr Ile 20 25 30 Pro Arg Ile Ser Glu Asp Val Val Asp Val Ser Leu Gly Leu Gly Thr 35 40 45 Tyr Tyr Val Leu Asn Arg Val Tyr Leu Asn Thr Thr Leu Leu Phe Thr 50 55 60 Gly Tyr Phe Pro Lys Ser Gly Ala Asn Phe Arg Asp Leu Ala Leu Lys 65 70 75 80 Gly Ser Ile Tyr Leu Ser Thr Leu Trp Tyr Lys Pro Pro Phe Leu Ser 85 90 95 Asp Phe Asn Asn Gly Ile Phe Ser Lys Val Lys Asn Thr Lys Leu Tyr 100 105 110 Val Asn Asn Thr Leu Tyr Ser Glu Phe Ser Thr Ile Val Ile Gly Ser 115 120 125 Val Phe Val Asn Thr Ser Tyr Thr Ile Val Val Gln Pro His Asn Gly 130 135 140 Ile Leu Glu Ile Thr Ala Cys Gln Tyr Thr Met Cys Glu Tyr Pro His 145 150 155 160 Thr Val Cys Lys Ser Lys Gly Ser Ile Arg Asn Glu Ser Trp His Ile 165 170 175 Asp Ser Ser Glu Pro Leu Cys Leu Phe Lys Lys Asn Phe Thr Tyr Asn 180 185 190 Val Ser Ala Asp Trp Leu Tyr Phe His Phe Tyr Gln Glu Arg Gly Val 195 200 205 Phe Tyr Ala Tyr Tyr Ala Asp Val Gly Met Pro Thr Thr Phe Leu Phe 210 215 220 Ser Leu Tyr Leu Gly Thr Ile Leu Ser His Tyr Tyr Val Met Pro Leu 225 230 235 240 Thr Cys Asn Ala Ile Ser Ser Asn Thr Asp Asn Glu Thr Leu Glu Tyr 245 250 255 Trp Val Thr Pro Leu Ser Arg Arg Gln Tyr Leu Leu Asn Phe Asp Glu 260 265 270 His Gly Val Ile Thr Asn Ala Val Asp Cys Ser Ser Ser Phe Leu Ser 275 280 285 Glu Ile Gln Cys Lys Thr Gln Ser Phe Ala Pro Asn Thr Gly Val Tyr 290 295 300 Asp Leu Ser Gly Phe Thr Val Lys Pro Val Ala Thr Val Tyr Arg Arg 305 310 315 320 Ile Pro Asn Leu Pro Asp Cys Asp Ile Asp Asn Trp Leu Asn Asn Val 325 330 335 Ser Val Pro Ser Pro Leu Asn Trp Glu Arg Arg Ile Phe Ser Asn Cys 340 345 350 Asn Phe Asn Leu Ser Thr Leu Leu Arg Leu Val His Val Asp Ser Phe 355 360 365 Ser Cys Asn Asn Leu Asp Lys Ser Lys Ile Phe Gly Ser Cys Phe Asn 370 375 380 Ser Ile Thr Val Asp Lys Phe Ala Ile Pro Asn Arg Arg Arg Asp Asp 385 390 395 400 Leu Gln Leu Gly Ser Ser Gly Phe Leu Gln Ser Ser Asn Tyr Lys Ile 405 410 415 Asp Ile Ser Ser Ser Ser Cys Gln Leu Tyr Tyr Ser Leu Pro Leu Val 420 425 430 Asn Val Thr Ile Asn Asn Phe Asn Pro Ser Ser Trp Asn Arg Arg Tyr 435 440 445 Gly Phe Gly Ser Phe Asn Leu Ser Ser Tyr Asp Val Val Tyr Ser Asp 450 455 460 His Cys Phe Ser Val Asn Ser Asp Phe Cys Pro Cys Ala Asp Pro Ser 465 470 475 480 Val Val Asn Ser Cys Ala Lys Ser Lys Pro Pro Ser Ala Ile Cys Pro 485 490 495 Ala Gly Thr Lys Tyr Arg His Cys Asp Leu Asp Thr Thr Leu Tyr Val 500 505 510 Lys Asn Trp Cys Arg Cys Ser Cys Leu Pro Asp Pro Ile Ser Thr Tyr 515 520 525 Ser Pro Asn Thr Cys Pro Gln Lys Lys Val Val Val Gly Ile Gly Glu 530 535 540 His Cys Pro Gly Leu Gly Ile Asn Glu Glu Lys Cys Gly Thr Gln Leu 545 550 555 560 Asn His Ser Ser Cys Phe Cys Ser Pro Asp Ala Phe Leu Gly Trp Ser 565 570 575 Phe Asp Ser Cys Ile Ser Asn Asn Arg Cys Asn Ile Phe Ser Asn Phe 580 585 590 Ile Phe Asn Gly Ile Asn Ser Gly Thr Thr Cys Ser Asn Asp Leu Leu 595 600 605 Tyr Ser Asn Thr Glu Ile Ser Thr Gly Val Cys Val Asn Tyr Asp Leu 610 615 620 Tyr Gly Ile Thr Gly Gln Gly Ile Phe Lys Glu Val Ser Ala Ala Tyr 625 630 635 640 Tyr Asn Asn Trp Gln Asn Leu Leu Tyr Asp Ser Asn Gly Asn Ile Ile 645 650 655 Gly Phe Lys Asp Phe Leu Thr Asn Lys Thr Tyr Thr Ile Leu Pro Cys 660 665 670 Tyr Ser Gly Arg Val Ser Ala Ala Phe Tyr Gln Asn Ser Ser Ser Pro 675 680 685 Ala Leu Leu Tyr Arg Asn Leu Lys Cys Ser Tyr Val Leu Asn Asn Ile 690 695 700 Ser Phe Ile Ser Gln Pro Phe Tyr Phe Asp Ser Tyr Leu Gly Cys Val 705 710 715 720 Leu Asn Ala Val Asn Leu Thr Ser Tyr Ser Val Ser Ser Cys Asp Leu 725 730 735 Arg Met Gly Ser Gly Phe Cys Ile Asp Tyr Ala Leu Pro Ser Ser Arg 740 745 750 Arg Lys Arg Arg Gly Ile Ser Ser Pro Tyr Arg Phe Val Thr Phe Glu 755 760 765 Pro Phe Asn Val Ser Phe Val Asn Asp Ser Val Glu Thr Val Gly Gly 770 775 780 Leu Phe Glu Ile Gln Ile Pro Thr Asn Phe Thr Ile Ala Gly His Glu 785 790 795 800 Glu Phe Ile Gln Thr Ser Ser Pro Lys Val Thr Ile Asp Cys Ser Ala 805 810 815 Phe Val Cys Ser Asn Tyr Ala Ala Cys His Asp Leu Leu Ser Glu Tyr 820 825 830 Gly Thr Phe Cys Asp Asn Ile Asn Ser Ile Leu Asn Glu Val Asn Asp 835 840 845 Leu Leu Asp Ile Thr Gln Leu Gln Val Ala Asn Ala Leu Met Gln Gly 850 855 860 Val Thr Leu Ser Ser Asn Leu Asn Thr Asn Leu His Ser Asp Val Asp 865 870 875 880 Asn Ile Asp Phe Lys Ser Leu Leu Gly Cys Leu Gly Ser Gln Cys Gly 885 890 895 Ser Ser Ser Arg Ser Leu Leu Glu Asp Leu Leu Phe Asn Lys Val Lys 900 905 910 Leu Ser Asp Val Gly Phe Val Glu Ala Tyr Asn Asn Cys Thr Gly Gly 915 920 925 Ser Glu Ile Arg Asp Leu Leu Cys Val Gln Ser Phe Asn Gly Ile Lys 930 935 940 Val Leu Pro Pro Ile Leu Ser Glu Thr Gln Ile Ser Gly Tyr Thr Thr 945 950 955 960 Ala Ala Thr Val Ala Ala Met Phe Pro Pro Trp Ser Ala Ala Ala Gly 965 970 975 Val Pro Phe Ser Leu Asn Val Gln Tyr Arg Ile Asn Gly Leu Gly Val 980 985 990 Thr Met Asp Val Leu Asn Lys Asn Gln Lys Leu Ile Ala Asn Ala Phe 995 1000 1005 Asn Lys Ala Leu Leu Ser Ile Gln Asn Gly Phe Thr Ala Thr Asn 1010 1015 1020 Ser Ala Leu Ala Lys Ile Gln Ser Val Val Asn Ala Asn Ala Gln 1025 1030 1035 Ala Leu Asn Ser Leu Leu Gln Gln Leu Phe Asn Lys Phe Gly Ala 1040 1045 1050 Ile Ser Ser Ser Leu Gln Glu Ile Leu Ser Arg Leu Asp Asn Leu 1055 1060 1065 Glu Ala Gln Val Gln Ile Asp Arg Leu Ile Asn Gly Arg Leu Thr 1070 1075 1080 Ala Leu Asn Ala Tyr Val Ser Gln Gln Leu Ser Asp Ile Thr Leu 1085 1090 1095 Ile Lys Ala Gly Ala Ser Arg Ala Ile Glu Lys Val Asn Glu Cys 1100 1105 1110 Val Lys Ser Gln Ser Pro Arg Ile Asn Phe Cys Gly Asn Gly Asn 1115 1120 1125 His Ile Leu Ser Leu Val Gln Asn Ala Pro Tyr Gly Leu Leu Phe 1130 1135 1140 Ile His Phe Ser Tyr Lys Pro Thr Ser Phe Lys Thr Val Leu Val 1145 1150 1155 Ser Pro Gly Leu Cys Leu Ser Gly Asp Arg Gly Ile Ala Pro Lys 1160 1165 1170 Gln Gly Tyr Phe Ile Lys Gln Asn Asp Ser Trp Met Phe Thr Gly 1175 1180 1185 Ser Ser Tyr Tyr Tyr Pro Glu Pro Ile Ser Asp Lys Asn Val Val 1190 1195 1200 Phe Met Asn Ser Cys Ser Val Asn Phe Thr Lys Ala Pro Phe Ile 1205 1210 1215 Tyr Leu Asn Asn Ser Ile Pro Asn Leu Ser Asp Phe Glu Ala Glu 1220 1225 1230 Leu Ser Leu Trp Phe Lys Asn His Thr Ser Ile Ala Pro Asn Leu 1235 1240 1245 Thr Phe Asn Ser His Ile Asn Ala Thr Phe Leu Asp Leu Tyr Tyr 1250 1255 1260 Glu Met Asn Val Ile Gln Glu Ser Ile Lys Ser Leu Asn Ser Ser 1265 1270 1275 Phe Ile Asn Leu Lys Glu Ile Gly Thr Tyr Glu Met Tyr Val Lys 1280 1285 1290 Trp Pro Trp Tyr Ile Trp Leu Leu Ile Val Ile Leu Phe Ile Ile 1295 1300 1305 Phe Leu Met Ile Leu Phe Phe Ile Cys Cys Cys Thr Gly Cys Gly 1310 1315 1320 Ser Ala Cys Phe Ser Lys Cys His Asn Cys Cys Asp Glu Tyr Gly 1325 1330 1335 Gly His Asn Asp Phe Val Ile Lys Ala Ser His Asp Asp 1340 1345 1350 <![CDATA[<210> 11]]> <![CDATA[<211> 1171]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 229E-CoV 病毒]]> <![CDATA[<400> 11]]> Met Phe Val Leu Leu Val Ala Tyr Ala Leu Leu His Ile Ala Gly Cys 1 5 10 15 Gln Thr Thr Asn Gly Thr Asn Thr Ser His Ser Val Cys Asn Gly Cys 20 25 30 Val Gly His Ser Glu Asn Val Phe Ala Val Glu Ser Gly Gly Tyr Ile 35 40 45 Pro Ser Asn Phe Ser Phe Asn Asn Trp Phe Leu Leu Thr Asn Thr Ser 50 55 60 Ser Val Val Asp Gly Val Val Arg Ser Phe Gln Pro Leu Leu Leu Asn 65 70 75 80 Cys Leu Trp Ser Val Ser Gly Ser Gln Phe Thr Thr Gly Phe Val Tyr 85 90 95 Phe Asn Gly Thr Gly Arg Gly Ala Cys Lys Gly Phe Tyr Ser Asn Ala 100 105 110 Ser Ser Asp Val Ile Arg Tyr Asn Ile Asn Phe Glu Glu Asn Leu Arg 115 120 125 Arg Gly Thr Ile Leu Phe Lys Thr Ser Tyr Gly Ala Val Val Phe Tyr 130 135 140 Cys Thr Asn Asn Thr Leu Val Ser Gly Asp Ala His Ile Pro Ser Gly 145 150 155 160 Thr Val Leu Gly Asn Phe Tyr Cys Phe Val Asn Thr Thr Ile Gly Asn 165 170 175 Glu Thr Thr Ser Ala Phe Val Gly Ala Leu Pro Lys Thr Val Arg Glu 180 185 190 Phe Val Ile Ser Arg Thr Gly His Phe Tyr Ile Asn Gly Tyr Arg Tyr 195 200 205 Phe Ser Leu Gly Asp Val Glu Ala Val Asn Phe Asn Val Thr Asn Ala 210 215 220 Ala Thr Ile Val Cys Thr Val Ala Leu Ala Ser Tyr Ala Asp Val Leu 225 230 235 240 Val Asn Val Ser Gln Thr Ala Ile Ala Asn Ile Ile Tyr Cys Asn Ser 245 250 255 Val Ile Asn Arg Leu Arg Cys Asp Gln Leu Ser Phe Asp Val Pro Asp 260 265 270 Gly Phe Tyr Ser Thr Ser Pro Ile Gln Pro Val Glu Leu Pro Met Ser 275 280 285 Ile Val Ser Leu Pro Val Tyr His Lys His Thr Phe Ile Val Leu His 290 295 300 Val Lys Phe Glu His Gln Arg Gly Pro Gly Lys Cys Tyr Asn Cys Arg 305 310 315 320 Pro Ser Val Ile Asn Ile Thr Leu Ala Asn Phe Asn Glu Thr Lys Gly 325 330 335 Pro Leu Cys Val Asp Thr Ser His Phe Thr Thr Gln Phe Val Asp Asn 340 345 350 Val Lys Leu Ala Arg Trp Ser Ala Ser Ile Asn Thr Gly Asn Cys Pro 355 360 365 Phe Ser Phe Gly Lys Val Asn Asn Phe Val Lys Phe Gly Ser Val Cys 370 375 380 Phe Ser Leu Lys Asp Ile Pro Gly Gly Cys Ala Met Pro Ile Met Ala 385 390 395 400 Asn Leu Val Asn His Lys Ser His Asn Ile Gly Ser Leu Tyr Val Ser 405 410 415 Trp Ser Asp Gly Asp Val Ile Thr Gly Val Pro Lys Pro Val Glu Gly 420 425 430 Val Ser Ser Phe Met Asn Val Thr Leu Asn Lys Cys Thr Lys Tyr Asn 435 440 445 Ile Tyr Asp Val Ser Gly Val Gly Val Ile Arg Ile Ser Asn Asp Thr 450 455 460 Phe Leu Asn Gly Ile Thr Tyr Thr Ser Thr Ser Gly Asn Leu Leu Gly 465 470 475 480 Phe Lys Asp Val Thr Asn Gly Thr Ile Tyr Ser Ile Thr Pro Cys Asn 485 490 495 Pro Pro Asp Gln Leu Val Val Tyr Gln Gln Ala Val Val Gly Ala Met 500 505 510 Leu Ser Glu Asn Phe Thr Ser Tyr Gly Phe Ser Asn Val Val Glu Met 515 520 525 Pro Lys Phe Phe Tyr Ala Ser Asn Gly Thr Tyr Asn Cys Thr Asp Ala 530 535 540 Val Leu Thr Tyr Ser Ser Phe Gly Val Cys Ala Asp Gly Ser Ile Ile 545 550 555 560 Ala Val Gln Pro Arg Asn Val Ser Tyr Asp Ser Val Ser Ala Ile Val 565 570 575 Thr Ala Asn Leu Ser Ile Pro Ser Asn Trp Thr Thr Ser Val Gln Val 580 585 590 Glu Tyr Leu Gln Ile Thr Ser Lys Pro Ile Val Val Asp Cys Ser Thr 595 600 605 Tyr Val Cys Asn Gly Asn Val Arg Cys Val Glu Leu Leu Lys Gln Tyr 610 615 620 Thr Ser Ala Cys Lys Thr Ile Glu Asp Ala Leu Arg Asn Ser Ala Met 625 630 635 640 Leu Glu Ser Ala Asp Val Ser Glu Met Leu Thr Phe Asp Lys Lys Ala 645 650 655 Phe Thr Leu Ala Asn Val Ser Ser Phe Gly Asp Tyr Asn Leu Ser Ser 660 665 670 Val Ile Pro Ser Leu Pro Arg Ser Gly Ser Arg Val Ala Gly Arg Ser 675 680 685 Ala Ile Glu Asp Ile Leu Phe Ser Lys Leu Val Thr Ser Gly Leu Gly 690 695 700 Thr Val Asp Ala Asp Tyr Lys Lys Cys Thr Lys Gly Leu Ser Ile Ala 705 710 715 720 Asp Leu Ala Cys Ala Gln Tyr Tyr Asn Gly Ile Met Val Leu Pro Gly 725 730 735 Val Ala Asp Ala Glu Arg Met Ala Met Tyr Thr Gly Ser Leu Ile Gly 740 745 750 Gly Ile Ala Leu Gly Gly Leu Thr Ser Ala Ala Ser Ile Pro Phe Ser 755 760 765 Leu Ala Ile Gln Ser Arg Leu Asn Tyr Val Ala Leu Gln Thr Asp Val 770 775 780 Leu Gln Glu Asn Gln Lys Ile Leu Ala Ala Ser Phe Asn Lys Ala Met 785 790 795 800 Thr Asn Ile Val Asp Ala Phe Thr Gly Val Asn Asp Ala Ile Thr Gln 805 810 815 Thr Ser Gln Ala Leu Gln Thr Val Ala Thr Ala Leu Asn Lys Ile Gln 820 825 830 Asp Val Val Asn Gln Gln Gly Asn Ser Leu Asn His Leu Thr Ser Gln 835 840 845 Leu Arg Gln Asn Phe Gln Ala Ile Ser Ser Ser Ile Gln Ala Ile Tyr 850 855 860 Asp Arg Leu Asp Ile Ile Gln Ala Asp Gln Gln Val Asp Arg Leu Ile 865 870 875 880 Thr Gly Arg Leu Ala Ala Leu Asn Val Phe Val Ser His Thr Leu Thr 885 890 895 Lys Tyr Thr Glu Val Arg Ala Ser Arg Gln Leu Ala Gln Gln Lys Val 900 905 910 Asn Glu Cys Val Lys Ser Gln Ser Lys Arg Tyr Gly Phe Cys Gly Asn 915 920 925 Gly Thr His Ile Phe Ser Leu Val Asn Ala Ala Pro Glu Gly Leu Val 930 935 940 Phe Leu His Thr Val Leu Leu Pro Thr Gln Tyr Lys Asp Val Glu Ala 945 950 955 960 Trp Ser Gly Leu Cys Val Asp Gly Ile Asn Gly Tyr Val Leu Arg Gln 965 970 975 Pro Asn Leu Ala Leu Tyr Lys Glu Gly Asn Tyr Tyr Arg Ile Thr Ser 980 985 990 Arg Ile Met Phe Glu Pro Arg Ile Pro Thr Ile Ala Asp Phe Val Gln 995 1000 1005 Ile Glu Asn Cys Asn Val Thr Phe Val Asn Ile Ser Arg Ser Glu 1010 1015 1020 Leu Gln Thr Ile Val Pro Glu Tyr Ile Asp Val Asn Lys Thr Leu 1025 1030 1035 Gln Glu Leu Ser Tyr Lys Leu Pro Asn Tyr Thr Val Pro Asp Leu 1040 1045 1050 Val Val Glu Gln Tyr Asn Gln Thr Ile Leu Asn Leu Thr Ser Glu 1055 1060 1065 Ile Ser Thr Leu Glu Asn Lys Ser Ala Glu Leu Asn Tyr Thr Val 1070 1075 1080 Gln Lys Leu Gln Thr Leu Ile Asp Asn Ile Asn Ser Thr Leu Val 1085 1090 1095 Asp Leu Lys Trp Leu Asn Arg Val Glu Thr Tyr Ile Lys Trp Pro 1100 1105 1110 Trp Trp Val Trp Leu Cys Ile Ser Val Val Leu Ile Phe Val Val 1115 1120 1125 Ser Met Leu Leu Leu Cys Cys Cys Ser Thr Gly Cys Cys Gly Phe 1130 1135 1140 Phe Ser Cys Phe Ala Ser Ser Ile Lys Gly Cys Cys Glu Ser Thr 1145 1150 1155 Lys Leu Pro Tyr Tyr Asp Val Glu Lys Ile His Ile Gln 1160 1165 1170 <![CDATA[<210> 12]]> <![CDATA[<211> 1356]]> <![CDATA[<212> PRT]]> <![CDATA[<213> NL63-CoV 病毒]]> <![CDATA[<400> 12]]> Met Lys Leu Phe Leu Ile Leu Leu Val Leu Pro Leu Ala Ser Cys Phe 1 5 10 15 Phe Thr Cys Asn Ser Asn Ala Asn Leu Ser Met Leu Gln Leu Gly Val 20 25 30 Pro Asp Asn Ser Ser Thr Ile Val Thr Gly Leu Leu Pro Thr His Trp 35 40 45 Ile Cys Ala Asn Gln Ser Thr Ser Val Tyr Ser Ala Asn Gly Phe Phe 50 55 60 Tyr Ile Asp Val Gly Asn His Arg Ser Ala Phe Ala Leu His Thr Gly 65 70 75 80 Tyr Tyr Asp Val Asn Gln Tyr Tyr Ile Tyr Val Thr Asn Glu Ile Gly 85 90 95 Leu Asn Ala Ser Val Thr Leu Lys Ile Cys Lys Phe Gly Ile Asn Thr 100 105 110 Thr Phe Asp Phe Leu Ser Asn Ser Ser Ser Ser Phe Asp Cys Ile Val 115 120 125 Asn Leu Leu Phe Thr Glu Gln Leu Gly Ala Pro Leu Gly Ile Thr Ile 130 135 140 Ser Gly Glu Thr Val Arg Leu His Leu Tyr Asn Val Thr Arg Thr Phe 145 150 155 160 Tyr Val Pro Ala Ala Tyr Lys Leu Thr Lys Leu Ser Val Lys Cys Tyr 165 170 175 Phe Asn Tyr Ser Cys Val Phe Ser Val Val Asn Ala Thr Val Thr Val 180 185 190 Asn Val Thr Thr His Asn Gly Arg Val Val Asn Tyr Thr Val Cys Asp 195 200 205 Asp Cys Asn Gly Tyr Thr Asp Asn Ile Phe Ser Val Gln Gln Asp Gly 210 215 220 Arg Ile Pro Asn Gly Phe Pro Phe Asn Asn Trp Phe Leu Leu Thr Asn 225 230 235 240 Gly Ser Thr Leu Val Asp Gly Val Ser Arg Leu Tyr Gln Pro Leu Arg 245 250 255 Leu Thr Cys Leu Trp Pro Val Pro Gly Leu Lys Ser Ser Thr Gly Phe 260 265 270 Val Tyr Phe Asn Ala Thr Gly Ser Asp Val Asn Cys Asn Gly Tyr Gln 275 280 285 His Asn Ser Val Ala Asp Val Met Arg Tyr Asn Leu Asn Phe Ser Ala 290 295 300 Asn Ser Val Asp Asn Leu Lys Ser Gly Val Ile Val Phe Lys Thr Leu 305 310 315 320 Gln Tyr Asp Val Leu Phe Tyr Cys Ser Asn Ser Ser Ser Gly Val Leu 325 330 335 Asp Thr Thr Ile Pro Phe Gly Pro Ser Ser Gln Pro Tyr Tyr Cys Phe 340 345 350 Ile Asn Ser Thr Ile Asn Thr Thr His Val Ser Thr Phe Val Gly Val 355 360 365 Leu Pro Pro Thr Val Arg Glu Ile Val Val Ala Arg Thr Gly Gln Phe 370 375 380 Tyr Ile Asn Gly Phe Lys Tyr Phe Asp Leu Gly Phe Ile Glu Ala Val 385 390 395 400 Asn Phe Asn Val Thr Thr Ala Ser Ala Thr Asp Phe Trp Thr Val Ala 405 410 415 Phe Ala Thr Phe Val Asp Val Leu Val Asn Val Ser Ala Thr Lys Ile 420 425 430 Gln Asn Leu Leu Tyr Cys Asp Ser Pro Phe Glu Lys Leu Gln Cys Glu 435 440 445 His Leu Gln Phe Gly Leu Gln Asp Gly Phe Tyr Ser Ala Asn Phe Leu 450 455 460 Asp Asp Asn Val Leu Pro Glu Thr Tyr Val Ala Leu Pro Ile Tyr Tyr 465 470 475 480 Gln His Thr Asp Ile Asn Phe Thr Ala Thr Ala Ser Phe Gly Gly Ser 485 490 495 Cys Tyr Val Cys Lys Pro His Gln Val Asn Ile Ser Leu Asn Gly Asn 500 505 510 Thr Ser Val Cys Val Arg Thr Ser His Phe Ser Ile Arg Tyr Ile Tyr 515 520 525 Asn Arg Val Lys Ser Gly Ser Pro Gly Asp Ser Ser Trp His Ile Tyr 530 535 540 Leu Lys Ser Gly Thr Cys Pro Phe Ser Phe Ser Lys Leu Asn Asn Phe 545 550 555 560 Gln Lys Phe Lys Thr Ile Cys Phe Ser Thr Val Ala Val Pro Gly Ser 565 570 575 Cys Asn Phe Pro Leu Glu Ala Thr Trp His Tyr Thr Ser Tyr Thr Ile 580 585 590 Val Gly Ala Leu Tyr Val Thr Trp Ser Glu Gly Asn Ser Ile Thr Gly 595 600 605 Val Pro Tyr Pro Val Ser Gly Ile Arg Glu Phe Ser Asn Leu Val Leu 610 615 620 Asn Asn Cys Thr Lys Tyr Asn Ile Tyr Asp Tyr Val Gly Thr Gly Ile 625 630 635 640 Ile Arg Ser Ser Asn Gln Ser Leu Ala Gly Gly Ile Thr Tyr Val Ser 645 650 655 Asn Ser Gly Asn Leu Leu Gly Phe Lys Asn Val Ser Thr Gly Asn Ile 660 665 670 Phe Ile Val Thr Pro Cys Asn Gln Pro Asp Gln Val Ala Val Tyr Gln 675 680 685 Gln Ser Ile Ile Gly Ala Met Thr Ala Val Asn Glu Ser Arg Tyr Gly 690 695 700 Leu Gln Asn Leu Leu Gln Leu Pro Asn Phe Tyr Tyr Val Ser Asn Gly 705 710 715 720 Gly Asn Asn Cys Thr Thr Ala Val Met Thr Tyr Ser Asn Phe Gly Ile 725 730 735 Cys Ala Asp Gly Ser Leu Ile Pro Val Arg Leu Arg Asn Ser Ser Asp 740 745 750 Asn Gly Ile Ser Ala Ile Ile Thr Ala Asn Leu Ser Ile Pro Ser Asn 755 760 765 Trp Thr Thr Ser Val Gln Val Glu Tyr Leu Gln Ile Thr Ser Ile Pro 770 775 780 Ile Val Val Asp Cys Ala Thr Tyr Val Cys Asn Gly Asn Pro Arg Cys 785 790 795 800 Lys Asn Leu Leu Lys Gln Tyr Thr Ser Ala Cys Lys Thr Ile Glu Asp 805 810 815 Ala Leu Arg Leu Ser Ala His Leu Glu Thr Asn Asp Val Ser Ser Met 820 825 830 Leu Thr Phe Asp Ser Asn Ala Phe Ser Leu Ala Asn Val Thr Ser Phe 835 840 845 Gly Asp Tyr Asn Leu Ser Ser Val Leu Pro Gln Arg Asn Ile His Ser 850 855 860 Ser Arg Ile Ala Gly Arg Ser Ala Leu Glu Asp Leu Leu Phe Ser Lys 865 870 875 880 Val Val Thr Ser Gly Leu Gly Thr Val Asp Val Asp Tyr Lys Ser Cys 885 890 895 Thr Lys Gly Leu Ser Ile Ala Asp Leu Ala Cys Ala Gln Tyr Tyr Asn 900 905 910 Gly Ile Met Val Leu Pro Gly Val Ala Asp Ala Glu Arg Met Ala Met 915 920 925 Tyr Thr Gly Ser Leu Ile Gly Gly Met Val Leu Gly Gly Leu Thr Ser 930 935 940 Ala Ala Ala Ile Pro Phe Ser Leu Ala Leu Gln Ala Arg Leu Asn Tyr 945 950 955 960 Val Ala Leu Gln Thr Asp Val Leu Gln Glu Asn Gln Lys Ile Leu Ala 965 970 975 Ala Ser Phe Asn Lys Ala Ile Asn Asn Ile Val Ala Ser Phe Ser Ser 980 985 990 Val Asn Asp Ala Ile Thr Gln Thr Ala Glu Ala Ile His Thr Val Thr 995 1000 1005 Ile Ala Leu Asn Lys Ile Gln Asp Val Val Asn Gln Gln Gly Ser 1010 1015 1020 Ala Leu Asn His Leu Thr Ser Gln Leu Arg His Asn Phe Gln Ala 1025 1030 1035 Ile Ser Asn Ser Ile Gln Ala Ile Tyr Asp Arg Leu Asp Ser Ile 1040 1045 1050 Gln Ala Asp Gln Gln Val Asp Arg Leu Ile Thr Gly Arg Leu Ala 1055 1060 1065 Ala Leu Asn Ala Phe Val Ser Gln Val Leu Asn Lys Tyr Thr Glu 1070 1075 1080 Val Arg Ser Ser Arg Arg Leu Ala Gln Gln Lys Ile Asn Glu Cys 1085 1090 1095 Val Lys Ser Gln Ser Asn Arg Tyr Gly Phe Cys Gly Asn Gly Thr 1100 1105 1110 His Ile Phe Ser Ile Val Asn Ser Ala Pro Asp Gly Leu Leu Phe 1115 1120 1125 Leu His Thr Val Leu Leu Pro Thr Asp Tyr Lys Asn Val Lys Ala 1130 1135 1140 Trp Ser Gly Ile Cys Val Asp Gly Ile Tyr Gly Tyr Val Leu Arg 1145 1150 1155 Gln Pro Asn Leu Val Leu Tyr Ser Asp Asn Gly Val Phe Arg Val 1160 1165 1170 Thr Ser Arg Val Met Phe Gln Pro Arg Leu Pro Val Leu Ser Asp 1175 1180 1185 Phe Val Gln Ile Tyr Asn Cys Asn Val Thr Phe Val Asn Ile Ser 1190 1195 1200 Arg Val Glu Leu His Thr Val Ile Pro Asp Tyr Val Asp Val Asn 1205 1210 1215 Lys Thr Leu Gln Glu Phe Ala Gln Asn Leu Pro Lys Tyr Val Lys 1220 1225 1230 Pro Asn Phe Asp Leu Thr Pro Phe Asn Leu Thr Tyr Leu Asn Leu 1235 1240 1245 Ser Ser Glu Leu Lys Gln Leu Glu Ala Lys Thr Ala Ser Leu Phe 1250 1255 1260 Gln Thr Thr Val Glu Leu Gln Gly Leu Ile Asp Gln Ile Asn Ser 1265 1270 1275 Thr Tyr Val Asp Leu Lys Leu Leu Asn Arg Phe Glu Asn Tyr Ile 1280 1285 1290 Lys Trp Pro Trp Trp Val Trp Leu Ile Ile Ser Val Val Phe Val 1295 1300 1305 Val Leu Leu Ser Leu Leu Val Phe Cys Cys Leu Ser Thr Gly Cys 1310 1315 1320 Cys Gly Cys Cys Asn Cys Leu Thr Ser Ser Met Arg Gly Cys Cys 1325 1330 1335 Asp Cys Gly Ser Thr Lys Leu Pro Tyr Tyr Glu Phe Glu Lys Val 1340 1345 1350 His Val Gln 1355 <![CDATA[<210> 13]]> <![CDATA[<211> 1360]]> <![CDATA[<212> PRT]]> <![CDATA[<213> OC43-CoV 病毒]]> <![CDATA[<400> 13]]> Met Phe Leu Ile Leu Leu Ile Ser Leu Pro Thr Ala Phe Ala Val Ile 1 5 10 15 Gly Asp Leu Asn Cys Thr Leu Asp Pro Arg Leu Lys Gly Ser Phe Asn 20 25 30 Asn Arg Asp Thr Gly Pro Pro Ser Ile Ser Ile Asp Thr Val Asp Val 35 40 45 Thr Asn Gly Leu Gly Thr Tyr Tyr Val Leu Asp Arg Val Tyr Leu Asn 50 55 60 Thr Thr Leu Phe Leu Asn Gly Tyr Tyr Pro Thr Ser Gly Ser Thr Tyr 65 70 75 80 Arg Asn Met Ala Leu Lys Gly Thr Asp Leu Leu Ser Thr Leu Trp Phe 85 90 95 Lys Pro Pro Phe Leu Ser Asp Phe Ile Asn Gly Ile Phe Ala Lys Val 100 105 110 Lys Asn Thr Lys Val Phe Lys Asp Gly Val Met Tyr Ser Glu Phe Pro 115 120 125 Ala Ile Thr Ile Gly Ser Thr Phe Val Asn Thr Ser Tyr Ser Val Val 130 135 140 Val Gln Pro Arg Thr Ile Asn Ser Thr Gln Asp Gly Val Asn Lys Leu 145 150 155 160 Gln Gly Leu Leu Glu Val Ser Val Cys Gln Tyr Asn Met Cys Glu Tyr 165 170 175 Pro His Thr Ile Cys His Pro Asn Leu Gly Asn His Phe Lys Glu Leu 180 185 190 Trp His Tyr Asp Thr Gly Val Val Ser Cys Leu Tyr Lys Arg Asn Phe 195 200 205 Thr Tyr Asp Val Asn Ala Thr Tyr Leu Tyr Phe His Phe Tyr Gln Glu 210 215 220 Gly Gly Thr Phe Tyr Ala Tyr Phe Thr Asp Thr Gly Phe Val Thr Lys 225 230 235 240 Phe Leu Phe Asn Val Tyr Leu Gly Met Ala Leu Ser His Tyr Tyr Val 245 250 255 Met Pro Leu Thr Cys Ile Arg Arg Pro Lys Asp Gly Phe Ser Leu Glu 260 265 270 Tyr Trp Val Thr Pro Leu Thr Pro Arg Gln Tyr Leu Leu Ala Phe Asn 275 280 285 Gln Asp Gly Ile Ile Phe Asn Ala Val Asp Cys Met Ser Asp Phe Met 290 295 300 Ser Glu Ile Lys Cys Lys Thr Gln Ser Ile Ala Pro Pro Thr Gly Val 305 310 315 320 Tyr Glu Leu Asn Gly Tyr Thr Val Gln Pro Val Ala Asp Val Tyr Arg 325 330 335 Arg Lys Pro Asp Leu Pro Asn Cys Asn Ile Glu Ala Trp Leu Asn Asp 340 345 350 Lys Ser Val Pro Ser Pro Leu Asn Trp Glu Arg Lys Thr Phe Ser Asn 355 360 365 Cys Asn Phe Asn Met Ser Ser Leu Met Ser Phe Ile Gln Ala Asp Ser 370 375 380 Phe Thr Cys Asn Asn Ile Asp Ala Ala Lys Ile Tyr Gly Met Cys Phe 385 390 395 400 Ser Ser Ile Thr Ile Asp Lys Phe Ala Ile Pro Asn Arg Arg Lys Val 405 410 415 Asp Leu Gln Leu Gly Asn Leu Gly Tyr Leu Gln Ser Ser Asn Tyr Arg 420 425 430 Ile Asp Thr Thr Ala Thr Ser Cys Gln Leu Tyr Tyr Asn Leu Pro Ala 435 440 445 Ala Asn Val Ser Val Ser Arg Phe Asn Pro Ser Thr Trp Asn Lys Arg 450 455 460 Phe Gly Phe Ile Glu Asp Ser Val Phe Val Pro Gln Pro Thr Gly Val 465 470 475 480 Phe Thr Asn His Ser Val Val Tyr Ala Gln His Cys Phe Lys Ala Pro 485 490 495 Lys Asn Phe Cys Pro Cys Ser Ser Cys Ser Cys Pro Gly Lys Asn Asn 500 505 510 Gly Ile Gly Thr Cys Pro Ala Gly Thr Asn Ser Leu Thr Cys Asp Asn 515 520 525 Leu Cys Thr Leu Asp Pro Ile Thr Leu Lys Ala Pro Asp Thr Tyr Lys 530 535 540 Cys Pro Gln Ser Lys Ser Leu Val Gly Ile Gly Glu His Cys Ser Gly 545 550 555 560 Leu Ala Val Lys Ser Asp Tyr Cys Gly Asn Asn Ser Cys Thr Cys Gln 565 570 575 Pro Gln Ala Phe Leu Gly Trp Ser Ala Asp Ser Cys Leu Gln Gly Asp 580 585 590 Lys Cys Asn Ile Phe Ala Asn Phe Ile Leu His Asp Val Asn Asn Gly 595 600 605 Leu Thr Cys Ser Thr Asp Leu Gln Lys Ala Asn Thr Glu Ile Glu Leu 610 615 620 Gly Val Cys Val Asn Tyr Asp Leu Tyr Gly Ile Ser Gly Gln Gly Ile 625 630 635 640 Phe Val Glu Val Asn Ala Thr Tyr Tyr Asn Ser Trp Gln Asn Leu Leu 645 650 655 Tyr Asp Ser Asn Gly Asn Leu Tyr Gly Phe Arg Asp Tyr Ile Thr Asn 660 665 670 Arg Thr Phe Met Ile His Ser Cys Tyr Ser Gly Arg Val Ser Ala Ala 675 680 685 Tyr His Ala Asn Ser Ser Glu Pro Ala Leu Leu Phe Arg Asn Ile Lys 690 695 700 Cys Asn Tyr Val Phe Asn Asn Ser Leu Thr Arg Gln Leu Gln Pro Ile 705 710 715 720 Asn Tyr Ser Phe Asp Ser Tyr Leu Gly Cys Val Val Asn Ala Tyr Asn 725 730 735 Ser Thr Ala Ile Ser Val Gln Thr Cys Asp Leu Thr Val Gly Ser Gly 740 745 750 Tyr Cys Val Asp Tyr Ser Lys Asn Arg Arg Ser Arg Arg Ala Ile Thr 755 760 765 Thr Gly Tyr Arg Phe Thr Asn Phe Glu Pro Phe Thr Val Asn Ser Val 770 775 780 Asn Asp Ser Leu Glu Pro Val Gly Gly Leu Tyr Glu Ile Gln Ile Pro 785 790 795 800 Ser Glu Phe Thr Ile Gly Asn Met Glu Glu Phe Ile Gln Thr Ser Ser 805 810 815 Pro Lys Val Thr Ile Asp Cys Ala Ala Phe Val Cys Gly Asp Tyr Ala 820 825 830 Ala Cys Lys Leu Gln Leu Val Glu Tyr Gly Ser Phe Cys Asp Asn Ile 835 840 845 Asn Ala Ile Leu Thr Glu Val Asn Glu Leu Leu Asp Thr Thr Gln Leu 850 855 860 Gln Val Ala Asn Ser Leu Met Asn Gly Val Thr Leu Ser Thr Lys Leu 865 870 875 880 Lys Asp Gly Val Asn Phe Asn Val Asp Asp Ile Asn Phe Ser Pro Val 885 890 895 Leu Gly Cys Leu Gly Ser Glu Cys Ser Lys Ala Ser Ser Arg Ser Ala 900 905 910 Ile Glu Asp Leu Leu Phe Asp Lys Val Lys Leu Ser Asp Val Gly Phe 915 920 925 Val Glu Ala Tyr Asn Asn Cys Thr Gly Gly Ala Glu Ile Arg Asp Leu 930 935 940 Ile Cys Val Gln Ser Tyr Lys Gly Ile Lys Val Leu Pro Pro Leu Leu 945 950 955 960 Ser Glu Asn Gln Ile Ser Gly Tyr Thr Leu Ala Ala Thr Ser Ala Ser 965 970 975 Leu Phe Pro Pro Trp Thr Ala Ala Ala Gly Val Pro Phe Tyr Leu Asn 980 985 990 Val Gln Tyr Arg Ile Asn Gly Leu Gly Val Thr Met Asp Val Leu Ser 995 1000 1005 Gln Asn Gln Lys Leu Ile Ala Asn Ala Phe Asn Asn Ala Leu His 1010 1015 1020 Ala Ile Gln Gln Gly Phe Asp Ala Thr Asn Ser Ala Leu Val Lys 1025 1030 1035 Ile Gln Ala Val Val Asn Ala Asn Ala Glu Ala Leu Asn Asn Leu 1040 1045 1050 Leu Gln Gln Leu Ser Asn Arg Phe Gly Ala Ile Ser Ala Ser Leu 1055 1060 1065 Gln Glu Ile Leu Ser Arg Leu Asp Ala Leu Glu Ala Glu Ala Gln 1070 1075 1080 Ile Asp Arg Leu Ile Asn Gly Arg Leu Thr Ala Leu Asn Ala Tyr 1085 1090 1095 Val Ser Gln Gln Leu Ser Asp Ser Thr Leu Val Lys Phe Ser Ala 1100 1105 1110 Ala Gln Ala Met Glu Lys Val Asn Glu Cys Val Lys Ser Gln Ser 1115 1120 1125 Ser Arg Ile Asn Phe Cys Gly Asn Gly Asn His Ile Ile Ser Leu 1130 1135 1140 Val Gln Asn Ala Pro Tyr Gly Leu Tyr Phe Ile His Phe Asn Tyr 1145 1150 1155 Val Pro Thr Lys Tyr Val Thr Ala Lys Val Ser Pro Gly Leu Cys 1160 1165 1170 Ile Ala Gly Asn Arg Gly Ile Ala Pro Lys Ser Gly Tyr Phe Val 1175 1180 1185 Asn Val Asn Asn Thr Trp Met Tyr Thr Gly Ser Gly Tyr Tyr Tyr 1190 1195 1200 Pro Glu Pro Ile Thr Glu Asn Asn Val Val Val Met Ser Thr Cys 1205 1210 1215 Ala Val Asn Tyr Thr Lys Ala Pro Tyr Val Met Leu Asn Thr Ser 1220 1225 1230 Ile Pro Asn Leu Pro Asp Phe Lys Glu Glu Leu Asp Gln Trp Phe 1235 1240 1245 Lys Asn Gln Thr Ser Val Ala Pro Asp Leu Ser Leu Asp Tyr Ile 1250 1255 1260 Asn Val Thr Phe Leu Asp Leu Gln Val Glu Met Asn Arg Leu Gln 1265 1270 1275 Glu Ala Ile Lys Val Leu Asn His Ser Tyr Ile Asn Leu Lys Asp 1280 1285 1290 Ile Gly Thr Tyr Glu Tyr Tyr Val Lys Trp Pro Trp Tyr Val Trp 1295 1300 1305 Leu Leu Ile Cys Leu Ala Gly Val Ala Met Leu Val Leu Leu Phe 1310 1315 1320 Phe Ile Cys Cys Cys Thr Gly Cys Gly Thr Ser Cys Phe Lys Lys 1325 1330 1335 Cys Gly Gly Cys Cys Asp Asp Tyr Thr Gly Tyr Gln Glu Leu Val 1340 1345 1350 Ile Lys Thr Ser His Asp Asp 1355 1360 <![CDATA[<210> 14]]> <![CDATA[<211> 441]]> <![CDATA[<212> PRT]]> <![CDATA[<213> HKU-CoV 病毒]]> <![CDATA[<400> 14]]> Met Ser Tyr Thr Pro Gly His Tyr Ala Gly Ser Arg Ser Ser Ser Gly 1 5 10 15 Asn Arg Ser Gly Ile Leu Lys Lys Thr Ser Trp Ala Asp Gln Ser Glu 20 25 30 Arg Asn Tyr Gln Thr Phe Asn Arg Gly Arg Lys Thr Gln Pro Lys Phe 35 40 45 Thr Val Ser Thr Gln Pro Gln Gly Asn Thr Ile Pro His Tyr Ser Trp 50 55 60 Phe Ser Gly Ile Thr Gln Phe Gln Lys Gly Arg Asp Phe Lys Phe Ser 65 70 75 80 Asp Gly Gln Gly Val Pro Ile Ala Phe Gly Val Pro Pro Ser Glu Ala 85 90 95 Lys Gly Tyr Trp Tyr Arg His Ser Arg Arg Ser Phe Lys Thr Ala Asp 100 105 110 Gly Gln Gln Lys Gln Leu Leu Pro Arg Trp Tyr Phe Tyr Tyr Leu Gly 115 120 125 Thr Gly Pro Tyr Ala Asn Ala Ser Tyr Gly Glu Ser Leu Glu Gly Val 130 135 140 Phe Trp Val Ala Asn His Gln Ala Asp Thr Ser Thr Pro Ser Asp Val 145 150 155 160 Ser Ser Arg Asp Pro Thr Thr Gln Glu Ala Ile Pro Thr Arg Phe Pro 165 170 175 Pro Gly Thr Ile Leu Pro Gln Gly Tyr Tyr Val Glu Gly Ser Gly Arg 180 185 190 Ser Ala Ser Asn Ser Arg Pro Gly Ser Arg Ser Gln Ser Arg Gly Pro 195 200 205 Asn Asn Arg Ser Leu Ser Arg Ser Asn Ser Asn Phe Arg His Ser Asp 210 215 220 Ser Ile Val Lys Pro Asp Met Ala Asp Glu Ile Ala Asn Leu Val Leu 225 230 235 240 Ala Lys Leu Gly Lys Asp Ser Lys Pro Gln Gln Val Thr Lys Gln Asn 245 250 255 Ala Lys Glu Ile Arg His Lys Ile Leu Thr Lys Pro Arg Gln Lys Arg 260 265 270 Thr Pro Asn Lys His Cys Asn Val Gln Gln Cys Phe Gly Lys Arg Gly 275 280 285 Pro Ser Gln Asn Phe Gly Asn Ala Glu Met Leu Lys Leu Gly Thr Asn 290 295 300 Asp Pro Gln Phe Pro Ile Leu Ala Glu Leu Ala Pro Thr Pro Gly Ala 305 310 315 320 Phe Phe Phe Gly Ser Lys Leu Asp Leu Val Lys Arg Asp Ser Glu Ala 325 330 335 Asp Ser Pro Val Lys Asp Val Phe Glu Leu His Tyr Ser Gly Ser Ile 340 345 350 Arg Phe Asp Ser Thr Leu Pro Gly Phe Glu Thr Ile Met Lys Val Leu 355 360 365 Glu Glu Asn Leu Asn Ala Tyr Val Asn Ser Asn Gln Asn Thr Asp Ser 370 375 380 Asp Ser Leu Ser Ser Lys Pro Gln Arg Lys Arg Gly Val Lys Gln Leu 385 390 395 400 Pro Glu Gln Phe Asp Ser Leu Asn Leu Ser Ala Gly Thr Gln His Ile 405 410 415 Ser Asn Asp Phe Thr Pro Glu Asp His Ser Leu Leu Ala Thr Leu Asp 420 425 430 Asp Pro Tyr Val Glu Asp Ser Val Ala 435 440 <![CDATA[<210> 15]]> <![CDATA[<211> 389]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 229E-CoV 病毒]]> <![CDATA[<400> ]]>15 Met Ala Thr Val Lys Trp Ala Asp Ala Ser Glu Pro Gln Arg Gly Arg 1 5 10 15 Gln Gly Arg Ile Pro Tyr Ser Leu Tyr Ser Pro Leu Leu Val Asp Ser 20 25 30 Glu Gln Pro Trp Lys Val Ile Pro Arg Asn Leu Val Pro Ile Asn Lys 35 40 45 Lys Asp Lys Asn Lys Leu Ile Gly Tyr Trp Asn Val Gln Lys Arg Phe 50 55 60 Arg Thr Arg Lys Gly Lys Arg Val Asp Leu Ser Pro Lys Leu His Phe 65 70 75 80 Tyr Tyr Leu Gly Thr Gly Pro His Lys Asp Ala Lys Phe Arg Glu Arg 85 90 95 Val Glu Gly Val Val Trp Val Ala Val Asp Gly Ala Lys Thr Glu Pro 100 105 110 Thr Gly Tyr Gly Val Arg Arg Lys Asn Ser Glu Pro Glu Ile Pro His 115 120 125 Phe Asn Gln Lys Leu Pro Asn Gly Val Thr Val Val Glu Glu Pro Asp 130 135 140 Ser Arg Ala Pro Ser Arg Ser Gln Ser Arg Ser Gln Ser Arg Gly Arg 145 150 155 160 Gly Glu Ser Lys Pro Gln Ser Arg Asn Pro Ser Ser Asp Arg Asn His 165 170 175 Asn Ser Gln Asp Asp Ile Met Lys Ala Val Ala Ala Ala Leu Lys Ser 180 185 190 Leu Gly Phe Asp Lys Pro Gln Glu Lys Asp Lys Lys Ser Ala Lys Thr 195 200 205 Gly Thr Pro Lys Pro Ser Arg Asn Gln Ser Pro Ala Ser Ser Gln Thr 210 215 220 Ser Ala Lys Ser Leu Ala Arg Ser Gln Ser Ser Glu Thr Lys Glu Gln 225 230 235 240 Lys His Glu Met Gln Lys Pro Arg Trp Lys Arg Gln Pro Asn Asp Asp 245 250 255 Val Thr Ser Asn Val Thr Gln Cys Phe Gly Pro Arg Asp Leu Asp His 260 265 270 Asn Phe Gly Ser Ala Gly Val Val Ala Asn Gly Val Lys Ala Lys Gly 275 280 285 Tyr Pro Gln Phe Ala Glu Leu Val Pro Ser Thr Ala Ala Met Leu Phe 290 295 300 Asp Ser His Ile Val Ser Lys Glu Ser Gly Asn Thr Val Val Leu Thr 305 310 315 320 Phe Thr Thr Arg Val Thr Val Pro Lys Asp His Pro His Leu Gly Lys 325 330 335 Phe Leu Glu Glu Leu Asn Ala Phe Thr Arg Glu Met Gln Gln His Pro 340 345 350 Leu Leu Asn Pro Ser Ala Leu Glu Phe Asn Pro Ser Gln Thr Ser Pro 355 360 365 Ala Thr Ala Glu Pro Val Arg Asp Glu Val Ser Ile Glu Thr Asp Ile 370 375 380 Ile Asp Glu Val Asn 385 <![CDATA[<210> 16]]> <![CDATA[<211> 377]]> <![CDATA[<212> PRT]]> <![CDATA[<213> NL63-CoV 病毒]]> <![CDATA[<400> 16]]> Met Ala Ser Val Asn Trp Ala Asp Asp Arg Ala Ala Arg Lys Lys Phe 1 5 10 15 Pro Pro Pro Ser Phe Tyr Met Pro Leu Leu Val Ser Ser Asp Lys Ala 20 25 30 Pro Tyr Arg Val Ile Pro Arg Asn Leu Val Pro Ile Gly Lys Gly Asn 35 40 45 Lys Asp Glu Gln Ile Gly Tyr Trp Asn Val Gln Glu Arg Trp Arg Met 50 55 60 Arg Arg Gly Gln Arg Val Asp Leu Pro Pro Lys Val His Phe Tyr Tyr 65 70 75 80 Leu Gly Thr Gly Pro His Lys Asp Leu Lys Phe Arg Gln Arg Ser Asp 85 90 95 Gly Val Val Trp Val Ala Lys Glu Gly Ala Lys Thr Val Asn Thr Ser 100 105 110 Leu Gly Asn Arg Lys Arg Asn Gln Lys Pro Leu Glu Pro Lys Phe Ser 115 120 125 Ile Ala Leu Pro Pro Glu Leu Ser Val Val Glu Phe Glu Asp Arg Ser 130 135 140 Asn Asn Ser Ser Arg Ala Ser Ser Arg Ser Ser Thr Arg Asn Asn Ser 145 150 155 160 Arg Asp Ser Ser Arg Ser Thr Ser Arg Gln Gln Ser Arg Thr Arg Ser 165 170 175 Asp Ser Asn Gln Ser Ser Ser Asp Leu Val Ala Ala Val Thr Leu Ala 180 185 190 Leu Lys Asn Leu Gly Phe Asp Asn Gln Ser Lys Ser Pro Ser Ser Ser 195 200 205 Gly Thr Ser Thr Pro Lys Lys Pro Asn Lys Pro Leu Ser Gln Pro Arg 210 215 220 Ala Asp Lys Pro Ser Gln Leu Lys Lys Pro Arg Trp Lys Arg Val Pro 225 230 235 240 Thr Arg Glu Glu Asn Val Ile Gln Cys Phe Gly Pro Arg Asp Phe Asn 245 250 255 His Asn Met Gly Asp Ser Asp Leu Val Gln Asn Gly Val Asp Ala Lys 260 265 270 Gly Phe Pro Gln Leu Ala Glu Leu Ile Pro Asn Gln Ala Ala Leu Phe 275 280 285 Phe Asp Ser Glu Val Ser Thr Asp Glu Val Gly Asp Asn Val Gln Ile 290 295 300 Thr Tyr Thr Tyr Lys Met Leu Val Ala Lys Asp Asn Lys Asn Leu Pro 305 310 315 320 Lys Phe Ile Glu Gln Ile Ser Ala Phe Thr Lys Pro Ser Ser Ile Lys 325 330 335 Glu Met Gln Ser Gln Ser Ser His Val Ala Gln Asn Thr Val Leu Asn 340 345 350 Ala Ser Ile Pro Glu Ser Lys Pro Leu Ala Asp Asp Asp Ser Ala Ile 355 360 365 Ile Glu Ile Val Asn Glu Val Leu His 370 375 <![CDATA[<210> 17]]> <![CDATA[<211> 448]]> <![CDATA[<212> PRT]]> <![CDATA[<213> OC43-CoV 病毒]]> <![CDATA[<400> 17]]> Met Ser Phe Thr Pro Gly Lys Gln Ser Ser Ser Arg Ala Ser Ser Gly 1 5 10 15 Asn Arg Ser Gly Asn Gly Ile Leu Lys Trp Ala Asp Gln Ser Asp Gln 20 25 30 Phe Arg Asn Val Gln Thr Arg Gly Arg Arg Ala Gln Pro Lys Gln Thr 35 40 45 Ala Thr Ser Gln Gln Pro Ser Gly Gly Asn Val Val Pro Tyr Tyr Ser 50 55 60 Trp Phe Ser Gly Ile Thr Gln Phe Gln Lys Gly Lys Glu Phe Glu Phe 65 70 75 80 Val Glu Gly Gln Gly Val Pro Ile Ala Pro Gly Val Pro Ala Thr Glu 85 90 95 Ala Lys Gly Tyr Trp Tyr Arg His Asn Arg Arg Ser Phe Lys Thr Ala 100 105 110 Asp Gly Asn Gln Arg Gln Leu Leu Pro Arg Trp Tyr Phe Tyr Tyr Leu 115 120 125 Gly Thr Gly Pro His Ala Lys Asp Gln Tyr Gly Thr Asp Ile Asp Gly 130 135 140 Val Tyr Trp Val Ala Ser Asn Gln Ala Asp Val Asn Thr Pro Ala Asp 145 150 155 160 Ile Val Asp Arg Asp Pro Ser Ser Asp Glu Ala Ile Pro Thr Arg Phe 165 170 175 Pro Pro Gly Thr Val Leu Pro Gln Gly Tyr Tyr Ile Glu Gly Ser Gly 180 185 190 Arg Ser Ala Pro Asn Ser Arg Ser Thr Ser Arg Thr Ser Ser Arg Ala 195 200 205 Ser Ser Ala Gly Ser Arg Ser Arg Ala Asn Ser Gly Asn Arg Thr Pro 210 215 220 Thr Ser Gly Val Thr Pro Asp Met Ala Asp Gln Ile Ala Ser Leu Val 225 230 235 240 Leu Ala Lys Leu Gly Lys Asp Ala Thr Lys Pro Gln Gln Val Thr Lys 245 250 255 His Thr Ala Lys Glu Val Arg Gln Lys Ile Leu Asn Lys Pro Arg Gln 260 265 270 Lys Arg Ser Pro Asn Lys Gln Cys Thr Val Gln Gln Cys Phe Gly Lys 275 280 285 Arg Gly Pro Asn Gln Asn Phe Gly Gly Gly Glu Met Leu Lys Leu Gly 290 295 300 Thr Ser Asp Pro Gln Phe Pro Ile Leu Ala Glu Leu Ala Pro Thr Ala 305 310 315 320 Gly Ala Phe Phe Phe Gly Ser Arg Leu Glu Leu Ala Lys Val Gln Asn 325 330 335 Leu Ser Gly Asn Pro Asp Glu Pro Gln Lys Asp Val Tyr Glu Leu Arg 340 345 350 Tyr Asn Gly Ala Ile Arg Phe Asp Ser Thr Leu Ser Gly Phe Glu Thr 355 360 365 Ile Met Lys Val Leu Asn Glu Asn Leu Asn Ala Tyr Gln Gln Gln Asp 370 375 380 Gly Met Met Asn Met Ser Pro Lys Pro Gln Arg Gln Arg Gly His Lys 385 390 395 400 Asn Gly Gln Gly Glu Asn Asp Asn Ile Ser Val Ala Val Pro Lys Ser 405 410 415 Arg Val Gln Gln Asn Lys Ser Arg Glu Leu Thr Ala Glu Asp Ile Ser 420 425 430 Leu Leu Lys Lys Met Asp Glu Pro Tyr Thr Glu Asp Thr Ser Glu Ile 435 440 445 <![CDATA[<210> 18]]> <![CDATA[<211> 566]]> <![CDATA[<212> PRT]]> <![CDATA[<213> A型流感病毒H1N1亞型]]> <![CDATA[<400> 18]]> Met Lys Ala Ile Leu Val Val Leu Leu Tyr Thr Phe Ala Thr Ala Asn 1 5 10 15 Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr 20 25 30 Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn 35 40 45 Leu Leu Glu Asp Lys His Asn Gly Lys Leu Cys Lys Leu Arg Gly Val 50 55 60 Ala Pro Leu His Leu Gly Lys Cys Asn Ile Ala Gly Trp Ile Leu Gly 65 70 75 80 Asn Pro Glu Cys Glu Ser Leu Ser Thr Ala Ser Ser Trp Ser Tyr Ile 85 90 95 Val Glu Thr Ser Ser Ser Asp Asn Gly Thr Cys Tyr Pro Gly Asp Phe 100 105 110 Ile Asp Tyr Glu Glu Leu Arg Glu Gln Leu Ser Ser Val Ser Ser Phe 115 120 125 Glu Arg Phe Glu Ile Phe Pro Lys Thr Ser Ser Trp Pro Asn His Asp 130 135 140 Ser Asn Lys Gly Val Thr Ala Ala Cys Pro His Ala Gly Ala Lys Ser 145 150 155 160 Phe Tyr Lys Asn Leu Ile Trp Leu Val Lys Lys Gly Asn Ser Tyr Pro 165 170 175 Lys Leu Ser Lys Ser Tyr Ile Asn Asp Lys Gly Lys Glu Val Leu Val 180 185 190 Leu Trp Gly Ile His His Pro Ser Thr Ser Ala Asp Gln Gln Ser Leu 195 200 205 Tyr Gln Asn Ala Asp Ala Tyr Val Phe Val Gly Thr Ser Arg Tyr Ser 210 215 220 Lys Lys Phe Lys Pro Glu Ile Ala Ile Arg Pro Lys Val Arg Asp Gln 225 230 235 240 Glu Gly Arg Met Asn Tyr Tyr Trp Thr Leu Val Glu Pro Gly Asp Lys 245 250 255 Ile Thr Phe Glu Ala Thr Gly Asn Leu Val Val Pro Arg Tyr Ala Phe 260 265 270 Ala Met Glu Arg Asn Ala Gly Ser Gly Ile Ile Ile Ser Asp Thr Pro 275 280 285 Val His Asp Cys Asn Thr Thr Cys Gln Thr Pro Lys Gly Ala Ile Asn 290 295 300 Thr Ser Leu Pro Phe Gln Asn Ile His Pro Ile Thr Ile Gly Lys Cys 305 310 315 320 Pro Lys Tyr Val Lys Ser Thr Lys Leu Arg Leu Ala Thr Gly Leu Arg 325 330 335 Asn Val Pro Ser Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly 340 345 350 Phe Ile Glu Gly Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr 355 360 365 His His Gln Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser 370 375 380 Thr Gln Asn Ala Ile Asp Lys Ile Thr Asn Lys Val Asn Ser Val Ile 385 390 395 400 Glu Lys Met Asn Thr Gln Phe Thr Ala Val Gly Lys Glu Phe Asn His 405 410 415 Leu Glu Lys Arg Ile Glu Asn Leu Asn Lys Lys Val Asp Asp Gly Phe 420 425 430 Leu Asp Ile Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Glu Asn 435 440 445 Glu Arg Thr Leu Asp Tyr His Asp Ser Asn Val Lys Asn Leu Tyr Glu 450 455 460 Lys Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly 465 470 475 480 Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Thr Cys Met Glu Ser Val 485 490 495 Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys Leu 500 505 510 Asn Arg Glu Glu Ile Asp Gly Val Lys Leu Glu Ser Thr Arg Ile Tyr 515 520 525 Gln Ile Leu Ala Ile Tyr Ser Thr Val Ala Ser Ser Leu Val Leu Val 530 535 540 Val Ser Leu Gly Ala Ile Ser Phe Trp Met Cys Ser Asn Gly Ser Leu 545 550 555 560 Gln Cys Arg Ile Cys Ile 565 <![CDATA[<210> 19]]> <![CDATA[<211> 566]]> <![CDATA[<212> PRT]]> <![CDATA[<213> A型流]]>感病毒H3N2亞型 <![CDATA[<400> 19]]> Met Lys Thr Ile Ile Ala Leu Ser Tyr Ile Phe Cys Leu Ala Leu Gly 1 5 10 15 Gln Asp Leu Pro Gly Asn Asp Asn Ser Thr Ala Thr Leu Cys Leu Gly 20 25 30 His His Ala Val Pro Asn Gly Thr Leu Val Lys Thr Ile Thr Asp Asp 35 40 45 Gln Ile Glu Val Thr Asn Ala Thr Glu Leu Val Gln Ser Ser Ser Thr 50 55 60 Gly Lys Ile Cys Asn Asn Pro His Arg Ile Leu Asp Gly Ile Asp Cys 65 70 75 80 Thr Leu Ile Asp Ala Leu Leu Gly Asp Pro His Cys Asp Val Phe Gln 85 90 95 Asn Glu Thr Trp Asp Leu Phe Val Glu Arg Ser Lys Ala Phe Ser Asn 100 105 110 Cys Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Ser Leu Arg Ser Leu Val 115 120 125 Ala Ser Ser Gly Thr Leu Glu Phe Ile Thr Glu Gly Phe Thr Trp Thr 130 135 140 Gly Val Thr Gln Asn Gly Gly Ser Asn Ala Cys Lys Arg Gly Pro Gly 145 150 155 160 Ser Gly Phe Phe Ser Arg Leu Asn Trp Leu Thr Lys Ser Gly Ser Thr 165 170 175 Tyr Pro Val Leu Asn Val Thr Met Pro Asn Asn Asp Asn Phe Asp Lys 180 185 190 Leu Tyr Ile Trp Gly Ile His His Pro Ser Thr Asn Gln Glu Gln Thr 195 200 205 Ser Leu Tyr Val Gln Ala Ser Gly Arg Val Thr Val Ser Thr Arg Arg 210 215 220 Ser Gln Gln Thr Ile Ile Pro Asn Ile Gly Ser Arg Pro Trp Val Arg 225 230 235 240 Gly Leu Ser Ser Arg Ile Ser Ile Tyr Trp Thr Ile Val Lys Pro Gly 245 250 255 Asp Val Leu Val Ile Asn Ser Asn Gly Asn Leu Ile Ala Pro Arg Gly 260 265 270 Tyr Phe Lys Met Arg Thr Gly Lys Ser Ser Ile Met Arg Ser Asp Ala 275 280 285 Pro Ile Asp Thr Cys Ile Ser Glu Cys Ile Thr Pro Asn Gly Ser Ile 290 295 300 Pro Asn Asp Lys Pro Phe Gln Asn Val Asn Lys Ile Thr Tyr Gly Ala 305 310 315 320 Cys Pro Lys Tyr Val Lys Gln Asn Thr Leu Lys Leu Ala Thr Gly Met 325 330 335 Arg Asn Val Pro Glu Lys Gln Thr Arg Gly Leu Phe Gly Ala Ile Ala 340 345 350 Gly Phe Ile Glu Asn Gly Trp Glu Gly Met Ile Asp Gly Trp Tyr Gly 355 360 365 Phe Arg His Gln Asn Ser Glu Gly Thr Gly Gln Ala Ala Asp Leu Lys 370 375 380 Ser Thr Gln Ala Ala Ile Asp Gln Ile Asn Gly Lys Leu Asn Arg Val 385 390 395 400 Ile Glu Lys Thr Asn Glu Lys Phe His Gln Ile Glu Lys Glu Phe Ser 405 410 415 Glu Val Glu Gly Arg Ile Gln Asp Leu Glu Lys Tyr Val Glu Asp Thr 420 425 430 Lys Ile Asp Leu Trp Ser Tyr Asn Ala Glu Leu Leu Val Ala Leu Glu 435 440 445 Asn Gln His Thr Ile Asp Leu Thr Asp Ser Glu Met Asn Lys Leu Phe 450 455 460 Glu Lys Thr Arg Arg Gln Leu Arg Glu Asn Ala Glu Glu Met Gly Asn 465 470 475 480 Gly Cys Phe Lys Ile Tyr His Lys Cys Asp Asn Ala Cys Ile Glu Ser 485 490 495 Ile Arg Asn Gly Thr Tyr Asp His Asp Val Tyr Arg Asp Glu Ala Leu 500 505 510 Asn Asn Arg Phe Gln Ile Lys Gly Val Glu Leu Lys Ser Gly Tyr Lys 515 520 525 Asp Trp Ile Leu Trp Ile Ser Phe Ala Ile Ser Cys Phe Leu Leu Cys 530 535 540 Val Val Leu Leu Gly Phe Ile Met Trp Ala Cys Gln Arg Gly Asn Ile 545 550 555 560 Arg Cys Asn Ile Cys Ile 565 <![CDATA[<210> 20]]> <![CDATA[<211> 585]]> <![CDATA[<212> PRT]]> <![CDATA[<213> B型流感病毒]]> <![CDATA[<400> 20]]> Met Lys Ala Ile Ile Val Leu Leu Met Val Val Thr Ser Asn Ala Asp 1 5 10 15 Arg Ile Cys Thr Gly Ile Thr Ser Ser Asn Ser Pro His Val Val Lys 20 25 30 Thr Ala Thr Gln Gly Glu Val Asn Val Thr Gly Val Ile Pro Leu Thr 35 40 45 Thr Thr Pro Thr Lys Ser His Phe Ala Asn Leu Lys Gly Thr Glu Thr 50 55 60 Arg Gly Lys Leu Cys Pro Lys Cys Leu Asn Cys Thr Asp Leu Asp Val 65 70 75 80 Ala Leu Gly Arg Pro Lys Cys Thr Gly Asn Ile Pro Ser Ala Arg Val 85 90 95 Ser Ile Leu His Glu Val Arg Pro Val Thr Ser Gly Cys Phe Pro Ile 100 105 110 Met His Asp Arg Thr Lys Ile Arg Gln Leu Pro Asn Leu Leu Arg Gly 115 120 125 Tyr Glu His Ile Arg Leu Ser Thr His Asn Val Ile Asn Ala Glu Asn 130 135 140 Ala Pro Gly Gly Pro Tyr Lys Ile Gly Thr Ser Gly Ser Cys Pro Asn 145 150 155 160 Val Thr Asn Gly Asn Gly Phe Phe Ala Thr Met Ala Trp Ala Val Pro 165 170 175 Lys Asn Asp Asn Asn Lys Thr Ala Thr Asn Ser Leu Thr Ile Glu Val 180 185 190 Pro Tyr Ile Cys Thr Glu Gly Glu Asp Gln Ile Thr Val Trp Gly Phe 195 200 205 His Ser Asp Asn Glu Ile Gln Met Ala Lys Leu Tyr Gly Asp Ser Lys 210 215 220 Pro Gln Lys Phe Thr Ser Ser Ala Asn Gly Val Thr Thr His Tyr Val 225 230 235 240 Ser Gln Ile Gly Gly Phe Pro Asn Gln Thr Glu Asp Gly Gly Leu Pro 245 250 255 Gln Ser Gly Arg Ile Val Val Asp Tyr Met Val Gln Lys Ser Gly Lys 260 265 270 Thr Gly Thr Ile Thr Tyr Gln Arg Gly Ile Leu Leu Pro Gln Lys Val 275 280 285 Trp Cys Ala Ser Gly Arg Ser Lys Val Ile Lys Gly Ser Leu Pro Leu 290 295 300 Ile Gly Glu Ala Asp Cys Leu His Glu Lys Tyr Gly Gly Leu Asn Lys 305 310 315 320 Ser Lys Pro Tyr Tyr Thr Gly Glu His Ala Lys Ala Ile Gly Asn Cys 325 330 335 Pro Ile Trp Val Lys Thr Pro Leu Lys Leu Ala Asn Gly Thr Lys Tyr 340 345 350 Arg Pro Pro Ala Lys Leu Leu Lys Glu Arg Gly Phe Phe Gly Ala Ile 355 360 365 Ala Gly Phe Leu Glu Gly Gly Trp Glu Gly Met Ile Ala Gly Trp His 370 375 380 Gly Tyr Thr Ser His Gly Ala His Gly Val Ala Val Ala Ala Asp Leu 385 390 395 400 Lys Ser Thr Gln Glu Ala Ile Asn Lys Ile Thr Lys Asn Leu Asn Ser 405 410 415 Leu Ser Glu Leu Glu Val Lys Asn Leu Gln Arg Leu Ser Gly Ala Met 420 425 430 Asp Glu Leu His Asn Glu Ile Leu Glu Leu Asp Glu Lys Val Asp Asp 435 440 445 Leu Arg Ala Asp Thr Ile Ser Ser Gln Ile Glu Leu Ala Val Leu Leu 450 455 460 Ser Asn Glu Gly Ile Ile Asn Ser Glu Asp Glu His Leu Leu Ala Leu 465 470 475 480 Glu Arg Lys Leu Lys Lys Met Leu Gly Pro Ser Ala Val Glu Ile Gly 485 490 495 Asn Gly Cys Phe Glu Thr Lys His Lys Cys Asn Gln Thr Cys Leu Asp 500 505 510 Arg Ile Ala Ala Gly Thr Phe Asp Ala Gly Glu Phe Ser Leu Pro Thr 515 520 525 Phe Asp Ser Leu Asn Ile Thr Ala Ala Ser Leu Asn Asp Asp Gly Leu 530 535 540 Asp Asn His Thr Ile Leu Leu Tyr Tyr Ser Thr Ala Ala Ser Ser Leu 545 550 555 560 Ala Val Thr Leu Met Ile Ala Ile Phe Val Val Tyr Met Val Ser Arg 565 570 575 Asp Asn Val Ser Cys Ser Ile Cys Leu 580 585
Claims (20)
- 一種蛋白質微陣列,包括: 一載體,其表面包括數個蛋白質陣列區塊;以及 至少一蛋白質,固定於該蛋白質陣列區塊上,其中該至少一蛋白質係來自一病毒且包括一棘蛋白及一核鞘蛋白;該至少一蛋白質包括具有如SEQ ID NO:1所示之胺基酸序列及如SEQ ID NO:4所示之胺基酸序列,且該至少一蛋白質配置用以與一待測樣本中的一第一抗體或一生物製劑產生專一性地結合。
- 如請求項1所述之蛋白質微陣列,其中該載體係一玻璃載體或一尼龍薄膜載體。
- 如請求項1所述之蛋白質微陣列,其中該載體之表面包括一醛基化修飾層或一胺基化修飾層。
- 如請求項1所述之蛋白質微陣列,其中該至少一蛋白質進一步包括一棘蛋白S1結構域、一血球凝集素蛋白或其組合。
- 如請求項1所述之蛋白質微陣列,其中該至少一蛋白質進一步包括選自由如SEQ ID NO:2所示之胺基酸序列、如SEQ ID NO:3所示之胺基酸序列、如SEQ ID NO:5所示之胺基酸序列、如SEQ ID NO:6所示之胺基酸序列、如SEQ ID NO:10所示之胺基酸序列、如SEQ ID NO:11所示之胺基酸序列、如SEQ ID NO:12所示之胺基酸序列、如SEQ ID NO:13所示之胺基酸序列、如SEQ ID NO:14所示之胺基酸序列、如SEQ ID NO:15所示之胺基酸序列、如SEQ ID NO:16所示之胺基酸序列及如SEQ ID NO:17所示之胺基酸序列所組成之群組。
- 如請求項4所述之蛋白質微陣列,其中該至少一蛋白質進一步包括選自由如SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:18、SEQ ID NO:19及SEQ ID NO:20所示之胺基酸序列所組成之群組。
- 如請求項1所述之蛋白質微陣列,其中該病毒係來自選自由新型冠狀病毒、中東呼吸道症候群冠狀病毒、嚴重急性呼吸道症候群冠狀病毒、人類冠狀病毒HKU、人類冠狀病毒229E、人類冠狀病毒NL63、人類冠狀病毒OC43、A型流感病毒H1N1亞型、A型流感病毒H3N2亞型及B型流感病毒所組成之群組。
- 如請求項1所述之蛋白質微陣列,其中該待測樣本係來自一受試者之血液或血清。
- 如請求項1所述之蛋白質微陣列,其中該第一抗體係免疫球蛋白G(IgG)或免疫球蛋白A(IgA)。
- 如請求項1所述之蛋白質微陣列,其中該生物製劑係一單株抗體藥物或一受體阻斷劑。
- 如請求項10所述之蛋白質微陣列,其中該單株抗體藥物係一鼠源性單株抗體或一兔源性單株抗體。
- 如請求項10所述之蛋白質微陣列,其中該單株抗體藥物係抗新型冠狀病毒之棘蛋白的單株抗體、抗新型冠狀病毒之棘蛋白S1結構域的單株抗體或抗新型冠狀病毒之核鞘蛋白的單株抗體。
- 如請求項10所述之蛋白質微陣列,其中該受體阻斷劑係一人類細胞表面之血管收縮素轉化酶2受體阻斷劑。
- 一種病毒感染之檢測方法,包括步驟: 提供如請求項1至13中任一項所述之蛋白質微陣列; 將一非蛋白質之阻斷劑加入至該蛋白質微陣列之蛋白質陣列區塊上,反應5分鐘至10分鐘,以形成一第一蛋白質微陣列; 提供一受試者之血清,並將該血清加入至該第一蛋白質微陣列上,反應50分鐘至70分鐘後進行清洗,以形成一第二蛋白質微陣列; 提供一第二抗體且該第二抗體係經螢光標記或經酵素標記,將該第二抗體加入至該第二蛋白質微陣列上,反應25分鐘至35分鐘後進行清洗,以形成一第三蛋白質微陣列;以及 利用一訊號讀取機讀取自該第三蛋白質微陣列上所產生之光學訊號。
- 一種如請求項1至13中任一項所述之蛋白質微陣列之用途,其中該蛋白質微陣列係用於體外檢測一受試者是否受一病毒感染或用於評估一生物製劑對於阻斷該病毒感染之能力,且該病毒係選自由新型冠狀病毒、中東呼吸道症候群冠狀病毒、嚴重急性呼吸道症候群冠狀病毒、人類冠狀病毒HKU、人類冠狀病毒229E、人類冠狀病毒NL63、人類冠狀病毒OC43、A型流感病毒H1N1亞型、A型流感病毒H3N2亞型及B型流感病毒所組成之群組。
- 如請求項15所述之用途,其中該生物製劑係一單株抗體藥物或一受體阻斷劑。
- 一種體外檢測病毒感染之試劑盒,包括如請求項1至13中任一項所述之蛋白質微陣列以及一第二抗體,其中該第二抗體配置用以與該第一抗體或該生物製劑產生專一性地結合。
- 如請求項17所述之試劑盒,其中該第二抗體係經螢光標記或經酵素標記。
- 如請求項17所述之試劑盒,其中該螢光標記包括花青染料Cy3及花青染料Cy5。
- 如請求項17所述之試劑盒,其中該酵素標記包括生物素及毛地黃素。
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