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 PDF

Info

Publication number
TW202223392A
TW202223392A TW109142296A TW109142296A TW202223392A TW 202223392 A TW202223392 A TW 202223392A TW 109142296 A TW109142296 A TW 109142296A TW 109142296 A TW109142296 A TW 109142296A TW 202223392 A TW202223392 A TW 202223392A
Authority
TW
Taiwan
Prior art keywords
ser
leu
thr
asn
val
Prior art date
Application number
TW109142296A
Other languages
English (en)
Other versions
TWI767434B (zh
Inventor
許觀達
Original Assignee
國立成功大學
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 國立成功大學 filed Critical 國立成功大學
Priority to TW109142296A priority Critical patent/TWI767434B/zh
Priority to US17/140,186 priority patent/US20220170923A1/en
Application granted granted Critical
Publication of TWI767434B publication Critical patent/TWI767434B/zh
Publication of TW202223392A publication Critical patent/TW202223392A/zh

Links

Images

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366Apparatus specially adapted for solid-phase testing
    • G01N33/54373Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56983Viruses
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366Apparatus specially adapted for solid-phase testing
    • G01N33/54386Analytical elements
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854Immunoglobulins
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2469/00Immunoassays for the detection of microorganisms
    • G01N2469/20Detection of antibodies in sample from host which are directed against antigens from microorganisms
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00Screening for compounds of potential therapeutic value
    • G01N2500/04Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Cell Biology (AREA)
  • Pathology (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Virology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Peptides Or Proteins (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

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

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
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℃。
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
表2 控制組樣本
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)

  1. 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。
  2. 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。
  3. 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。
  4. 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。
  5. 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。
  6. 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。
  7. 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。
  8. 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。
  9. 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)。
  10. 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。
  11. 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。
  12. 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。
  13. 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。
  14. 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。
  15. 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。
  16. 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。
  17. 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。
  18. 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。
  19. 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。
  20. 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。
TW109142296A 2020-12-01 2020-12-01 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 TWI767434B (zh)

Priority Applications (2)

Application Number Priority Date Filing Date Title
TW109142296A TWI767434B (zh) 2020-12-01 2020-12-01 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
US17/140,186 US20220170923A1 (en) 2020-12-01 2021-01-04 Protein microarray, detection method thereof and evaluation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
TW109142296A TWI767434B (zh) 2020-12-01 2020-12-01 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

Publications (2)

Publication Number Publication Date
TWI767434B TWI767434B (zh) 2022-06-11
TW202223392A true TW202223392A (zh) 2022-06-16

Family

ID=81752084

Family Applications (1)

Application Number Title Priority Date Filing Date
TW109142296A TWI767434B (zh) 2020-12-01 2020-12-01 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

Country Status (2)

Country Link
US (1) US20220170923A1 (zh)
TW (1) TWI767434B (zh)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1599597B1 (en) * 2003-02-24 2010-08-04 Pritest, Inc. Translucent solid matrix assay device for microarray analysis
WO2007053165A2 (en) * 2005-01-11 2007-05-10 Yale University Virus protein microarray and uses therefor

Also Published As

Publication number Publication date
TWI767434B (zh) 2022-06-11
US20220170923A1 (en) 2022-06-02

Similar Documents

Publication Publication Date Title
US10844442B1 (en) Rapid viral assay
US8540994B2 (en) H5 subtype-specific binding proteins useful for H5 avian influenza diagnosis and surveillance
Wratil et al. Evidence for increased SARS-CoV-2 susceptibility and COVID-19 severity related to pre-existing immunity to seasonal coronaviruses
Liu et al. Comparative research on nucleocapsid and spike glycoprotein as the rapid immunodetection targets of COVID-19 and establishment of immunoassay strips
EP4176265A1 (en) Kits and methods for the enrichment and detection of rna viruses of the coronaviridae family
CN115176162B (zh) 新型冠状病毒抗原及其检测用途
CN112462061A (zh) 检测h1n1、rsv-a和adv3的试剂盒及其应用
Manta et al. Formulation rationale for the development of SARS-COV-2 immunochromatography rapid test kits in India
JP5182753B2 (ja) インフルエンザ罹患リスクの予測方法
TWI767434B (zh) 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
CN108956986B (zh) 新城疫病毒抗体检测试剂盒
Vashisht et al. Exploring the immunodominant epitopes of SARS-CoV-2 nucleocapsid protein as exposure biomarker
US20110027775A1 (en) Detection of influenza virus
JP6357425B2 (ja) 干渉ペプチド及び微生物の検出方法
KR102339334B1 (ko) 인간 메타뉴모바이러스(hMPV)의 항원 M의 특이적 단클론 항체 및 진단 방법에 있어서의 그 용도
Miyagawa et al. Development of a novel rapid immunochromatographic test specific for the H5 influenza virus
TWI838885B (zh) 蛋白質微陣列及其用途與檢測方法
US11066712B1 (en) Rapid viral assay
US20210356466A1 (en) Rapid Viral Assay
JP5490669B2 (ja) 免疫検査試薬、それを用いる検査装置及び検査方法
KR102131844B1 (ko) 인플루엔자와 중동호흡기증후군을 동시에 검출하는 방법 및 키트
CN108693352B (zh) 新城疫病毒抗体检测试剂盒
Tomar et al. Multiple antigenic peptide-based flow through dot-blot assay for simultaneous antibody detection of infectious bronchitis virus and Newcastle disease virus
Pattnaik et al. Serology: A Precise Tool in Diagnosis and Epidemiology of COVID-19
US20130137083A1 (en) Detection of H5N1 Influenza Infection