                         SEQUENCE LISTING

<110>  INSTITUT DE RECHERCHE EN SEMIOCHIMIE ET ETHOLOGIE APPLIQUEE
 
<120>  NUCLEOSIDE ANALOGUES TO INHIBIT THE MAIN PROTEASE OF A 
       CORONAVIRUS

<130>  B14297WO-2

<140>  PCTxxx
<141>  2021-05-20

<150>  EP20305537.1
<151>  2020-05-20

<160>  11    

<170>  PatentIn version 3.5

<210>  1
<211>  306
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Main protease of SARS-CoV-2 (PDB: 6LU7, 2.16 A)

<400>  1

Ser Gly Phe Arg Lys Met Ala Phe Pro Ser Gly Lys Val Glu Gly Cys 
1               5                   10                  15      


Met Val Gln Val Thr Cys Gly Thr Thr Thr Leu Asn Gly Leu Trp Leu 
            20                  25                  30          


Asp Asp Val Val Tyr Cys Pro Arg His Val Ile Cys Thr Ser Glu Asp 
        35                  40                  45              


Met Leu Asn Pro Asn Tyr Glu Asp Leu Leu Ile Arg Lys Ser Asn His 
    50                  55                  60                  


Asn Phe Leu Val Gln Ala Gly Asn Val Gln Leu Arg Val Ile Gly His 
65                  70                  75                  80  


Ser Met Gln Asn Cys Val Leu Lys Leu Lys Val Asp Thr Ala Asn Pro 
                85                  90                  95      


Lys Thr Pro Lys Tyr Lys Phe Val Arg Ile Gln Pro Gly Gln Thr Phe 
            100                 105                 110         


Ser Val Leu Ala Cys Tyr Asn Gly Ser Pro Ser Gly Val Tyr Gln Cys 
        115                 120                 125             


Ala Met Arg Pro Asn Phe Thr Ile Lys Gly Ser Phe Leu Asn Gly Ser 
    130                 135                 140                 


Cys Gly Ser Val Gly Phe Asn Ile Asp Tyr Asp Cys Val Ser Phe Cys 
145                 150                 155                 160 


Tyr Met His His Met Glu Leu Pro Thr Gly Val His Ala Gly Thr Asp 
                165                 170                 175     


Leu Glu Gly Asn Phe Tyr Gly Pro Phe Val Asp Arg Gln Thr Ala Gln 
            180                 185                 190         


Ala Ala Gly Thr Asp Thr Thr Ile Thr Val Asn Val Leu Ala Trp Leu 
        195                 200                 205             


Tyr Ala Ala Val Ile Asn Gly Asp Arg Trp Phe Leu Asn Arg Phe Thr 
    210                 215                 220                 


Thr Thr Leu Asn Asp Phe Asn Leu Val Ala Met Lys Tyr Asn Tyr Glu 
225                 230                 235                 240 


Pro Leu Thr Gln Asp His Val Asp Ile Leu Gly Pro Leu Ser Ala Gln 
                245                 250                 255     


Thr Gly Ile Ala Val Leu Asp Met Cys Ala Ser Leu Lys Glu Leu Leu 
            260                 265                 270         


Gln Asn Gly Met Asn Gly Arg Thr Ile Leu Gly Ser Ala Leu Leu Glu 
        275                 280                 285             


Asp Glu Phe Thr Pro Phe Asp Val Val Arg Gln Cys Ser Gly Val Thr 
    290                 295                 300                 


Phe Gln 
305     


<210>  2
<211>  306
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Main protease of SARS-CoV-1 (PDB: 3V3M)

<400>  2

Ser Gly Phe Arg Lys Met Ala Phe Pro Ser Gly Lys Val Glu Gly Cys 
1               5                   10                  15      


Met Val Gln Val Thr Cys Gly Thr Thr Thr Leu Asn Gly Leu Trp Leu 
            20                  25                  30          


Asp Asp Thr Val Tyr Cys Pro Arg His Val Ile Cys Thr Ala Glu Asp 
        35                  40                  45              


Met Leu Asn Pro Asn Tyr Glu Asp Leu Leu Ile Arg Lys Ser Asn His 
    50                  55                  60                  


Ser Phe Leu Val Gln Ala Gly Asn Val Gln Leu Arg Val Ile Gly His 
65                  70                  75                  80  


Ser Met Gln Asn Cys Leu Leu Arg Leu Lys Val Asp Thr Ser Asn Pro 
                85                  90                  95      


Lys Thr Pro Lys Tyr Lys Phe Val Arg Ile Gln Pro Gly Gln Thr Phe 
            100                 105                 110         


Ser Val Leu Ala Cys Tyr Asn Gly Ser Pro Ser Gly Val Tyr Gln Cys 
        115                 120                 125             


Ala Met Arg Pro Asn His Thr Ile Lys Gly Ser Phe Leu Asn Gly Ser 
    130                 135                 140                 


Cys Gly Ser Val Gly Phe Asn Ile Asp Tyr Asp Cys Val Ser Phe Cys 
145                 150                 155                 160 


Tyr Met His His Met Glu Leu Pro Thr Gly Val His Ala Gly Thr Asp 
                165                 170                 175     


Leu Glu Gly Lys Phe Tyr Gly Pro Phe Val Asp Arg Gln Thr Ala Gln 
            180                 185                 190         


Ala Ala Gly Thr Asp Thr Thr Ile Thr Leu Asn Val Leu Ala Trp Leu 
        195                 200                 205             


Tyr Ala Ala Val Ile Asn Gly Asp Arg Trp Phe Leu Asn Arg Phe Thr 
    210                 215                 220                 


Thr Thr Leu Asn Asp Phe Asn Leu Val Ala Met Lys Tyr Asn Tyr Glu 
225                 230                 235                 240 


Pro Leu Thr Gln Asp His Val Asp Ile Leu Gly Pro Leu Ser Ala Gln 
                245                 250                 255     


Thr Gly Ile Ala Val Leu Asp Met Cys Ala Ala Leu Lys Glu Leu Leu 
            260                 265                 270         


Gln Asn Gly Met Asn Gly Arg Thr Ile Leu Gly Ser Thr Ile Leu Glu 
        275                 280                 285             


Asp Glu Phe Thr Pro Phe Asp Val Val Arg Gln Cys Ser Gly Val Thr 
    290                 295                 300                 


Phe Gln 
305     


<210>  3
<211>  307
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Main protease of FIPV (PDB: 5EU8)

<400>  3

Gly Pro Leu Gly Ser Ser Gly Leu Arg Lys Met Ala Gln Pro Ser Gly 
1               5                   10                  15      


Val Val Glu Pro Cys Ile Val Arg Val Ala Tyr Gly Asn Asn Val Leu 
            20                  25                  30          


Asn Gly Leu Trp Leu Gly Asp Glu Val Ile Cys Pro Arg His Val Ile 
        35                  40                  45              


Ala Ser Asp Thr Ser Arg Val Ile Asn Tyr Glu Asn Glu Leu Ser Ser 
    50                  55                  60                  


Val Arg Leu His Asn Phe Ser Ile Ala Lys Asn Asn Ala Phe Leu Gly 
65                  70                  75                  80  


Val Val Ser Ala Lys Tyr Lys Gly Val Asn Leu Val Leu Lys Val Asn 
                85                  90                  95      


Gln Val Asn Pro Asn Thr Pro Glu His Lys Phe Lys Ser Val Arg Pro 
            100                 105                 110         


Gly Glu Ser Phe Asn Ile Leu Ala Cys Tyr Glu Gly Cys Pro Gly Ser 
        115                 120                 125             


Val Tyr Gly Val Asn Met Arg Ser Gln Gly Thr Ile Lys Gly Ser Phe 
    130                 135                 140                 


Ile Ala Gly Thr Cys Gly Ser Val Gly Tyr Val Leu Glu Asn Gly Thr 
145                 150                 155                 160 


Leu Tyr Phe Val Tyr Met His His Leu Glu Leu Gly Asn Gly Ser His 
                165                 170                 175     


Val Gly Ser Asn Leu Glu Gly Glu Met Tyr Gly Gly Tyr Glu Asp Gln 
            180                 185                 190         


Pro Ser Met Gln Leu Glu Gly Thr Asn Val Met Ser Ser Asp Asn Val 
        195                 200                 205             


Val Ala Phe Leu Tyr Ala Ala Leu Ile Asn Gly Glu Arg Trp Phe Val 
    210                 215                 220                 


Thr Asn Thr Ser Met Thr Leu Glu Ser Tyr Asn Ala Trp Ala Lys Thr 
225                 230                 235                 240 


Asn Ser Phe Thr Glu Ile Val Ser Thr Asp Ala Phe Asn Met Leu Ala 
                245                 250                 255     


Ala Lys Thr Gly Tyr Ser Val Glu Lys Leu Leu Glu Cys Ile Val Arg 
            260                 265                 270         


Leu Asn Lys Gly Phe Gly Gly Arg Thr Ile Leu Ser Tyr Gly Ser Leu 
        275                 280                 285             


Cys Asp Glu Phe Thr Pro Thr Glu Val Ile Arg Gln Met Tyr Gly Val 
    290                 295                 300                 


Asn Leu Gln 
305         


<210>  4
<211>  306
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Main protease of SARS-CoV-2 (PDB: 7BQY, 1.7 A)

<400>  4

Ser Gly Phe Arg Lys Met Ala Phe Pro Ser Gly Lys Val Glu Gly Cys 
1               5                   10                  15      


Met Val Gln Val Thr Cys Gly Thr Thr Thr Leu Asn Gly Leu Trp Leu 
            20                  25                  30          


Asp Asp Val Val Tyr Cys Pro Arg His Val Ile Cys Thr Ser Glu Asp 
        35                  40                  45              


Met Leu Asn Pro Asn Tyr Glu Asp Leu Leu Ile Arg Lys Ser Asn His 
    50                  55                  60                  


Asn Phe Leu Val Gln Ala Gly Asn Val Gln Leu Arg Val Ile Gly His 
65                  70                  75                  80  


Ser Met Gln Asn Cys Val Leu Lys Leu Lys Val Asp Thr Ala Asn Pro 
                85                  90                  95      


Lys Thr Pro Lys Tyr Lys Phe Val Arg Ile Gln Pro Gly Gln Thr Phe 
            100                 105                 110         


Ser Val Leu Ala Cys Tyr Asn Gly Ser Pro Ser Gly Val Tyr Gln Cys 
        115                 120                 125             


Ala Met Arg Pro Asn Phe Thr Ile Lys Gly Ser Phe Leu Asn Gly Ser 
    130                 135                 140                 


Cys Gly Ser Val Gly Phe Asn Ile Asp Tyr Asp Cys Val Ser Phe Cys 
145                 150                 155                 160 


Tyr Met His His Met Glu Leu Pro Thr Gly Val His Ala Gly Thr Asp 
                165                 170                 175     


Leu Glu Gly Asn Phe Tyr Gly Pro Phe Val Asp Arg Gln Thr Ala Gln 
            180                 185                 190         


Ala Ala Gly Thr Asp Thr Thr Ile Thr Val Asn Val Leu Ala Trp Leu 
        195                 200                 205             


Tyr Ala Ala Val Ile Asn Gly Asp Arg Trp Phe Leu Asn Arg Phe Thr 
    210                 215                 220                 


Thr Thr Leu Asn Asp Phe Asn Leu Val Ala Met Lys Tyr Asn Tyr Glu 
225                 230                 235                 240 


Pro Leu Thr Gln Asp His Val Asp Ile Leu Gly Pro Leu Ser Ala Gln 
                245                 250                 255     


Thr Gly Ile Ala Val Leu Asp Met Cys Ala Ser Leu Lys Glu Leu Leu 
            260                 265                 270         


Gln Asn Gly Met Asn Gly Arg Thr Ile Leu Gly Ser Ala Leu Leu Glu 
        275                 280                 285             


Asp Glu Phe Thr Pro Phe Asp Val Val Arg Gln Cys Ser Gly Val Thr 
    290                 295                 300                 


Phe Gln 
305     


<210>  5
<211>  304
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Main protease of porcine TGEV (PDB: 2AMP)

<400>  5

Gly Ser Ser Gly Leu Arg Lys Met Ala Gln Pro Ser Gly Leu Val Glu 
1               5                   10                  15      


Pro Cys Ile Val Arg Val Ser Tyr Gly Asn Asn Val Leu Asn Gly Leu 
            20                  25                  30          


Trp Leu Gly Asp Glu Val Ile Cys Pro Arg His Val Ile Ala Ser Asp 
        35                  40                  45              


Thr Thr Arg Val Ile Asn Tyr Glu Asn Glu Met Ser Ser Val Arg Leu 
    50                  55                  60                  


His Asn Phe Ser Val Ser Lys Asn Asn Val Phe Leu Gly Val Val Ser 
65                  70                  75                  80  


Ala Arg Tyr Lys Gly Val Asn Leu Val Leu Lys Val Asn Gln Val Asn 
                85                  90                  95      


Pro Asn Thr Pro Glu His Lys Phe Lys Ser Ile Lys Ala Gly Glu Ser 
            100                 105                 110         


Phe Asn Ile Leu Ala Cys Tyr Glu Gly Cys Pro Gly Ser Val Tyr Gly 
        115                 120                 125             


Val Asn Met Arg Ser Gln Gly Thr Ile Lys Gly Ser Phe Ile Ala Gly 
    130                 135                 140                 


Thr Cys Gly Ser Val Gly Tyr Val Leu Glu Asn Gly Ile Leu Tyr Phe 
145                 150                 155                 160 


Val Tyr Met His His Leu Glu Leu Gly Asn Gly Ser His Val Gly Ser 
                165                 170                 175     


Asn Phe Glu Gly Glu Met Tyr Gly Gly Tyr Glu Asp Gln Pro Ser Met 
            180                 185                 190         


Gln Leu Glu Gly Thr Asn Val Met Ser Ser Asp Asn Val Val Ala Phe 
        195                 200                 205             


Leu Tyr Ala Ala Leu Ile Asn Gly Glu Arg Trp Phe Val Thr Asn Thr 
    210                 215                 220                 


Ser Met Ser Leu Glu Ser Tyr Asn Thr Trp Ala Lys Thr Asn Ser Phe 
225                 230                 235                 240 


Thr Glu Leu Ser Ser Thr Asp Ala Phe Ser Met Leu Ala Ala Lys Thr 
                245                 250                 255     


Gly Gln Ser Val Glu Lys Leu Leu Asp Ser Ile Val Arg Leu Asn Lys 
            260                 265                 270         


Gly Phe Gly Gly Arg Thr Ile Leu Ser Tyr Gly Ser Leu Cys Asp Glu 
        275                 280                 285             


Phe Thr Pro Thr Glu Val Ile Arg Gln Met Tyr Gly Val Asn Leu Gln 
    290                 295                 300                 


<210>  6
<211>  305
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Main protease of PEDV (PDB: 6L70)

<400>  6

Ala Gly Leu Arg Lys Met Ala Gln Pro Ser Gly Val Val Glu Lys Cys 
1               5                   10                  15      


Ile Val Arg Val Cys Tyr Gly Asn Met Ala Leu Asn Gly Leu Trp Leu 
            20                  25                  30          


Gly Asp Thr Val Met Cys Pro Arg His Val Ile Ala Ser Ser Thr Thr 
        35                  40                  45              


Ser Thr Ile Asp Tyr Asp Tyr Ala Leu Ser Val Leu Arg Leu His Asn 
    50                  55                  60                  


Phe Ser Ile Ser Ser Gly Asn Val Phe Leu Gly Val Val Gly Val Thr 
65                  70                  75                  80  


Met Arg Gly Ala Leu Leu Gln Ile Lys Val Asn Gln Asn Asn Val His 
                85                  90                  95      


Thr Pro Lys Tyr Thr Tyr Arg Thr Val Arg Pro Gly Glu Ser Phe Asn 
            100                 105                 110         


Ile Leu Ala Cys Tyr Asp Gly Ala Ala Ala Gly Val Tyr Gly Val Asn 
        115                 120                 125             


Met Arg Ser Asn Tyr Thr Ile Arg Gly Ser Phe Ile Asn Gly Ala Cys 
    130                 135                 140                 


Gly Ser Pro Gly Tyr Asn Ile Asn Asn Gly Thr Val Glu Phe Cys Tyr 
145                 150                 155                 160 


Leu His Gln Leu Glu Leu Gly Ser Gly Cys His Val Gly Ser Asp Leu 
                165                 170                 175     


Asp Gly Val Met Tyr Gly Gly Tyr Glu Asp Gln Pro Thr Leu Gln Val 
            180                 185                 190         


Glu Gly Ala Ser Ser Leu Phe Thr Glu Asn Val Leu Ala Phe Leu Tyr 
        195                 200                 205             


Ala Ala Leu Ile Asn Gly Ser Thr Trp Trp Leu Ser Ser Ser Arg Ile 
    210                 215                 220                 


Ala Val Asp Arg Phe Asn Glu Trp Ala Val His Asn Gly Met Thr Thr 
225                 230                 235                 240 


Val Val Asn Thr Asp Cys Phe Ser Ile Leu Ala Ala Lys Thr Gly Val 
                245                 250                 255     


Asp Val Gln Arg Leu Leu Ala Ser Ile Gln Ser Leu His Lys Asn Phe 
            260                 265                 270         


Gly Gly Lys Gln Ile Leu Gly Tyr Thr Ser Leu Thr Asp Glu Phe Thr 
        275                 280                 285             


Thr Gly Glu Val Ile Arg Gln Met Tyr Gly Val His His His His His 
    290                 295                 300                 


His 
305 


<210>  7
<211>  123
<212>  PRT
<213>  Artificial sequence

<220>
<223>  BCoV-HE (PDB: 3CL5)

<400>  7

Phe Asp Asn Pro Pro Thr Asn Val Val Ser His Leu Asn Gly Asp Trp 
1               5                   10                  15      


Phe Leu Phe Gly Asp Ala Arg Ser Asp Cys Asn His Val Val Asn Thr 
            20                  25                  30          


Asn Pro Arg Asn Tyr Ser Tyr Met Asp Leu Asn Pro Ala Leu Cys Asp 
        35                  40                  45              


Ser Gly Lys Ile Ser Ser Lys Ala Gly Asn Ser Ile Phe Arg Ser Phe 
    50                  55                  60                  


His Phe Thr Asp Phe Tyr Asn Tyr Thr Gly Glu Gly Gln Gln Ile Ile 
65                  70                  75                  80  


Phe Tyr Glu Gly Val Asn Phe Thr Pro Tyr His Ala Phe Lys Cys Thr 
                85                  90                  95      


Thr Ser Gly Ser Asn Asp Ile Trp Met Gln Asn Lys Gly Leu Phe Tyr 
            100                 105                 110         


Thr Gln Val Tyr Lys Asn Met Ala Val Tyr Arg 
        115                 120             


<210>  8
<211>  932
<212>  PRT
<213>  Artificial sequence

<220>
<223>  6M71 RNA dependent RNA polymerase of SARS-CoV-2

<400>  8

Ser Ala Asp Ala Gln Ser Phe Leu Asn Arg Val Cys Gly Val Ser Ala 
1               5                   10                  15      


Ala Arg Leu Thr Pro Cys Gly Thr Gly Thr Ser Thr Asp Val Val Tyr 
            20                  25                  30          


Arg Ala Phe Asp Ile Tyr Asn Asp Lys Val Ala Gly Phe Ala Lys Phe 
        35                  40                  45              


Leu Lys Thr Asn Cys Cys Arg Phe Gln Glu Lys Asp Glu Asp Asp Asn 
    50                  55                  60                  


Leu Ile Asp Ser Tyr Phe Val Val Lys Arg His Thr Phe Ser Asn Tyr 
65                  70                  75                  80  


Gln His Glu Glu Thr Ile Tyr Asn Leu Leu Lys Asp Cys Pro Ala Val 
                85                  90                  95      


Ala Lys His Asp Phe Phe Lys Phe Arg Ile Asp Gly Asp Met Val Pro 
            100                 105                 110         


His Ile Ser Arg Gln Arg Leu Thr Lys Tyr Thr Met Ala Asp Leu Val 
        115                 120                 125             


Tyr Ala Leu Arg His Phe Asp Glu Gly Asn Cys Asp Thr Leu Lys Glu 
    130                 135                 140                 


Ile Leu Val Thr Tyr Asn Cys Cys Asp Asp Asp Tyr Phe Asn Lys Lys 
145                 150                 155                 160 


Asp Trp Tyr Asp Phe Val Glu Asn Pro Asp Ile Leu Arg Val Tyr Ala 
                165                 170                 175     


Asn Leu Gly Glu Arg Val Arg Gln Ala Leu Leu Lys Thr Val Gln Phe 
            180                 185                 190         


Cys Asp Ala Met Arg Asn Ala Gly Ile Val Gly Val Leu Thr Leu Asp 
        195                 200                 205             


Asn Gln Asp Leu Asn Gly Asn Trp Tyr Asp Phe Gly Asp Phe Ile Gln 
    210                 215                 220                 


Thr Thr Pro Gly Ser Gly Val Pro Val Val Asp Ser Tyr Tyr Ser Leu 
225                 230                 235                 240 


Leu Met Pro Ile Leu Thr Leu Thr Arg Ala Leu Thr Ala Glu Ser His 
                245                 250                 255     


Val Asp Thr Asp Leu Thr Lys Pro Tyr Ile Lys Trp Asp Leu Leu Lys 
            260                 265                 270         


Tyr Asp Phe Thr Glu Glu Arg Leu Lys Leu Phe Asp Arg Tyr Phe Lys 
        275                 280                 285             


Tyr Trp Asp Gln Thr Tyr His Pro Asn Cys Val Asn Cys Leu Asp Asp 
    290                 295                 300                 


Arg Cys Ile Leu His Cys Ala Asn Phe Asn Val Leu Phe Ser Thr Val 
305                 310                 315                 320 


Phe Pro Pro Thr Ser Phe Gly Pro Leu Val Arg Lys Ile Phe Val Asp 
                325                 330                 335     


Gly Val Pro Phe Val Val Ser Thr Gly Tyr His Phe Arg Glu Leu Gly 
            340                 345                 350         


Val Val His Asn Gln Asp Val Asn Leu His Ser Ser Arg Leu Ser Phe 
        355                 360                 365             


Lys Glu Leu Leu Val Tyr Ala Ala Asp Pro Ala Met His Ala Ala Ser 
    370                 375                 380                 


Gly Asn Leu Leu Leu Asp Lys Arg Thr Thr Cys Phe Ser Val Ala Ala 
385                 390                 395                 400 


Leu Thr Asn Asn Val Ala Phe Gln Thr Val Lys Pro Gly Asn Phe Asn 
                405                 410                 415     


Lys Asp Phe Tyr Asp Phe Ala Val Ser Lys Gly Phe Phe Lys Glu Gly 
            420                 425                 430         


Ser Ser Val Glu Leu Lys His Phe Phe Phe Ala Gln Asp Gly Asn Ala 
        435                 440                 445             


Ala Ile Ser Asp Tyr Asp Tyr Tyr Arg Tyr Asn Leu Pro Thr Met Cys 
    450                 455                 460                 


Asp Ile Arg Gln Leu Leu Phe Val Val Glu Val Val Asp Lys Tyr Phe 
465                 470                 475                 480 


Asp Cys Tyr Asp Gly Gly Cys Ile Asn Ala Asn Gln Val Ile Val Asn 
                485                 490                 495     


Asn Leu Asp Lys Ser Ala Gly Phe Pro Phe Asn Lys Trp Gly Lys Ala 
            500                 505                 510         


Arg Leu Tyr Tyr Asp Ser Met Ser Tyr Glu Asp Gln Asp Ala Leu Phe 
        515                 520                 525             


Ala Tyr Thr Lys Arg Asn Val Ile Pro Thr Ile Thr Gln Met Asn Leu 
    530                 535                 540                 


Lys Tyr Ala Ile Ser Ala Lys Asn Arg Ala Arg Thr Val Ala Gly Val 
545                 550                 555                 560 


Ser Ile Cys Ser Thr Met Thr Asn Arg Gln Phe His Gln Lys Leu Leu 
                565                 570                 575     


Lys Ser Ile Ala Ala Thr Arg Gly Ala Thr Val Val Ile Gly Thr Ser 
            580                 585                 590         


Lys Phe Tyr Gly Gly Trp His Asn Met Leu Lys Thr Val Tyr Ser Asp 
        595                 600                 605             


Val Glu Asn Pro His Leu Met Gly Trp Asp Tyr Pro Lys Cys Asp Arg 
    610                 615                 620                 


Ala Met Pro Asn Met Leu Arg Ile Met Ala Ser Leu Val Leu Ala Arg 
625                 630                 635                 640 


Lys His Thr Thr Cys Cys Ser Leu Ser His Arg Phe Tyr Arg Leu Ala 
                645                 650                 655     


Asn Glu Cys Ala Gln Val Leu Ser Glu Met Val Met Cys Gly Gly Ser 
            660                 665                 670         


Leu Tyr Val Lys Pro Gly Gly Thr Ser Ser Gly Asp Ala Thr Thr Ala 
        675                 680                 685             


Tyr Ala Asn Ser Val Phe Asn Ile Cys Gln Ala Val Thr Ala Asn Val 
    690                 695                 700                 


Asn Ala Leu Leu Ser Thr Asp Gly Asn Lys Ile Ala Asp Lys Tyr Val 
705                 710                 715                 720 


Arg Asn Leu Gln His Arg Leu Tyr Glu Cys Leu Tyr Arg Asn Arg Asp 
                725                 730                 735     


Val Asp Thr Asp Phe Val Asn Glu Phe Tyr Ala Tyr Leu Arg Lys His 
            740                 745                 750         


Phe Ser Met Met Ile Leu Ser Asp Asp Ala Val Val Cys Phe Asn Ser 
        755                 760                 765             


Thr Tyr Ala Ser Gln Gly Leu Val Ala Ser Ile Lys Asn Phe Lys Ser 
    770                 775                 780                 


Val Leu Tyr Tyr Gln Asn Asn Val Phe Met Ser Glu Ala Lys Cys Trp 
785                 790                 795                 800 


Thr Glu Thr Asp Leu Thr Lys Gly Pro His Glu Phe Cys Ser Gln His 
                805                 810                 815     


Thr Met Leu Val Lys Gln Gly Asp Asp Tyr Val Tyr Leu Pro Tyr Pro 
            820                 825                 830         


Asp Pro Ser Arg Ile Leu Gly Ala Gly Cys Phe Val Asp Asp Ile Val 
        835                 840                 845             


Lys Thr Asp Gly Thr Leu Met Ile Glu Arg Phe Val Ser Leu Ala Ile 
    850                 855                 860                 


Asp Ala Tyr Pro Leu Thr Lys His Pro Asn Gln Glu Tyr Ala Asp Val 
865                 870                 875                 880 


Phe His Leu Tyr Leu Gln Tyr Ile Arg Lys Leu His Asp Glu Leu Thr 
                885                 890                 895     


Gly His Met Leu Asp Met Tyr Ser Val Met Leu Thr Asn Asp Asn Thr 
            900                 905                 910         


Ser Arg Tyr Trp Glu Pro Glu Phe Tyr Glu Ala Met Tyr Thr Pro His 
        915                 920                 925             


Thr Val Leu Gln 
    930         


<210>  9
<211>  951
<212>  PRT
<213>  Artificial sequence

<220>
<223>  7BV1 RNA dependent RNA polymerase of SARS-CoV-2

<400>  9

Met Ser Ala Asp Ala Gln Ser Phe Leu Asn Arg Val Cys Gly Val Ser 
1               5                   10                  15      


Ala Ala Arg Leu Thr Pro Cys Gly Thr Gly Thr Ser Thr Asp Val Val 
            20                  25                  30          


Tyr Arg Ala Phe Asp Ile Tyr Asn Asp Lys Val Ala Gly Phe Ala Lys 
        35                  40                  45              


Phe Leu Lys Thr Asn Cys Cys Arg Phe Gln Glu Lys Asp Glu Asp Asp 
    50                  55                  60                  


Asn Leu Ile Asp Ser Tyr Phe Val Val Lys Arg His Thr Phe Ser Asn 
65                  70                  75                  80  


Tyr Gln His Glu Glu Thr Ile Tyr Asn Leu Leu Lys Asp Cys Pro Ala 
                85                  90                  95      


Val Ala Lys His Asp Phe Phe Lys Phe Arg Ile Asp Gly Asp Met Val 
            100                 105                 110         


Pro His Ile Ser Arg Gln Arg Leu Thr Lys Tyr Thr Met Ala Asp Leu 
        115                 120                 125             


Val Tyr Ala Leu Arg His Phe Asp Glu Gly Asn Cys Asp Thr Leu Lys 
    130                 135                 140                 


Glu Ile Leu Val Thr Tyr Asn Cys Cys Asp Asp Asp Tyr Phe Asn Lys 
145                 150                 155                 160 


Lys Asp Trp Tyr Asp Phe Val Glu Asn Pro Asp Ile Leu Arg Val Tyr 
                165                 170                 175     


Ala Asn Leu Gly Glu Arg Val Arg Gln Ala Leu Leu Lys Thr Val Gln 
            180                 185                 190         


Phe Cys Asp Ala Met Arg Asn Ala Gly Ile Val Gly Val Leu Thr Leu 
        195                 200                 205             


Asp Asn Gln Asp Leu Asn Gly Asn Trp Tyr Asp Phe Gly Asp Phe Ile 
    210                 215                 220                 


Gln Thr Thr Pro Gly Ser Gly Val Pro Val Val Asp Ser Tyr Tyr Ser 
225                 230                 235                 240 


Leu Leu Met Pro Ile Leu Thr Leu Thr Arg Ala Leu Thr Ala Glu Ser 
                245                 250                 255     


His Val Asp Thr Asp Leu Thr Lys Pro Tyr Ile Lys Trp Asp Leu Leu 
            260                 265                 270         


Lys Tyr Asp Phe Thr Glu Glu Arg Leu Lys Leu Phe Asp Arg Tyr Phe 
        275                 280                 285             


Lys Tyr Trp Asp Gln Thr Tyr His Pro Asn Cys Val Asn Cys Leu Asp 
    290                 295                 300                 


Asp Arg Cys Ile Leu His Cys Ala Asn Phe Asn Val Leu Phe Ser Thr 
305                 310                 315                 320 


Val Phe Pro Pro Thr Ser Phe Gly Pro Leu Val Arg Lys Ile Phe Val 
                325                 330                 335     


Asp Gly Val Pro Phe Val Val Ser Thr Gly Tyr His Phe Arg Glu Leu 
            340                 345                 350         


Gly Val Val His Asn Gln Asp Val Asn Leu His Ser Ser Arg Leu Ser 
        355                 360                 365             


Phe Lys Glu Leu Leu Val Tyr Ala Ala Asp Pro Ala Met His Ala Ala 
    370                 375                 380                 


Ser Gly Asn Leu Leu Leu Asp Lys Arg Thr Thr Cys Phe Ser Val Ala 
385                 390                 395                 400 


Ala Leu Thr Asn Asn Val Ala Phe Gln Thr Val Lys Pro Gly Asn Phe 
                405                 410                 415     


Asn Lys Asp Phe Tyr Asp Phe Ala Val Ser Lys Gly Phe Phe Lys Glu 
            420                 425                 430         


Gly Ser Ser Val Glu Leu Lys His Phe Phe Phe Ala Gln Asp Gly Asn 
        435                 440                 445             


Ala Ala Ile Ser Asp Tyr Asp Tyr Tyr Arg Tyr Asn Leu Pro Thr Met 
    450                 455                 460                 


Cys Asp Ile Arg Gln Leu Leu Phe Val Val Glu Val Val Asp Lys Tyr 
465                 470                 475                 480 


Phe Asp Cys Tyr Asp Gly Gly Cys Ile Asn Ala Asn Gln Val Ile Val 
                485                 490                 495     


Asn Asn Leu Asp Lys Ser Ala Gly Phe Pro Phe Asn Lys Trp Gly Lys 
            500                 505                 510         


Ala Arg Leu Tyr Tyr Asp Ser Met Ser Tyr Glu Asp Gln Asp Ala Leu 
        515                 520                 525             


Phe Ala Tyr Thr Lys Arg Asn Val Ile Pro Thr Ile Thr Gln Met Asn 
    530                 535                 540                 


Leu Lys Tyr Ala Ile Ser Ala Lys Asn Arg Ala Arg Thr Val Ala Gly 
545                 550                 555                 560 


Val Ser Ile Cys Ser Thr Met Thr Asn Arg Gln Phe His Gln Lys Leu 
                565                 570                 575     


Leu Lys Ser Ile Ala Ala Thr Arg Gly Ala Thr Val Val Ile Gly Thr 
            580                 585                 590         


Ser Lys Phe Tyr Gly Gly Trp His Asn Met Leu Lys Thr Val Tyr Ser 
        595                 600                 605             


Asp Val Glu Asn Pro His Leu Met Gly Trp Asp Tyr Pro Lys Cys Asp 
    610                 615                 620                 


Arg Ala Met Pro Asn Met Leu Arg Ile Met Ala Ser Leu Val Leu Ala 
625                 630                 635                 640 


Arg Lys His Thr Thr Cys Cys Ser Leu Ser His Arg Phe Tyr Arg Leu 
                645                 650                 655     


Ala Asn Glu Cys Ala Gln Val Leu Ser Glu Met Val Met Cys Gly Gly 
            660                 665                 670         


Ser Leu Tyr Val Lys Pro Gly Gly Thr Ser Ser Gly Asp Ala Thr Thr 
        675                 680                 685             


Ala Tyr Ala Asn Ser Val Phe Asn Ile Cys Gln Ala Val Thr Ala Asn 
    690                 695                 700                 


Val Asn Ala Leu Leu Ser Thr Asp Gly Asn Lys Ile Ala Asp Lys Tyr 
705                 710                 715                 720 


Val Arg Asn Leu Gln His Arg Leu Tyr Glu Cys Leu Tyr Arg Asn Arg 
                725                 730                 735     


Asp Val Asp Thr Asp Phe Val Asn Glu Phe Tyr Ala Tyr Leu Arg Lys 
            740                 745                 750         


His Phe Ser Met Met Ile Leu Ser Asp Asp Ala Val Val Cys Phe Asn 
        755                 760                 765             


Ser Thr Tyr Ala Ser Gln Gly Leu Val Ala Ser Ile Lys Asn Phe Lys 
    770                 775                 780                 


Ser Val Leu Tyr Tyr Gln Asn Asn Val Phe Met Ser Glu Ala Lys Cys 
785                 790                 795                 800 


Trp Thr Glu Thr Asp Leu Thr Lys Gly Pro His Glu Phe Cys Ser Gln 
                805                 810                 815     


His Thr Met Leu Val Lys Gln Gly Asp Asp Tyr Val Tyr Leu Pro Tyr 
            820                 825                 830         


Pro Asp Pro Ser Arg Ile Leu Gly Ala Gly Cys Phe Val Asp Asp Ile 
        835                 840                 845             


Val Lys Thr Asp Gly Thr Leu Met Ile Glu Arg Phe Val Ser Leu Ala 
    850                 855                 860                 


Ile Asp Ala Tyr Pro Leu Thr Lys His Pro Asn Gln Glu Tyr Ala Asp 
865                 870                 875                 880 


Val Phe His Leu Tyr Leu Gln Tyr Ile Arg Lys Leu His Asp Glu Leu 
                885                 890                 895     


Thr Gly His Met Leu Asp Met Tyr Ser Val Met Leu Thr Asn Asp Asn 
            900                 905                 910         


Thr Ser Arg Tyr Trp Glu Pro Glu Phe Tyr Glu Ala Met Tyr Thr Pro 
        915                 920                 925             


His Thr Val Leu Gln Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly His 
    930                 935                 940                 


His His His His His His His 
945                 950     


<210>  10
<211>  951
<212>  PRT
<213>  Artificial sequence

<220>
<223>  7BV2 RNA dependent RNA polymerase of SARS-CoV-2

<400>  10

Met Ser Ala Asp Ala Gln Ser Phe Leu Asn Arg Val Cys Gly Val Ser 
1               5                   10                  15      


Ala Ala Arg Leu Thr Pro Cys Gly Thr Gly Thr Ser Thr Asp Val Val 
            20                  25                  30          


Tyr Arg Ala Phe Asp Ile Tyr Asn Asp Lys Val Ala Gly Phe Ala Lys 
        35                  40                  45              


Phe Leu Lys Thr Asn Cys Cys Arg Phe Gln Glu Lys Asp Glu Asp Asp 
    50                  55                  60                  


Asn Leu Ile Asp Ser Tyr Phe Val Val Lys Arg His Thr Phe Ser Asn 
65                  70                  75                  80  


Tyr Gln His Glu Glu Thr Ile Tyr Asn Leu Leu Lys Asp Cys Pro Ala 
                85                  90                  95      


Val Ala Lys His Asp Phe Phe Lys Phe Arg Ile Asp Gly Asp Met Val 
            100                 105                 110         


Pro His Ile Ser Arg Gln Arg Leu Thr Lys Tyr Thr Met Ala Asp Leu 
        115                 120                 125             


Val Tyr Ala Leu Arg His Phe Asp Glu Gly Asn Cys Asp Thr Leu Lys 
    130                 135                 140                 


Glu Ile Leu Val Thr Tyr Asn Cys Cys Asp Asp Asp Tyr Phe Asn Lys 
145                 150                 155                 160 


Lys Asp Trp Tyr Asp Phe Val Glu Asn Pro Asp Ile Leu Arg Val Tyr 
                165                 170                 175     


Ala Asn Leu Gly Glu Arg Val Arg Gln Ala Leu Leu Lys Thr Val Gln 
            180                 185                 190         


Phe Cys Asp Ala Met Arg Asn Ala Gly Ile Val Gly Val Leu Thr Leu 
        195                 200                 205             


Asp Asn Gln Asp Leu Asn Gly Asn Trp Tyr Asp Phe Gly Asp Phe Ile 
    210                 215                 220                 


Gln Thr Thr Pro Gly Ser Gly Val Pro Val Val Asp Ser Tyr Tyr Ser 
225                 230                 235                 240 


Leu Leu Met Pro Ile Leu Thr Leu Thr Arg Ala Leu Thr Ala Glu Ser 
                245                 250                 255     


His Val Asp Thr Asp Leu Thr Lys Pro Tyr Ile Lys Trp Asp Leu Leu 
            260                 265                 270         


Lys Tyr Asp Phe Thr Glu Glu Arg Leu Lys Leu Phe Asp Arg Tyr Phe 
        275                 280                 285             


Lys Tyr Trp Asp Gln Thr Tyr His Pro Asn Cys Val Asn Cys Leu Asp 
    290                 295                 300                 


Asp Arg Cys Ile Leu His Cys Ala Asn Phe Asn Val Leu Phe Ser Thr 
305                 310                 315                 320 


Val Phe Pro Pro Thr Ser Phe Gly Pro Leu Val Arg Lys Ile Phe Val 
                325                 330                 335     


Asp Gly Val Pro Phe Val Val Ser Thr Gly Tyr His Phe Arg Glu Leu 
            340                 345                 350         


Gly Val Val His Asn Gln Asp Val Asn Leu His Ser Ser Arg Leu Ser 
        355                 360                 365             


Phe Lys Glu Leu Leu Val Tyr Ala Ala Asp Pro Ala Met His Ala Ala 
    370                 375                 380                 


Ser Gly Asn Leu Leu Leu Asp Lys Arg Thr Thr Cys Phe Ser Val Ala 
385                 390                 395                 400 


Ala Leu Thr Asn Asn Val Ala Phe Gln Thr Val Lys Pro Gly Asn Phe 
                405                 410                 415     


Asn Lys Asp Phe Tyr Asp Phe Ala Val Ser Lys Gly Phe Phe Lys Glu 
            420                 425                 430         


Gly Ser Ser Val Glu Leu Lys His Phe Phe Phe Ala Gln Asp Gly Asn 
        435                 440                 445             


Ala Ala Ile Ser Asp Tyr Asp Tyr Tyr Arg Tyr Asn Leu Pro Thr Met 
    450                 455                 460                 


Cys Asp Ile Arg Gln Leu Leu Phe Val Val Glu Val Val Asp Lys Tyr 
465                 470                 475                 480 


Phe Asp Cys Tyr Asp Gly Gly Cys Ile Asn Ala Asn Gln Val Ile Val 
                485                 490                 495     


Asn Asn Leu Asp Lys Ser Ala Gly Phe Pro Phe Asn Lys Trp Gly Lys 
            500                 505                 510         


Ala Arg Leu Tyr Tyr Asp Ser Met Ser Tyr Glu Asp Gln Asp Ala Leu 
        515                 520                 525             


Phe Ala Tyr Thr Lys Arg Asn Val Ile Pro Thr Ile Thr Gln Met Asn 
    530                 535                 540                 


Leu Lys Tyr Ala Ile Ser Ala Lys Asn Arg Ala Arg Thr Val Ala Gly 
545                 550                 555                 560 


Val Ser Ile Cys Ser Thr Met Thr Asn Arg Gln Phe His Gln Lys Leu 
                565                 570                 575     


Leu Lys Ser Ile Ala Ala Thr Arg Gly Ala Thr Val Val Ile Gly Thr 
            580                 585                 590         


Ser Lys Phe Tyr Gly Gly Trp His Asn Met Leu Lys Thr Val Tyr Ser 
        595                 600                 605             


Asp Val Glu Asn Pro His Leu Met Gly Trp Asp Tyr Pro Lys Cys Asp 
    610                 615                 620                 


Arg Ala Met Pro Asn Met Leu Arg Ile Met Ala Ser Leu Val Leu Ala 
625                 630                 635                 640 


Arg Lys His Thr Thr Cys Cys Ser Leu Ser His Arg Phe Tyr Arg Leu 
                645                 650                 655     


Ala Asn Glu Cys Ala Gln Val Leu Ser Glu Met Val Met Cys Gly Gly 
            660                 665                 670         


Ser Leu Tyr Val Lys Pro Gly Gly Thr Ser Ser Gly Asp Ala Thr Thr 
        675                 680                 685             


Ala Tyr Ala Asn Ser Val Phe Asn Ile Cys Gln Ala Val Thr Ala Asn 
    690                 695                 700                 


Val Asn Ala Leu Leu Ser Thr Asp Gly Asn Lys Ile Ala Asp Lys Tyr 
705                 710                 715                 720 


Val Arg Asn Leu Gln His Arg Leu Tyr Glu Cys Leu Tyr Arg Asn Arg 
                725                 730                 735     


Asp Val Asp Thr Asp Phe Val Asn Glu Phe Tyr Ala Tyr Leu Arg Lys 
            740                 745                 750         


His Phe Ser Met Met Ile Leu Ser Asp Asp Ala Val Val Cys Phe Asn 
        755                 760                 765             


Ser Thr Tyr Ala Ser Gln Gly Leu Val Ala Ser Ile Lys Asn Phe Lys 
    770                 775                 780                 


Ser Val Leu Tyr Tyr Gln Asn Asn Val Phe Met Ser Glu Ala Lys Cys 
785                 790                 795                 800 


Trp Thr Glu Thr Asp Leu Thr Lys Gly Pro His Glu Phe Cys Ser Gln 
                805                 810                 815     


His Thr Met Leu Val Lys Gln Gly Asp Asp Tyr Val Tyr Leu Pro Tyr 
            820                 825                 830         


Pro Asp Pro Ser Arg Ile Leu Gly Ala Gly Cys Phe Val Asp Asp Ile 
        835                 840                 845             


Val Lys Thr Asp Gly Thr Leu Met Ile Glu Arg Phe Val Ser Leu Ala 
    850                 855                 860                 


Ile Asp Ala Tyr Pro Leu Thr Lys His Pro Asn Gln Glu Tyr Ala Asp 
865                 870                 875                 880 


Val Phe His Leu Tyr Leu Gln Tyr Ile Arg Lys Leu His Asp Glu Leu 
                885                 890                 895     


Thr Gly His Met Leu Asp Met Tyr Ser Val Met Leu Thr Asn Asp Asn 
            900                 905                 910         


Thr Ser Arg Tyr Trp Glu Pro Glu Phe Tyr Glu Ala Met Tyr Thr Pro 
        915                 920                 925             


His Thr Val Leu Gln Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly His 
    930                 935                 940                 


His His His His His His His 
945                 950     


<210>  11
<211>  923
<212>  PRT
<213>  Artificial sequence

<220>
<223>  7BW4 RNA dependent RNA polymerase of SARS-CoV-2

<400>  11

Arg Val Cys Gly Val Ser Ala Ala Arg Leu Thr Pro Cys Gly Thr Gly 
1               5                   10                  15      


Thr Ser Thr Asp Val Val Tyr Arg Ala Phe Asp Ile Tyr Asn Asp Lys 
            20                  25                  30          


Val Ala Gly Phe Ala Lys Phe Leu Lys Thr Asn Cys Cys Arg Phe Gln 
        35                  40                  45              


Glu Lys Asp Glu Asp Asp Asn Leu Ile Asp Ser Tyr Phe Val Val Lys 
    50                  55                  60                  


Arg His Thr Phe Ser Asn Tyr Gln His Glu Glu Thr Ile Tyr Asn Leu 
65                  70                  75                  80  


Leu Lys Asp Cys Pro Ala Val Ala Lys His Asp Phe Phe Lys Phe Arg 
                85                  90                  95      


Ile Asp Gly Asp Met Val Pro His Ile Ser Arg Gln Arg Leu Thr Lys 
            100                 105                 110         


Tyr Thr Met Ala Asp Leu Val Tyr Ala Leu Arg His Phe Asp Glu Gly 
        115                 120                 125             


Asn Cys Asp Thr Leu Lys Glu Ile Leu Val Thr Tyr Asn Cys Cys Asp 
    130                 135                 140                 


Asp Asp Tyr Phe Asn Lys Lys Asp Trp Tyr Asp Phe Val Glu Asn Pro 
145                 150                 155                 160 


Asp Ile Leu Arg Val Tyr Ala Asn Leu Gly Glu Arg Val Arg Gln Ala 
                165                 170                 175     


Leu Leu Lys Thr Val Gln Phe Cys Asp Ala Met Arg Asn Ala Gly Ile 
            180                 185                 190         


Val Gly Val Leu Thr Leu Asp Asn Gln Asp Leu Asn Gly Asn Trp Tyr 
        195                 200                 205             


Asp Phe Gly Asp Phe Ile Gln Thr Thr Pro Gly Ser Gly Val Pro Val 
    210                 215                 220                 


Val Asp Ser Tyr Tyr Ser Leu Leu Met Pro Ile Leu Thr Leu Thr Arg 
225                 230                 235                 240 


Ala Leu Thr Ala Glu Ser His Val Asp Thr Asp Leu Thr Lys Pro Tyr 
                245                 250                 255     


Ile Lys Trp Asp Leu Leu Lys Tyr Asp Phe Thr Glu Glu Arg Leu Lys 
            260                 265                 270         


Leu Phe Asp Arg Tyr Phe Lys Tyr Trp Asp Gln Thr Tyr His Pro Asn 
        275                 280                 285             


Cys Val Asn Cys Leu Asp Asp Arg Cys Ile Leu His Cys Ala Asn Phe 
    290                 295                 300                 


Asn Val Leu Phe Ser Thr Val Phe Pro Pro Thr Ser Phe Gly Pro Leu 
305                 310                 315                 320 


Val Arg Lys Ile Phe Val Asp Gly Val Pro Phe Val Val Ser Thr Gly 
                325                 330                 335     


Tyr His Phe Arg Glu Leu Gly Val Val His Asn Gln Asp Val Asn Leu 
            340                 345                 350         


His Ser Ser Arg Leu Ser Phe Lys Glu Leu Leu Val Tyr Ala Ala Asp 
        355                 360                 365             


Pro Ala Met His Ala Ala Ser Gly Asn Leu Leu Leu Asp Lys Arg Thr 
    370                 375                 380                 


Thr Cys Phe Ser Val Ala Ala Leu Thr Asn Asn Val Ala Phe Gln Thr 
385                 390                 395                 400 


Val Lys Pro Gly Asn Phe Asn Lys Asp Phe Tyr Asp Phe Ala Val Ser 
                405                 410                 415     


Lys Gly Phe Phe Lys Glu Gly Ser Ser Val Glu Leu Lys His Phe Phe 
            420                 425                 430         


Phe Ala Gln Asp Gly Asn Ala Ala Ile Ser Asp Tyr Asp Tyr Tyr Arg 
        435                 440                 445             


Tyr Asn Leu Pro Thr Met Cys Asp Ile Arg Gln Leu Leu Phe Val Val 
    450                 455                 460                 


Glu Val Val Asp Lys Tyr Phe Asp Cys Tyr Asp Gly Gly Cys Ile Asn 
465                 470                 475                 480 


Ala Asn Gln Val Ile Val Asn Asn Leu Asp Lys Ser Ala Gly Phe Pro 
                485                 490                 495     


Phe Asn Lys Trp Gly Lys Ala Arg Leu Tyr Tyr Asp Ser Met Ser Tyr 
            500                 505                 510         


Glu Asp Gln Asp Ala Leu Phe Ala Tyr Thr Lys Arg Asn Val Ile Pro 
        515                 520                 525             


Thr Ile Thr Gln Met Asn Leu Lys Tyr Ala Ile Ser Ala Lys Asn Arg 
    530                 535                 540                 


Ala Arg Thr Val Ala Gly Val Ser Ile Cys Ser Thr Met Thr Asn Arg 
545                 550                 555                 560 


Gln Phe His Gln Lys Leu Leu Lys Ser Ile Ala Ala Thr Arg Gly Ala 
                565                 570                 575     


Thr Val Val Ile Gly Thr Ser Lys Phe Tyr Gly Gly Trp His Asn Met 
            580                 585                 590         


Leu Lys Thr Val Tyr Ser Asp Val Glu Asn Pro His Leu Met Gly Trp 
        595                 600                 605             


Asp Tyr Pro Lys Cys Asp Arg Ala Met Pro Asn Met Leu Arg Ile Met 
    610                 615                 620                 


Ala Ser Leu Val Leu Ala Arg Lys His Thr Thr Cys Cys Ser Leu Ser 
625                 630                 635                 640 


His Arg Phe Tyr Arg Leu Ala Asn Glu Cys Ala Gln Val Leu Ser Glu 
                645                 650                 655     


Met Val Met Cys Gly Gly Ser Leu Tyr Val Lys Pro Gly Gly Thr Ser 
            660                 665                 670         


Ser Gly Asp Ala Thr Thr Ala Tyr Ala Asn Ser Val Phe Asn Ile Cys 
        675                 680                 685             


Gln Ala Val Thr Ala Asn Val Asn Ala Leu Leu Ser Thr Asp Gly Asn 
    690                 695                 700                 


Lys Ile Ala Asp Lys Tyr Val Arg Asn Leu Gln His Arg Leu Tyr Glu 
705                 710                 715                 720 


Cys Leu Tyr Arg Asn Arg Asp Val Asp Thr Asp Phe Val Asn Glu Phe 
                725                 730                 735     


Tyr Ala Tyr Leu Arg Lys His Phe Ser Met Met Ile Leu Ser Asp Asp 
            740                 745                 750         


Ala Val Val Cys Phe Asn Ser Thr Tyr Ala Ser Gln Gly Leu Val Ala 
        755                 760                 765             


Ser Ile Lys Asn Phe Lys Ser Val Leu Tyr Tyr Gln Asn Asn Val Phe 
    770                 775                 780                 


Met Ser Glu Ala Lys Cys Trp Thr Glu Thr Asp Leu Thr Lys Gly Pro 
785                 790                 795                 800 


His Glu Phe Cys Ser Gln His Thr Met Leu Val Lys Gln Gly Asp Asp 
                805                 810                 815     


Tyr Val Tyr Leu Pro Tyr Pro Asp Pro Ser Arg Ile Leu Gly Ala Gly 
            820                 825                 830         


Cys Phe Val Asp Asp Ile Val Lys Thr Asp Gly Thr Leu Met Ile Glu 
        835                 840                 845             


Arg Phe Val Ser Leu Ala Ile Asp Ala Tyr Pro Leu Thr Lys His Pro 
    850                 855                 860                 


Asn Gln Glu Tyr Ala Asp Val Phe His Leu Tyr Leu Gln Tyr Ile Arg 
865                 870                 875                 880 


Lys Leu His Asp Glu Leu Thr Gly His Met Leu Asp Met Tyr Ser Val 
                885                 890                 895     


Met Leu Thr Asn Asp Asn Thr Ser Arg Tyr Trp Glu Pro Glu Phe Tyr 
            900                 905                 910         


Glu Ala Met Tyr Thr Pro His Thr Val Leu Gln 
        915                 920             


