Tracking the relevant researches of CADD drug development against COVID-19
Spike protein S1: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein. Binding to host NRP1 and NRP2 via C-terminal polybasic sequence enhances virion entry into host cell. This interaction may explain virus tropism of human olfactory epithelium cells, which express high level of NRP1 and NRP2 but low level of ACE2. The stalk domain of S contains three hinges, giving the head unexpected orientational freedom. Uses human TMPRSS2 for priming in human lung cells which is an essential step for viral entry. Can be alternatively processed by host furin. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. Spike protein S2: mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Spike protein S2': Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis. [Uniprot]
Chain A: S19 T20 I21 E22 E23 Q24 K26 T27 F28 L29 D30 K31 F32 N33 H34 E35 E37 D38 L39 F40 Y41 Q42 L45 W48 N49 N61 K68 F72 Q76 L79 Y83 Q89 V93 Q96 M323 T324 Q325 G326 F327 W328 E329 N330 D350 G352 K353 G354 D355 F356 R357 I379 M383 A386 A387 Q388 P389 F390 R393
Chain E: R346 S349 Y351 S375 T376 V401 R403 G404 D405 E406 V407 R408 Q409 G416 K417 D420 Y421 N437 N439 N440 L441 D442 S443 K444 V445 G446 G447 N448 Y449 N450 Y451 L452 Y453 R454 F456 R457 K458 S459 N460 D467 S469 T470 E471 I472 Y473 Q474 A475 G476 S477 T478 P479 C480 N481 G482 V483 E484 G485 F486 N487 C488 Y489 F490 P491 L492 Q493 S494 Y495 G496 F497 Q498 P499 T500 N501 G502 V503 G504 Y505 Q506 P507 Y508
Chain E: R346 S349 Y351 S375 T376 V401 R403 G404 D405 E406 V407 R408 Q409 G416 K417 D420 Y421 N437 N439 N440 L441 D442 S443 K444 V445 G446 G447 N448 Y449 N450 Y451 L452 Y453 R454 L455 F456 R457 K458 S459 N460 D467 S469 T470 E471 I472 Y473 Q474 A475 G476 S477 T478 P479 C480 N481 G482 V483 E484 G485 F486 N487 C488 Y489 F490 P491 L492 Q493 S494 Y495 G496 F497 Q498 P499 T500 N501 G502 V503 G504 Y505 Q506 P507 Y508
Chain A: N30 T33 F43 S45 S46 V47 L48 H49 S50 P57 F58 F59 S60 Q218 F220 R273 T274 L276 K278 Y279 N280 E281 T286 D287 A288 V289 D290 C291 A292 L293 D294 P295 L296 S297 E298 T299 K300 C301 T302 L303 K304 S305 F306 T307 V308 E309 K310 G311 I312 Y313 Q314 T315 S316 N317 F318 R319 V320 Q321 K557 R567 D568 I569 A570 T572 T573 D574 D586 I587 T588 P589 C590 S591 F592 G593 G594 V595 S596 V597 I598 T599 P600 G601 T602 N603 T604 S605 N606 E607 V608 A609 V610 L611 Y612 Q613 D614 V615 N616 E619 V620 N641 F643 Q644 T645 R646 A647 G648 L650 I651 G652 A653 E654 H655 V656 N657 N658 S659 Y660 E661 C662 D663 I664 P665 I666 G667 A668 G669 I670 A672 S673 Y674 Q675 T676 Q690 S691 I692 I693 A694 Y695 T696 M697 S698 L699 G700 A701 E702 N703 S704 V705 A706 Y707 S708 N709 N710 S711 I712 A713 I714 P715 T716 N717 F718 T719 I720 S721 V722 T723 T724 E725 I726 L727 P728 V729 S730 M731 T732 K733 T734 S735 V736 D737 C738 T739 Y741 G757 S758 F759 C760 T761 Q762 L763 N764 R765 A766 L767 T768 G769 I770 A771 V772 E773 Q774 D775 K776 N777 T778 Q779 E780 V781 F782 A783 Q784 V785 K786 Q787 I788 Y789 K790 T791 P792 P793 I794 K795 D796 F797 G798 G799 F800 N801 F802 S803 Q804 I805 L806 P807 D808 P809 S810 K811 S813 K814 R815 S816 F817 I818 E819 D820 L821 L822 F823 N824 K825 V826 T827 F855 N856 G857 L858 T859 V860 L861 P862 P863 L864 L865 T866 D867 E868 M869 I870 A871 Q872 Y873 T874 S875 L877 L878 A879 T881 I882 S884 G885 W886 T887 F888 G889 A890 G891 A892 A893 L894 Q895 I896 P897 F898 A899 M900 Q901 M902 A903 Y904 R905 F906 N907 G908 I909 G910 V911 T912 Q913 N914 V915 L916 Y917 E918 N919 Q920 K921 L922 I923 A924 N925 Q926 F927 N928 S929 A930 I931 G932 K933 I934 Q935 D936 S937 L938 S939 S940 T941 A942 S943 A944 L945 G946 K947 L948 Q949 D950 V951 V952 N953 Q954 N955 A956 Q957 A958 L959 N960 T961 L962 V963 K964 Q965 Q1002 S1003 L1004 Q1005 T1006 Y1007 V1008 T1009 Q1010 Q1011 L1012 I1013 R1014 A1015 A1016 E1017 I1018 R1019 A1020 S1021 A1022 N1023 L1024 A1026 T1027 K1028 S1030 E1031 C1032 V1033 L1034 G1035 Q1036 S1037 K1038 R1039 V1040 D1041 F1042 C1043 G1044 K1045 G1046 Y1047 H1048 L1049 M1050 S1051 F1052 P1053 Q1054 S1055 A1056 P1057 H1058 G1059 V1061 L1063 H1064 V1065 T1066 Y1067 V1068 P1069 A1070 Q1071 E1072 K1073 N1074 F1075 T1076 T1077 A1078 P1079 P1090 R1091 E1092 G1093 V1094 F1095 T1105 Q1106 R1107 N1108 F1109 Y1110 E1111 F1121 V1128 I1130 G1131
Chain B: F43 R44 S45 S46 V47 L48 H49 S50 K206 F220 S221 A222 T274 F275 L276 K278 Y279 N280 E281 T284 I285 T286 D287 A288 V289 C291 A292 P295 L296 S297 E298 T299 K300 C301 T302 L303 K304 S305 F306 T307 V308 E309 K310 G311 I312 Y313 Q314 T315 S316 N317 F318 R319 V320 V551 T553 E554 S555 N556 K557 K558 R567 D568 I569 A570 D571 T572 T573 D574 D586 I587 T588 P589 C590 S591 F592 G593 G594 V595 S596 V597 I598 T599 P600 G601 T602 N603 T604 N606 V610 L611 Y612 Q613 D614 V615 N616 E619 Q644 T645 R646 A647 G648 L650 S659 Y660 E661 C662 D663 I664 P665 I666 G667 A668 G669 I670 S673 Y674 Y695 T696 M697 S698 L699 G700 A701 E702 N703 S704 V705 A706 Y707 S708 N709 N710 S711 I712 A713 I714 P715 T716 N717 F718 T719 I720 S721 V722 T723 T724 E725 I726 L727 P728 V729 S730 M731 T732 K733 T734 S735 V736 D737 C738 T739 M740 Y741 L753 L754 G757 S758 F759 C760 T761 Q762 L763 N764 R765 A766 L767 T768 G769 I770 A771 V772 E773 Q774 D775 K776 N777 T778 Q779 E780 V781 F782 A783 Q784 V785 K786 Q787 I788 Y789 K790 T791 P792 P793 I794 K795 D796 F797 G798 G799 F800 N801 F802 S803 Q804 I805 L806 P807 D808 P809 K811 S813 K814 R815 S816 F817 I818 E819 D820 L821 L822 F823 N824 K825 V826 T827 K854 F855 N856 G857 L858 T859 V860 L861 P862 P863 L864 L865 T866 D867 E868 M869 I870 A871 Q872 Y873 T874 S875 L878 A879 T881 I882 T883 S884 G885 W886 T887 F888 G889 A890 G891 A892 A893 L894 Q895 I896 P897 F898 A899 M900 Q901 M902 A903 Y904 R905 F906 N907 G908 I909 G910 V911 T912 Q913 V915 L916 Y917 E918 N919 Q920 K921 L922 I923 A924 N925 Q926 F927 N928 S929 A930 I931 G932 K933 I934 Q935 D936 S937 L938 S939 S940 T941 A942 S943 A944 L945 G946 K947 L948 Q949 D950 V951 V952 N953 Q954 N955 A956 Q957 A958 L959 N960 T961 L962 V963 K964 Q965 L966 S967 R1000 L1001 Q1002 S1003 L1004 Q1005 T1006 Y1007 V1008 T1009 Q1010 Q1011 L1012 I1013 R1014 A1015 A1016 E1017 I1018 R1019 A1020 S1021 A1022 N1023 L1024 A1026 T1027 K1028 S1030 E1031 C1032 V1033 L1034 G1035 Q1036 S1037 K1038 R1039 V1040 D1041 F1042 C1043 G1044 K1045 G1046 Y1047 H1048 L1049 M1050 S1051 F1052 P1053 Q1054 S1055 A1056 P1057 H1058 G1059 V1061 L1063 H1064 V1065 T1066 Y1067 V1068 P1069 A1070 Q1071 E1072 K1073 N1074 F1075 T1076 T1077 A1078 P1079 P1090 R1091 E1092 G1093 V1094 F1095 S1097 N1098 W1102 V1104 T1105 Q1106 R1107 N1108 F1109 Y1110 E1111 F1121 S1123 D1127 V1128 V1129 I1130 G1131 V1133
Chain C: F43 R44 S45 S46 V47 L48 H49 S50 T274 L276 K278 Y279 E281 N282 C291 A292 L293 D294 P295 E298 C301 T302 L303 K304 S305 F306 T307 V308 E309 K310 G311 I312 Y313 Q314 T315 S316 N317 F318 R319 V320 N536 V551 T553 N556 K557 R567 D568 I569 A570 D574 D586 I587 T588 P589 C590 S591 F592 G593 G594 V595 S596 V597 I598 P600 G601 T602 N603 V608 A609 V610 L611 Y612 Q613 D614 V615 N616 C617 T618 E619 V620 N641 V642 F643 Q644 T645 R646 A647 G648 C649 L650 I651 G652 A653 H655 V656 N657 N658 S659 Y660 E661 C662 D663 I664 P665 I666 G667 A668 G669 I670 A672 S673 Y674 Q675 I692 A694 Y695 T696 M697 S698 L699 G700 A701 E702 N703 S704 V705 A706 Y707 S708 N709 N710 S711 I712 A713 I714 P715 T716 N717 F718 T719 I720 S721 V722 T723 T724 E725 I726 L727 P728 V729 S730 M731 T732 K733 T734 S735 V736 D737 C738 T739 M740 G757 S758 F759 C760 T761 Q762 L763 N764 R765 A766 L767 T768 G769 I770 A771 V772 E773 Q774 D775 K776 N777 T778 Q779 E780 V781 F782 A783 Q784 V785 K786 Q787 I788 Y789 K790 T791 P792 P793 I794 K795 D796 F797 G798 G799 F800 N801 F802 S803 Q804 I805 L806 P807 D808 P809 S810 K811 S813 K814 R815 S816 F817 I818 E819 D820 L821 L822 F823 N824 K825 V826 T827 N856 G857 L858 T859 V860 L861 P862 P863 L864 L865 T866 D867 E868 M869 I870 A871 Q872 Y873 T874 S875 L878 A879 T881 T883 S884 G885 W886 T887 F888 G889 A890 G891 A892 A893 L894 Q895 I896 P897 F898 A899 M900 Q901 M902 A903 Y904 R905 F906 N907 G908 I909 G910 V911 T912 Q913 N914 V915 L916 Y917 E918 N919 Q920 K921 L922 I923 A924 N925 Q926 F927 N928 S929 A930 I931 G932 K933 I934 Q935 D936 S937 L938 S939 S940 T941 A942 S943 A944 L945 G946 K947 L948 Q949 D950 V951 V952 N953 Q954 N955 A956 Q957 A958 L959 N960 T961 L962 V963 K964 Q965 Q1002 S1003 L1004 Q1005 T1006 Y1007 V1008 T1009 Q1010 Q1011 L1012 I1013 R1014 A1015 A1016 E1017 I1018 R1019 A1020 S1021 A1022 N1023 L1024 A1026 T1027 K1028 S1030 E1031 V1033 L1034 G1035 Q1036 S1037 K1038 R1039 V1040 D1041 F1042 C1043 G1044 K1045 G1046 Y1047 H1048 L1049 M1050 S1051 F1052 Q1054 S1055 A1056 P1057 H1058 G1059 V1061 L1063 H1064 V1065 T1066 Y1067 V1068 P1069 A1070 Q1071 E1072 K1073 N1074 F1075 T1076 T1077 A1078 P1079 P1090 R1091 E1092 G1093 V1094 F1095 V1096 S1097 N1098 G1099 W1102 V1104 T1105 Q1106 R1107 N1108 F1109 Y1110 E1111 P1112 Q1113 F1121 V1128 I1130 G1131 V1133