Table 1. Selected amino acid variants of papain-like protease from SARS-CoV-2.
Frequent mutations are those with mutation rate >0.002. Residues from inhibitor binding site were selected based on residue-ligand distance (no more than 6 Å) calculated for all available PLpro-ligand crystal structures. Amino acids in Variants column are sorted from most to least frequent. All found variants are available in Supplementary Material.
| Amino acid | Position (PLpro) | Position (NSP3) | Position (ORF1a) | Variants | Number of mutated sequences | Mutation Rate |
|---|---|---|---|---|---|---|
| Inhibitor binding | ||||||
| A | 107 | 852 | 1670 | V, T, S, Q, E | 1624 | 0.00062 |
| D | 108 | 853 | 1671 | A, G, Y, N, E, V, K | 281 | 0.00010 |
| N | 109 | 854 | 1672 | D, S, K | 76 | 0.00003 |
| Y | 112 | 857 | 1675 | H,C,F,N | 48 | 0.00002 |
| K | 157 | 902 | 1720 | N, R, T, G, M | 1002 | 0.00038 |
| E | 161 | 906 | 1724 | D, G, A, K, V | 4819 | 0.00185 |
| L | 162 | 907 | 1725 | F, S, V, I | 48 | 0.00002 |
| G | 163 | 908 | 1726 | C, S, A, D | 311 | 0.00012 |
| D | 164 | 909 | 1727 | G, E, S, N | 17 | 0.00000 |
| V | 165 | 910 | 1728 | I, A, F, D, L | 424 | 0.00016 |
| R | 166 | 911 | 1729 | K | 11 | 0.00000 |
| E | 167 | 912 | 1730 | D, V, A, G, K | 16 | 0.00000 |
| M | 208 | 953 | 1771 | T, I, V, L, K, R, A, G | 1436 | 0.00055 |
| A | 246 | 991 | 1809 | T, V, S, E, G | 1130 | 0.00043 |
| P | 247 | 992 | 1810 | L, S, Q, T | 2012 | 0.00077 |
| P | 248 | 993 | 1811 | L, S, F, H | 144 | 0.00006 |
| A | 249 | 994 | 1812 | V, D, T, S, G | 1187 | 0.00045 |
| Q | 250 | 995 | 1813 | H, L, R, P, K, E | 1709 | 0.00065 |
| Y | 264 | 1009 | 1827 | H | 4 | 0.00000 |
| G | 266 | 1011 | 1829 | D | 9 | 0.00000 |
| N | 267 | 1012 | 1830 | D, S, T, K, I, Y | 260 | 0.00010 |
| Y | 268 | 1013 | 1831 | H, C, F, D, N | 123 | 0.00005 |
| Q | 269 | 1014 | 1832 | K, L, R, H | 147 | 0.00006 |
| C | 270 | 1015 | 1833 | Y, R, F, G, S, W | 749 | 0.00029 |
| P | 299 | 1044 | 1862 | S, L, H, T, R | 3657 | 0.00140 |
| T | 301 | 1046 | 1864 | A, M, S, R | 48 | 0.00002 |
| D | 302 | 1047 | 1865 | N, E, M, Y | 99 | 0.00004 |
| The most frequent mutations | ||||||
| A | 145 | 890 | 1708 | D, V, S, T, G, P, N | 193489 | 0.07411 |
| P | 77 | 822 | 1640 | L, S, H, F, T, R, I | 147359 | 0.05644 |
| E | 70 | 815 | 1633 | D, G, Y, A, K, V | 32190 | 0.01233 |
| K | 232 | 977 | 1795 | Q, T, N, R, E, I | 26076 | 0.00999 |
| T | 259 | 1004 | 1822 | I, A, N, S, V | 12808 | 0.00491 |
| T | 277 | 1022 | 1840 | I, N, A, F, S | 10561 | 0.00404 |
| A | 116 | 861 | 1679 | S, V, T, E, G | 9614 | 0.00368 |
| S | 24 | 769 | 1587 | S, P, A, T, N, Y | 7360 | 0.00282 |
| M | 23 | 768 | 1586 | I, V, L, T, K | 6666 | 0.00255 |
| K | 92 | 837 | 1655 | N, R, E, Q, T, M, G | 6510 | 0.00249 |
| P | 223 | 968 | 1786 | L, S, H, F, T | 6013 | 0.00230 |
| T | 191 | 936 | 1754 | I, N, A, S, P | 5963 | 0.00228 |