Table 1.
Mpro-boceprevir and Mpro-telaprevir interacting residues that are designed with corresponding SNPs of the wild-type sequence to emulate the mutations that are more likely to happen naturally over the evolution of the protein. Mutations reported in GISAID hCoV-19 with number of sequences from the pandemic are presented in brackets.
| S. No | Mpro-boceprevir interacting and designed wild-type residuesa | Sampled SNPs in designs | Mutations reported in GISAID hCoV-19 with number of sequences from the pandemic | S. No | Mpro-telaprevir interacting and designed wild-type residuesa | Sampled SNPs in designs | Mutations reported in GISAID hCoV-19 with number of sequences from the pandemic |
|---|---|---|---|---|---|---|---|
| 1 | T26 | ARNIKMPS | T26I (7), T26A (4) | 1 | T25 | ARNIKMPS | T25I (11), T25A (4) |
| 2 | L27 | RQHIMFPSWV | L27F (4), L27H (1) | 2 | T26 | ARNIKMPS | T26I (7), T26A (4) |
| 3 | M49 | RILKTV | M49I (68), M49T (12), M49V (4), M49R (1) | 3 | L27 | RQHIMFPSWV | L27F (4), L27H (1) |
| 4 | Y54 | NDCHFS | Y54F (1), Y54 N (1) | 4 | M49 | RILKTV | M49I (68), M49T (12), M49V (4), M49R (1) |
| 5 | L141 | RQHIMFPSWV | L141I (3), L141F (2), L141P (1) | 5 | L141 | RQHIMFPSWV | L141I (3), L141F (2), L141P (1) |
| 6 | N142 | DHIKSTY | N142S (18), N142I (8), N142L (5), N142D (4), N142K (1) | 6 | N142 | DHIKSTY | N142S (18), N142I (8), N142L (5), N142D (4), N142K (1) |
| 7 | G143 | ARDCESWV | G143S (11), G143V (5), G143C (4), G143D (1) | 7 | G143 | ARDCESWV | G143S (11), G143V (5), G143C (4), G143D (1) |
| 8 | S144 | ACLFPTWY | S144L (5), S144E (3), S144K (1), S144P (1) | 8 | S144 | ACLFPTWY | S144L (5), S144E (3), S144K (1), S144P (1) |
| 9 | H164 | RNDQLPY | H164 N (3), H164Y (2), H164P (1) | 9 | H164 | RNDQLPY | H164 N (3), H164Y (2), H164P (1) |
| 10 | M165 | RILKTV | M165I (10), M165K (4) | 10 | M165 | RILKTV | M165I (10), M165K (4) |
| 11 | E166 | ADQGKV | E166D (3), E166K (3), E166G (1) | 11 | E166 | ADQGKV | E166D (3), E166K (3), E166G (1) |
| 12 | K167 | RNQEIMT | L167S (2), L167F (1), L167I (1) | 12 | K167 | RNQEIMT | L167S (2), L167F (1), L167I (1) |
| 13 | P168 | ARQHLST | P168S (49), P168L (3), P168R (1) | 13 | P168 | ARQHLST | P168S (49), P168L (3), P168R (1) |
| 14 | D187 | ANEGHYV | D187Y (6), D187G (2), D187T (1) | 14 | V186 | ADEGILMF | V186F (55), V186I (5), V186A (3), V186L (2), V186D (1) |
| 15 | R188 | NCQGHILKMPSTW | R188K (22), R188S (15), R188 M (7), R188A (1), R188G (1) |
15 | D187 | ANEGHYV | D187Y (6), D187G (2), D187T (1) |
| 16 | Q189 | REHLKP | Q189K (43) | 16 | R188 | NCQGHILKMPSTW | R188K (22), R188S (15), R188 M (7), R188A (1), R188G (1) |
| 17 | T190 | ARNIKMPS | T190I (134), T190A (2), T190S (1) | 17 | Q189 | REHLKP | Q189K (43) |
| 18 | A191 | DEGPSTV | A191V (1240), A191T (9), A191S (7), A191E (1) | 18 | T190 | ARNIKMPS | T190I (134), T190A (2), T190S (1) |
| 19 | Q192 | REHLKP | Q192L (1) | 19 | A191 | DEGPSTV | A191V (1240), A191T (9), A191S (7), A191E (1) |
| 20 | Q192 | REHLKP | Q192L (1) |
a
The catalytic dyad residues H41 and C145 of Mpro were not considered in the design, as they carry out the acylation-deacylation reaction and cleavage of the substrates.