Table 1.
The list demonstrates the location and details of mutations of RdRp identified by CoVal webserver. The RdRp sequence reported from Wuhan, China was used as wild type sequence for this analysis. The 50217 sequences of RdRp reported from India (till Sept 2021) were used for identifying mutations and their frequency. The ΔΔG and ΔΔSvib ENCOM values were obtained by protein modelling using DynaMut programe. The positive and negative ΔΔG represents increase and decrease in protein stability upon mutation. Similarly, the positive and negative ΔΔSvib ENCOM represents the increase in flexibility and rigidity upon mutations. The mutation that localises in the unmodeled region of RdRp was not used in the analysis of ΔΔG and ΔΔSvib ENCOM and they were left blank (denotes by -) in table. P stands for Polar, NP stands for Non-Polar.
| Serial Number |
Nsp12 mutations | Polarity changes | Charge changes | Frequency of mutation | ΔΔG (kcal/mol) | ΔΔSVib ENCoM (kcal.mol-1.K-1) |
|---|---|---|---|---|---|---|
| 1 | A2V | NP to NP | Neutral to Neutral | 3 | – | – |
| 2 | S6L | P to NP | Neutral to Neutral | 12 | – | – |
| 3 | C12R | P to P | Neutral to Basic | 2 | – | – |
| 4 | A16V | NP to NP | Neutral to Neutral | 8 | – | – |
| 5 | A16E | NP to P | Neutral to Acidic | 2 | – | – |
| 6 | T20A | P to NP | Neutral to Neutral | 11 | – | – |
| 7 | G25D | NP to P | Neutral to Acidic | 4 | – | – |
| 8 | T26I | P to NP | Neutral to Neutral | 13 | – | – |
| 9 | Y32H | P to P | Neutral to Basic | 2 | −0.349 | 0.090 |
| 10 | D40A | P to NP | Acidic to Neutral | 4 | −0.139 | 0.021 |
| 11 | V42L | NP to NP | Neutral to Neutral | 2 | 0.347 | −0.342 |
| 12 | G44V | NP to NP | Neutral to Neutral | 2 | −1.011 | −0.103 |
| 13 | A46T | NP to P | Neutral to Neutral | 2 | −1.031 | −0.174 |
| 14 | K59 N | P to P | Basic to Neutral | 12 | – | – |
| 15 | D62Y | P to P | Acidic to Neutral | 3 | – | – |
| 16 | N64D | P to P | Neutral to Acidic | 2 | – | – |
| 17 | D67 N | P to P | Acidic to Neutral | 4 | – | – |
| 18 | T85I | P to NP | Neutral to Neutral | 14 | −0.707 | −0.074 |
| 19 | K91R | P to P | Basic to Basic | 11 | −0.143 | −0.066 |
| 20 | K91E | P to P | Basic to Acidic | 2 | −0.187 | 0.416 |
| 21 | K91 N | P to P | Basic to Neutral | 2 | −0.311 | 0.295 |
| 22 | P94L | NP to NP | Neutral to Neutral | 6 | 0.858 | −0.242 |
| 23 | P94S | NP to P | Neutral to Neutral | 3 | −0.035 | −0.131 |
| 24 | A95S | NP to P | Neutral to Neutral | 5 | −1.317 | −0.172 |
| 25 | A95V | NP to NP | Neutral to Neutral | 4 | −0.669 | −0.627 |
| 26 | A97V | NP to NP | Neutral to Neutral | 438 | 0.469 | −1.020 |
| 27 | G108V | NP to NP | Neutral to Neutral | 8 | – | – |
| 28 | D109G | P to NP | Acidic to Neutral | 3 | – | – |
| 29 | D109Y | P to P | Acidic to Neutral | 2 | – | – |
| 30 | R118C | P to P | Basic to Neutral | 4 | 0.005 | 0.055 |
| 31 | M124I | NP to NP | Neutral to Neutral | 6 | −0.088 | 0.250 |
| 32 | V128I | NP to NP | Neutral to Neutral | 5 | 1.237 | −0.268 |
| 33 | G137S | NP to P | Neutral to Neutral | 2 | −1.389 | 0.029 |
| 34 | C139S | P to P | Neutral to Neutral | 2 | −0.460 | −0.227 |
| 35 | D140Y | P to P | Acidic to Neutral | 6 | −0.105 | 0.035 |
| 36 | D140G | P to NP | Acidic to Neutral | 3 | −0.180 | 0.035 |
| 37 | T141I | P to NP | Neutral to Neutral | 11 | 1.041 | −0.231 |
| 38 | I145V | NP to NP | Neutral to Neutral | 4 | −0.190 | 0.408 |
| 39 | D153Y | P to P | Acidic to Neutral | 10 | 0.961 | 0.049 |
| 40 | D154G | P to NP | Acidic to Neutral | 2 | −0.771 | 0.111 |
| 41 | K160 N | P to P | Basic to Neutral | 6 | −0.089 | −0.029 |
| 42 | D161Y | P to P | Acidic to Neutral | 2 | 1.107 | −0.621 |
| 43 | W162C | NP to P | Neutral to Neutral | 3 | −1.169 | 1.004 |
| 44 | P169S | NP to P | Neutral to Neutral | 3 | 0.478 | −0.232 |
| 45 | D170G | P to NP | Acidic to Neutral | 3 | −0.527 | 0.156 |
| 46 | D170Y | P to P | Acidic to Neutral | 3 | −0.089 | 0.154 |
| 47 | R173S | P to P | Basic to Neutral | 4 | −0.412 | 0.203 |
| 48 | R173C | P to P | Basic to Neutral | 2 | −0.283 | 0.168 |
| 49 | R173H | P to P | Basic (strongly) to Basic (weakly) | 2 | −0.284 | 0.010 |
| 50 | A176T | NP to P | Neutral to Neutral | 2 | 0.032 | −0.721 |
| 51 | A185V | NP to NP | Neutral to Neutral | 11 | −0.179 | −0.369 |
| 52 | A185S | NP to P | Neutral to Neutral | 2 | – | – |
| 53 | A195D | NP to P | Neutral to Acidic | 2 | −0.478 | −0.397 |
| 54 | M196I | NP to NP | Neutral to Neutral | 7 | −0.554 | 0.094 |
| 55 | R197Q | P to P | Basic to Neutral | 3 | −0.483 | 0.096 |
| 56 | R197L | P to NP | Basic to Neutral | 2 | −0.109 | 0.109 |
| 57 | I223 M | NP to NP | Neutral to Neutral | 13 | −0.051 | −0.084 |
| 58 | T225I | P to NP | Neutral to Neutral | 2 | 0.090 | −0.076 |
| 59 | P227L | NP to NP | Neutral to Neutral | 245 | 0.360 | −0.332 |
| 60 | P227T | NP to P | Neutral to Neutral | 2 | 0.459 | −0.375 |
| 61 | G228S | NP to P | Neutral to Neutral | 18 | −1.113 | −0.158 |
| 62 | V231I | NP to NP | Neutral to Neutral | 3 | −0.529 | 0.229 |
| 63 | I244T | NP to P | Neutral to Neutral | 85 | −3.236 | 0.746 |
| 64 | T248I | P to NP | Neutral to Neutral | 7 | 0.452 | −0.080 |
| 65 | R249S | P to P | Basic to Neutral | 7 | −0.672 | 0.320 |
| 66 | R249G | P to NP | Basic to Neutral | 2 | −0.382 | 0.504 |
| 67 | R249 M | P to NP | Basic to Neutral | 2 | 0.825 | −0.111 |
| 68 | A250V | NP to NP | Neutral to Neutral | 5 | −0.237 | −0.482 |
| 69 | T252I | P to NP | Neutral to Neutral | 4 | 0.265 | −0.060 |
| 70 | A253V | NP to NP | Neutral to Neutral | 2 | −0.415 | −0.586 |
| 71 | E254D | P to P | Acidic to Acidic | 2 | −1.136 | 0.395 |
| 72 | H256Y | P to P | Basic to Neutral | 3 | −0.411 | −0.074 |
| 73 | V257F | NP to NP | Neutral to Neutral | 5 | −0.485 | 0.162 |
| 74 | K263 N | P to P | Basic to Neutral | 5 | −0.336 | 0.316 |
| 75 | P264S | NP to P | Neutral to Neutral | 4 | −0.715 | 0.098 |
| 76 | D269 N | P to P | Acidic to Neutral | 34 | −0.258 | 0.080 |
| 77 | L270F | NP to NP | Neutral to Neutral | 3 | 0.390 | −0.209 |
| 78 | E278D | P to P | Acidic to Acidic | 3 | −0.714 | 0.103 |
| 79 | R279S | P to P | Basic to Neutral | 3 | −2.849 | 1.063 |
| 80 | L282I | NP to NP | Neutral to Neutral | 3 | −0.287 | 0.096 |
| 81 | D284Y | P to P | Acidic to Neutral | 7 | 0.346 | −0.459 |
| 82 | Q292H | P to P | Neutral to Basic | 2 | 0.171 | 0.070 |
| 83 | T293I | P to NP | Neutral to Neutral | 5 | 0.264 | −0.016 |
| 84 | V299F | NP to NP | Neutral to Neutral | 4 | 0.240 | −0.143 |
| 85 | L302F | NP to NP | Neutral to Neutral | 3 | −0.363 | 0.045 |
| 86 | A311S | NP to P | Neutral to Neutral | 8 | −0.229 | −0.014 |
| 87 | V315A | NP to NP | Neutral to Neutral | 3 | −1.724 | 0.711 |
| 88 | F317L | NP to NP | Neutral to Neutral | 2 | 0.045 | 0.379 |
| 89 | T319I | P to NP | Neutral to Neutral | 35 | 1.052 | −0.244 |
| 90 | P323L | NP to NP | Neutral to Neutral | 11094 | 0.530 | −0.252 |
| 91 | P323F | NP to NP | Neutral to Neutral | 24 | 0.297 | −0.199 |
| 92 | P323V | NP to NP | Neutral to Neutral | 3 | 0.578 | −0.313 |
| 93 | S325I | P to NP | Neutral to Neutral | 2 | 1.763 | −0.574 |
| 94 | P328S | NP to P | Neutral to Neutral | 2 | −0.425 | 0.065 |
| 95 | L329I | NP to NP | Neutral to Neutral | 15 | 0.081 | 0.231 |
| 96 | V330A | NP to NP | Neutral to Neutral | 38 | – | – |
| 97 | V330L | NP to NP | Neutral to Neutral | 5 | 0.025 | −0.103 |
| 98 | G337C | NP to P | Neutral to Neutral | 2 | −1.187 | 0.219 |
| 99 | Y346H | P to P | Neutral to Basic | 2 | −0.021 | 0.619 |
| 100 | V354L | NP to NP | Neutral to Neutral | 21 | −0.162 | −0.387 |
| 101 | V354A | NP to NP | Neutral to Neutral | 4 | −1.811 | 0.277 |
| 102 | Q357H | P to P | Neutral to Basic | 7 | 1.218 | −0.094 |
| 103 | D358G | P to NP | Acidic to Neutral | 3 | −0.096 | 0.357 |
| 104 | A379V | NP to NP | Neutral to Neutral | 7 | 0.624 | −0.529 |
| 105 | A379S | NP to P | Neutral to Neutral | 2 | 1.586 | −0.510 |
| 106 | M380I | NP to NP | Neutral to Neutral | 6 | −0.487 | 0.551 |
| 107 | A382V | NP to NP | Neutral to Neutral | 3 | 0.596 | −0.438 |
| 108 | A383S | NP to P | Neutral to Neutral | 2 | −0.131 | −0.021 |
| 109 | T394 M | P to NP | Neutral to Neutral | 3 | 0.947 | −0.648 |
| 110 | A400S | NP to P | Neutral to Neutral | 52 | 0.437 | −0.127 |
| 111 | T402I | P to NP | Neutral to Neutral | 6 | 0.301 | 0.039 |
| 112 | V405F | NP to NP | Neutral to Neutral | 3 | 0.955 | −0.639 |
| 113 | A406S | NP to P | Neutral to Neutral | 7 | 0.497 | −0.246 |
| 114 | A406V | NP to NP | Neutral to Neutral | 2 | −0.148 | −0.047 |
| 115 | D418E | P to P | Acidic to Acidic | 2 | 0.915 | −0.258 |
| 116 | A423V | NP to NP | Neutral to Neutral | 12 | 0.732 | −0.338 |
| 117 | S434Y | P to P | Neutral to Neutral | 2 | 0.277 | −0.606 |
| 118 | V435I | NP to NP | Neutral to Neutral | 4 | 0.150 | −0.391 |
| 119 | V435F | NP to NP | Neutral to Neutral | 2 | −0.063 | −1.096 |
| 120 | A443V | NP to NP | Neutral to Neutral | 4 | 0.937 | −0.250 |
| 121 | A443S | NP to P | Neutral to Neutral | 2 | −0.013 | −0.135 |
| 122 | Q444H | P to P | Neutral to Basic | 5 | 1.310 | −0.346 |
| 123 | A449V | NP to NP | Neutral to Neutral | 7 | 0.871 | −0.560 |
| 124 | A449S | NP to P | Neutral to Neutral | 2 | −0.265 | 0.016 |
| 125 | I450V | NP to NP | Neutral to Neutral | 2 | −1.121 | 0.580 |
| 126 | Y458H | P to P | Neutral to Basic | 3 | −0.169 | 0.293 |
| 127 | P461S | NP to P | Neutral to Neutral | 8 | −0.475 | 0.055 |
| 128 | M463I | NP to NP | Neutral to Neutral | 19 | 0.483 | 0.250 |
| 129 | C464F | P to NP | Neutral to Neutral | 2 | 1.251 | −1.092 |
| 130 | I466T | NP to P | Neutral to Neutral | 2 | −2.428 | 0.355 |
| 131 | V473F | NP to NP | Neutral to Neutral | 24 | −0.802 | −0.941 |
| 132 | V476A | NP to NP | Neutral to Neutral | 3 | −0.477 | 0.578 |
| 133 | K478 N | P to P | Basic to Neutral | 60 | −1.105 | 0.533 |
| 134 | I494V | NP to NP | Neutral to Neutral | 2 | −0.044 | 0.027 |
| 135 | L514F | NP to NP | Neutral to Neutral | 2 | −0.300 | −0.066 |
| 136 | Y521H | P to P | Neutral to Basic | 4 | −0.048 | 0.764 |
| 137 | A526V | NP to NP | Neutral to Neutral | 4 | 0.305 | −0.109 |
| 138 | A526S | NP to P | Neutral to Neutral | 3 | −0.315 | −0.121 |
| 139 | A529V | NP to NP | Neutral to Neutral | 16 | −0.273 | −0.068 |
| 140 | A529T | NP to P | Neutral to Neutral | 3 | −0.874 | 0.002 |
| 141 | A529S | NP to P | Neutral to Neutral | 2 | −0.884 | −0.059 |
| 142 | I536T | NP to P | Neutral to Neutral | 3 | – | – |
| 143 | L544I | NP to NP | Neutral to Neutral | 7 | 0.224 | 0.060 |
| 144 | A544V | NP to NP | Neutral to Neutral | 2 | 0.325 | −0.547 |
| 145 | I562V | NP to NP | Neutral to Neutral | 2 | −0.801 | 0.215 |
| 146 | I579V | NP to NP | Neutral to Neutral | 3 | −0.573 | 0.414 |
| 147 | T586P | P to NP | Neutral to Neutral | 2 | −0.213 | 0.662 |
| 148 | V588L | NP to NP | Neutral to Neutral | 4 | 0.599 | −0.117 |
| 149 | T591I | P to NP | Neutral to Neutral | 4 | 1.218 | −0.416 |
| 150 | M601I | NP to NP | Neutral to Neutral | 18 | −0.362 | −0.033 |
| 151 | V605A | NP to NP | Neutral to Neutral | 18 | −1.528 | 0.596 |
| 152 | H613Y | P to P | Basic to Neutral | 20 | 0.836 | −0.213 |
| 153 | M629I | NP to NP | Neutral to Neutral | 6 | −0.428 | 0.170 |
| 154 | L636F | NP to NP | Neutral to Neutral | 4 | −0.115 | −0.435 |
| 155 | L636I | NP to NP | Neutral to Neutral | 2 | 0.569 | 0.041 |
| 156 | L638F | NP to NP | Neutral to Neutral | 6 | −0.167 | −0.297 |
| 157 | T643I | P to NP | Neutral to Neutral | 10 | −0.383 | −0.074 |
| 158 | T644 M | P to NP | Neutral to Neutral | 3 | −0.084 | −0.037 |
| 159 | S647I | P to NP | Neutral to Neutral | 29 | −0.272 | 0.166 |
| 160 | S649L | P to NP | Neutral to Neutral | 2 | 0.684 | −0.422 |
| 161 | A656S | NP to P | Neutral to Neutral | 20 | −1.416 | 0.063 |
| 162 | M666I | NP to NP | Neutral to Neutral | 6 | −0.229 | 0.365 |
| 163 | M668I | NP to NP | Neutral to Neutral | 11 | 0.104 | 0.066 |
| 164 | G671S | NP to P | Neutral to Neutral | 2665 | 0.786 | −0.246 |
| 165 | G671A | NP to NP | Neutral to Neutral | 2 | 1.315 | −0.906 |
| 166 | V675I | NP to NP | Neutral to Neutral | 49 | 0.050 | −0.115 |
| 167 | C697F | P to NP | Neutral to Neutral | 3 | −1.055 | −0.979 |
| 168 | A699S | NP to P | Neutral to Neutral | 4 | −2.233 | −0.185 |
| 169 | T710 N | P to P | Neutral to Neutral | 2 | 0.703 | −0.185 |
| 170 | A716T | NP to P | Neutral to Neutral | 2 | 0.285 | −0.035 |
| 171 | K718 N | P to P | Basic to Neutral | 5 | −0.208 | 0.051 |
| 172 | H725Y | P to P | Basic to Neutral | 6 | 0.240 | 0.166 |
| 173 | E729K | P to P | Acidic to Basic | 2 | 0.825 | −0.139 |
| 174 | N734D | P to P | Neutral to Acidic | 4 | −0.338 | 0.227 |
| 175 | D736 N | P to P | Acidic to Neutral | 3 | 0.006 | −0.049 |
| 176 | D738Y | P to P | Acidic to Neutral | 5 | 0.861 | −0.137 |
| 177 | T739I | P to NP | Neutral to Neutral | 4 | 0.272 | 0.008 |
| 178 | E744D | P to P | Acidic to Acidic | 11 | −0.566 | 0.229 |
| 179 | M756I | NP to NP | Neutral to Neutral | 11 | 1.019 | 0.205 |
| 180 | S768 N | P to P | Neutral to Neutral | 2 | −0.152 | −0.012 |
| 181 | G774C | NP to P | Neutral to Neutral | 4 | 0.107 | −0.086 |
| 182 | L775P | NP to NP | Neutral to Neutral | 2 | −0.600 | 0.754 |
| 183 | V776L | NP to NP | Neutral to Neutral | 3 | −0.017 | −0.160 |
| 184 | S778C | P to P | Neutral to Neutral | 3 | 0.409 | −0.305 |
| 185 | S778 N | P to P | Neutral to Neutral | 2 | 0.687 | −0.195 |
| 186 | K780R | P to P | Basic to Basic | 5 | 1.115 | −0.590 |
| 187 | E796D | P to P | Acidic to Acidic | 4 | −0.269 | 0.244 |
| 188 | T801I | P to NP | Neutral to Neutral | 5 | 0.114 | −0.047 |
| 189 | L803I | NP to NP | Neutral to Neutral | 2 | 0.397 | −0.105 |
| 190 | L805I | NP to NP | Neutral to Neutral | 3 | −0.189 | 0.217 |
| 191 | T806I | P to NP | Neutral to Neutral | 29 | 0.151 | −0.065 |
| 192 | P809R | NP to P | Neutral to Basic | 5 | −0.615 | −0.234 |
| 193 | M818I | NP to NP | Neutral to Neutral | 2 | 0.129 | 0.221 |
| 194 | Q822H | P to P | Neutral to Basic | 60 | 0.006 | 0.514 |
| 195 | Q822K | P to P | Neutral to Basic | 2 | 1.801 | −0.467 |
| 196 | G823C | NP to P | Neutral to Neutral | 4 | 0.442 | −0.644 |
| 197 | G823D | NP to P | Neutral to Acidic | 2 | 0.467 | −0.400 |
| 198 | D824Y | P to P | Acidic to Neutral | 6 | −0.451 | 0.111 |
| 199 | V827L | NP to NP | Neutral to Neutral | 3 | 0.471 | −0.340 |
| 200 | L829F | NP to NP | Neutral to Neutral | 4 | −1.408 | 0.045 |
| 201 | P834L | NP to NP | Neutral to Neutral | 3 | 1.266 | −0.943 |
| 202 | V848L | NP to NP | Neutral to Neutral | 12 | 0.194 | −0.201 |
| 203 | V848I | NP to NP | Neutral to Neutral | 2 | −0.732 | 0.119 |
| 204 | M855I | NP to NP | Neutral to Neutral | 6 | −0.312 | 0.223 |
| 205 | I856V | NP to NP | Neutral to Neutral | 2 | −0.635 | 0.307 |
| 206 | T870I | P to NP | Neutral to Neutral | 10 | 0.654 | −0.440 |
| 207 | P873S | NP to P | Neutral to Neutral | 6 | −0.054 | 0.023 |
| 208 | E876D | P to P | Acidic to Acidic | 2 | −1.338 | 1.031 |
| 209 | A878S | NP to P | Neutral to Neutral | 2 | 1.053 | −0.488 |
| 210 | D879Y | P to P | Acidic to Neutral | 6 | 1.218 | −0.559 |
| 211 | V880I | NP to NP | Neutral to Neutral | 34 | −0.087 | −0.146 |
| 212 | D893Y | P to P | Acidic to Neutral | 7 | 0.088 | −0.168 |
| 213 | T896I | P to NP | Neutral to Neutral | 2 | – | – |
| 214 | M899I | NP to NP | Neutral to Neutral | 4 | – | – |
| 215 | V905I | NP to NP | Neutral to Neutral | 38 | – | – |
| 216 | M906I | NP to NP | Neutral to Neutral | 2 | – | – |
| 217 | T908I | P to NP | Neutral to Neutral | 5 | – | – |
| 218 | S913L | P to NP | Neutral to Neutral | 19 | −0.116 | 0.012 |
| 219 | R914K | P to P | Basic to Basic | 9 | −0.240 | 0.168 |
| 220 | P918L | NP to NP | Neutral to Neutral | 4 | 0.199 | −0.711 |
| 221 | E922D | P to P | Acidic to Acidic | 8 | −1.106 | 0.193 |
| 222 | T929I | P to NP | Neutral to Neutral | 2 | 0.075 | 4.551 |
| 223 | Q932H | P to P | Neutral to Basic | 2 | 1.077 | −4.934 |