Emerging Mutations in Nsp1 of SARS-CoV-2 and Their Effect on the Structural Stability
Abstract
:1. Background
2. Methodology
2.1. Genome Sequence Retrieval
2.2. Genome Sequence Alignment
2.3. Nsp1 Structural Information
2.4. Missing Residues and Full-Length Nsp1
2.5. Mutations’ Effects on Nsp1 Stability and Flexibility
3. Results
Effect of Mutations on Nsp1′s Stability and Flexibility
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
GISAID | Global Initiative Sharing All Influenza Data |
Nsp | Non-structural protein |
ORF | Open reading frame |
SARS-CoV | Severe acute respiratory syndrome coronavirus |
SARS-CoV-2 | Severe acute respiratory syndrome coronavirus 2 |
(COVID-19) | Coronavirus disease 19 |
MT | Mutants |
PDB | Protein Data Bank |
WT | Wild type |
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Mutation | Frequency | * ΔΔG: kcal/mol | Stability | * ΔΔSVib ENCoM kcal.mol−1.K−1 | Flexibility |
---|---|---|---|---|---|
R24C | 1122 | −0.218 | Destabilizing | 0.158 | Increase |
E37D | 237 | −0.844 | Destabilizing | 0.348 | Increase |
E37K | 309 | −0.243 | Destabilizing | 0.360 | Increase |
H45Y | 143 | 1.262 | Stabilizing | −0.217 | Decrease |
D48G | 881 | −0.217 | Destabilizing | 0.024 | Increase |
V56I | 113 | 0.954 | Stabilizing | −0.228 | Decrease |
E57G | 212 | 0.332 | Stabilizing | −0.112 | Decrease |
V60I | 188 | 0.617 | Stabilizing | −0.192 | Decrease |
D75E | 890 | 0.31 | Stabilizing | −0.035 | Decrease |
D75G | 115 | 0.676 | Stabilizing | −0.066 | Decrease |
M85V | 184 | −0.105 | Destabilizing | 0.687 | Increase |
E87D | 407 | −1.088 | Destabilizing | 0.395 | Increase |
L92F | 199 | 0.143 | Stabilizing | −0.002 | Decrease |
H110Y | 860 | 0.452 | Stabilizing | −0.060 | Decrease |
K120N | 418 | −0.320 | Destabilizing | 0.129 | Increase |
R124C | 126 | −1.116 | Destabilizing | 1.056 | Increase |
N126S | 209 | −0.692 | Destabilizing | 0.177 | Increase |
D144A | 648 | −1.411 | Destabilizing | 0.415 | Increase |
S166G | 158 | 1.416 | Stabilizing | 0.225 | Increase |
Stability | Frequency |
---|---|
Destabilizing | 529 |
Stabilizing | 404 |
Total | 933 |
Flexibility | |
Decrease | 391 |
Increase | 542 |
Total | 933 |
S. NO | Mutation | Frequency | * ΔΔG: kcal/mol | Stability |
---|---|---|---|---|
1. | V121F | 14 | −0.463 | Destabilizing |
2. | V121A | 1 | −2.194 | Destabilizing |
3. | V121D | 1 | −1.469 | Destabilizing |
4. | V121I | 13 | 0.375 | Stabilizing |
5. | V121P | 1 | −1.847 | Destabilizing |
6. | V121W | 1 | 1.136 | Stabilizing |
7. | L122I | 3 | 0.184 | Stabilizing |
8. | L122V | 2 | −2.541 | Destabilizing |
9. | L122F | 21 | −0.577 | Destabilizing |
10. | L122P | 1 | −1.106 | Destabilizing |
11. | L122R | 1 | −0.788 | Destabilizing |
12. | L123F | 14 | −0.784 | Destabilizing |
13. | L123W | 1 | −1.189 | Destabilizing |
14. | L123E | 1 | −2.835 | Destabilizing |
15. | L123I | 1 | −0.175 | Destabilizing |
16. | R124C | 126 | −1.116 | Destabilizing |
17. | R124H | 3 | −0.34 | Destabilizing |
18. | R124V | 2 | −0.096 | Destabilizing |
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Mou, K.; Mukhtar, F.; Khan, M.T.; Darwish, D.B.; Peng, S.; Muhammad, S.; Al-Sehemi, A.G.; Wei, D.-Q. Emerging Mutations in Nsp1 of SARS-CoV-2 and Their Effect on the Structural Stability. Pathogens 2021, 10, 1285. https://doi.org/10.3390/pathogens10101285
Mou K, Mukhtar F, Khan MT, Darwish DB, Peng S, Muhammad S, Al-Sehemi AG, Wei D-Q. Emerging Mutations in Nsp1 of SARS-CoV-2 and Their Effect on the Structural Stability. Pathogens. 2021; 10(10):1285. https://doi.org/10.3390/pathogens10101285
Chicago/Turabian StyleMou, Kejie, Farwa Mukhtar, Muhammad Tahir Khan, Doaa B. Darwish, Shaoliang Peng, Shabbir Muhammad, Abdullah G. Al-Sehemi, and Dong-Qing Wei. 2021. "Emerging Mutations in Nsp1 of SARS-CoV-2 and Their Effect on the Structural Stability" Pathogens 10, no. 10: 1285. https://doi.org/10.3390/pathogens10101285