Skip to main content

Advertisement

SpringerLink
Log in

SARS-CoV-2: analysis of the effects of mutations in non-structural proteins

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

A worldwide pandemic that started in China in late 2019 was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded RNA virus belonging to the family Coronaviridae. Due to its structural variability and mutability, this virus continues to evolve and pose a major health threat around the world. Its characteristics, such as transmissibility, antigenicity, and resistance to drugs and vaccines, are continually altered through mutations. Examining mutational hotspots and their structural repercussions can thus aid in the development of more-effective vaccinations and treatment plans. In this study, we used full genome sequences of SARS-CoV-2 variants to predict structural changes in viral proteins. These sequences were obtained from the Global Initiative on Sharing Avian Influenza Data (GISAID), and a set of significant mutations were identified in each of the non-structural proteins (NSP1-16) and structural proteins, including the envelope, nucleocapsid, membrane, and spike proteins. The mutations were characterized as stabilizing or destabilizing based on their effect on protein dynamics and stability, and their impact on structure and function was evaluated. Among all of the proteins, NSP6 stands out as especially variable. The results of this study augment our understanding of how mutational events influence virus pathogenicity and evolution.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

Data availability

The data that support the findings of this study are provided in the supplementary information.

References

  1. Lam WK, Zhong NS, Tan WC (2003) Overview on SARS in Asia and the World. Respirology 8(S2). https://doi.org/10.1046/J.1440-1843.2003.00516.X

  2. Memish ZA, Perlman S, Van Kerkhove MD, Zumla A (2020) Middle East Respiratory Syndrome. Lancet 395:1063–1077. https://doi.org/10.1016/S0140-6736(19)33221-0

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Alimohamadi Y, Tola HH, Abbasi-Ghahramanloo A, Janani M, Sepandi M (2021) Case Fatality Rate of COVID-19: A Systematic Review and Meta-Analysis. J Prev Med Hyg 62:E311. https://doi.org/10.15167/2421-4248/JPMH2021.62.2.1627

    Article  PubMed Central  PubMed  Google Scholar 

  4. Wang LF, Eaton BT, Bats (2007) Civets and the Emergence of SARS. Curr Top Microbiol Immunol 315:325–344. https://doi.org/10.1007/978-3-540-70962-6_13

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Memish ZA, Mishra N, Olival KJ, Fagbo SF, Kapoor V, Epstein JH, AlHakeem R; al, Asmari M, Islam A, Kapoor A et al (2013) Middle East Respiratory Syndrome Coronavirus in Bats, Saudi Arabia. Emerg Infect Dis 19. https://doi.org/10.3201/EID1911.131172

  6. Hemida MG, Chu DKW, Poon LLM, Perera RAPM, Alhammadi MA, Ng HY, Siu LY, Guan Y, Alnaeem A, Peiris M (2014) MERS Coronavirus in Dromedary Camel Herd, Saudi Arabia. Emerg Infect Dis 20. https://doi.org/10.3201/EID2007.140571

  7. Chen F, Cao S, Xin J, Luo X (2013) Ten Years after SARS: Where Was the Virus From? J Thorac Dis 5. https://doi.org/10.3978/J.ISSN.2072-1439.2013.06.09

  8. Weiss SR, Navas-Martin S (2005) Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus. Microbiol Mol Biol Rev 69:635. https://doi.org/10.1128/MMBR.69.4.635-664.2005

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Pustake M, Tambolkar I, Giri P, Gandhi CSARS (2022) MERS and CoVID-19: An Overview and Comparison of Clinical, Laboratory and Radiological Features. J Family Med Prim Care 11(10). https://doi.org/10.4103/JFMPC.JFMPC_839_21

  10. Wu S, Tian C, Liu P, Guo D, Zheng W, Huang X, Zhang Y, Liu L (2021) Effects of SARS-CoV-2 Mutations on Protein Structures and Intraviral Protein-Protein Interactions. J Med Virol 93:2132–2140. https://doi.org/10.1002/JMV.26597

    Article  CAS  PubMed  Google Scholar 

  11. Thakur S, Sasi S, Pillai SG, Nag A, Shukla D, Singhal R, Phalke S, Velu GS (2022) .K. SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines. Front Med (Lausanne) 9. https://doi.org/10.3389/FMED.2022.815389/BIBTEX

  12. Tracking SARS- (2023) CoV-2 Variants Available online: https://doi.org/https://www.who.int/activities/tracking-SARS-CoV-2-variants (accessed on 21

  13. Abavisani M, Rahimian K, Mahdavi B, Tokhanbigli S, Mollapour Siasakht M, Farhadi A, Kodori M, Mahmanzar M, Meshkat Z (2022) Mutations in SARS-CoV-2 Structural Proteins: A Global Analysis. Virol J 19:1–19. https://doi.org/10.1186/S12985-022-01951-7/FIGURES/12

    Article  Google Scholar 

  14. Konishi T (2022) Mutations in SARS-CoV-2 Are on the Increase against the Acquired Immunity. PLoS ONE 17:e0271305. https://doi.org/10.1371/JOURNAL.PONE.0271305

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Abavisani M, Rahimian K, Mahdavi B, Tokhanbigli S, Mollapour Siasakht M, Farhadi A, Kodori M, Mahmanzar M, Meshkat Z (2022) Mutations in SARS-CoV-2 Structural Proteins: A Global Analysis. Virol J 19:1–19. https://doi.org/10.1186/S12985-022-01951-7/FIGURES/12

    Article  Google Scholar 

  16. 2022 Medical Device Recalls | FDA Available online (2023) : https://www.fda.gov/medical-devices/medical-device-recalls/2022-medical-device-recalls (accessed on 21)

  17. Wang R, Chen J, Gao K, Hozumi Y, Yin C, Wei GW (2021) Analysis of SARS-CoV-2 Mutations in the United States Suggests Presence of Four Substrains and Novel Variants. Communications Biology 2021 4:1 4, 1–14, doi:https://doi.org/10.1038/s42003-021-01754-6

  18. Banoun H (2021) Evolution of SARS-CoV-2: Review of Mutations, Role of the Host Immune System. Nephron 145:392–403. https://doi.org/10.1159/000515417

    Article  CAS  PubMed  Google Scholar 

  19. Wang R, Chen J, Hozumi Y, Yin C, Wei GW (2022) Emerging Vaccine-Breakthrough SARS-CoV-2 Variants. ACS Infect Dis 8:546–556. https://doi.org/10.1021/ACSINFECDIS.1C00557/SUPPL_FILE/ID1C00557_SI_002.PDF.

    Article  CAS  PubMed  Google Scholar 

  20. Zhou W, Xu C, Wang P, Luo M, Xu Z, Cheng R, Jin X, Guo Y, Xue G, Juan L et al (2021) N439K Variant in Spike Protein Alter the Infection Efficiency and Antigenicity of SARS-CoV-2 Based on Molecular Dynamics Simulation. Front Cell Dev Biol 9:2071. https://doi.org/10.3389/FCELL.2021.697035/BIBTEX

    Article  Google Scholar 

  21. Thomson EC, Rosen LE, Shepherd JG, Spreafico R, da Silva Filipe A, Wojcechowskyj JA, Davis C, Piccoli L, Pascall DJ, Dillen J et al (2021) Circulating SARS-CoV-2 Spike N439K Variants Maintain Fitness While Evading Antibody-Mediated Immunity. Cell 184:1171–1187e20. https://doi.org/10.1016/J.CELL.2021.01.037

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Abavisani M, Rahimian K, Mahdavi B, Tokhanbigli S, Mollapour Siasakht M, Farhadi A, Kodori M, Mahmanzar M, Meshkat Z (2022) Mutations in SARS-CoV-2 Structural Proteins: A Global Analysis. Virol J 19:220. https://doi.org/10.1186/S12985-022-01951-7

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Emerging Variants of SARS-CoV-2 And Novel Therapeutics Against Coronavirus (COVID-19) (2023) - PubMed Available online: https://pubmed.ncbi.nlm.nih.gov/34033342/ (accessed on 16

  24. A COVID Treatment Wanes (2023) : New Variants Outsmart Most Monoclonal Antibodies: Shots - Health News : NPR Available online: https://www.npr.org/sections/health-shots/2022/11/20/1137892932/monoclonal-antibodies-covid-treatment (accessed on 16

  25. da Costa CHS, de Freitas CAB, Alves CN, Lameira J (2022) Assessment of Mutations on RBD in the Spike Protein of SARS-CoV-2 Alpha, Delta and Omicron Variants. Scientific Reports 2022 12:1 12, 1–10, doi:https://doi.org/10.1038/s41598-022-12479-9

  26. Klinakis A, Cournia Z, Rampias T (2021) N-Terminal Domain Mutations of the Spike Protein Are Structurally Implicated in Epitope Recognition in Emerging SARS-CoV-2 Strains. Comput Struct Biotechnol J 19:5556–5567. https://doi.org/10.1016/J.CSBJ.2021.10.004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Harvey WT, Carabelli AM, Jackson B, Gupta RK, Thomson EC, Harrison EM, Ludden C, Reeve R, Rambaut A, Peacock SJ et al (2021) SARS-CoV-2 Variants, Spike Mutations and Immune Escape. Nature Reviews Microbiology 2021 19:7 19, 409–424, doi:https://doi.org/10.1038/s41579-021-00573-0

  28. Dynamut | Prediction Submission Available online : https://biosig.lab.uq.edu.au/dynamut/prediction (accessed on 17 February 2023)

  29. Rodrigues CHM, Pires DEV, Ascher DB, DynaMut (2018) Predicting the Impact of Mutations on Protein Conformation, Flexibility and Stability. Nucleic Acids Res 46:W350–W355. https://doi.org/10.1093/NAR/GKY300

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Rodrigues CHM, Pires DEV, Ascher DB (2021) DynaMut2: Assessing Changes in Stability and Flexibility upon Single and Multiple Point Missense Mutations. Protein Sci 30:60–69. https://doi.org/10.1002/PRO.3942

    Article  CAS  PubMed  Google Scholar 

  31. R 4.1.1 Available online: http://www.npackd.org/p/r/4.1.1 (accessed on 2 March 2023)

  32. Rodrigues CHM, Pires DEV, Ascher DB, DynaMut (2018) Predicting the Impact of Mutations on Protein Conformation, Flexibility and Stability. Nucleic Acids Res 46:W350–W355. https://doi.org/10.1093/NAR/GKY300

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Grant BJ, Rodrigues APC, ElSawy KM, McCammon JA, Caves LSD (2006) Bio3d: An R Package for the Comparative Analysis of Protein Structures. Bioinformatics 22:2695–2696. https://doi.org/10.1093/BIOINFORMATICS/BTL461

    Article  CAS  PubMed  Google Scholar 

  34. Frappier V, Najmanovich RJA, Coarse-Grained (2014) Elastic Network Atom Contact Model and Its Use in the Simulation of Protein Dynamics and the Prediction of the Effect of Mutations. PLoS Comput Biol 10:e1003569. https://doi.org/10.1371/JOURNAL.PCBI.1003569

    Article  PubMed Central  PubMed  Google Scholar 

  35. UCSF Chimera Home Page Available online (2023) : https://www.cgl.ucsf.edu/chimera/ (accessed on 17

  36. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera—A Visualization System for Exploratory Research and Analysis. J Comput Chem 25:1605–1612. https://doi.org/10.1002/JCC.20084

    Article  CAS  PubMed  Google Scholar 

  37. Benvenuto D, Angeletti S, Giovanetti M, Bianchi M, Pascarella S, Cauda R, Ciccozzi M, Cassone A (2020) Evolutionary Analysis of SARS-CoV-2: How Mutation of Non-Structural Protein 6 (NSP6) Could Affect Viral Autophagy. J Infect 81:e24–e27. https://doi.org/10.1016/J.JINF.2020.03.058

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. González-Vázquez LD, Arenas M (2023) Molecular Evolution of SARS-CoV-2 during the COVID-19 Pandemic. Genes (Basel) 14. https://doi.org/10.3390/GENES14020407

  39. Kistler KE, Huddleston J, Bedford T (2022) Rapid and Parallel Adaptive Mutations in Spike S1 Drive Clade Success in SARS-CoV-2. Cell Host Microbe 30:545. https://doi.org/10.1016/J.CHOM.2022.03.018

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Khan MT, Zeb MT, Ahsan H, Ahmed A, Ali A, Akhtar K, Malik SI, Cui Z, Ali S, Khan AS et al (2021) SARS-CoV-2 Nucleocapsid and Nsp3 Binding: An in Silico Study. Arch Microbiol 203:59–66. https://doi.org/10.1007/S00203-020-01998-6/FIGURES/3

    Article  CAS  PubMed  Google Scholar 

  41. Zhou Y, Liu Y, Gupta S, Paramo MI, Hou Y, Mao C, Luo Y, Judd J, Wierbowski S, Bertolotti M et al (2022) A Comprehensive SARS-CoV-2–Human Protein–Protein Interactome Reveals COVID-19 Pathobiology and Potential Host Therapeutic Targets. Nature Biotechnology 2022 41:1 41, 128–139, doi:https://doi.org/10.1038/s41587-022-01474-0

  42. Ou J, Lan W, Wu X, Zhao T, Duan B, Yang P, Ren Y, Quan L, Zhao W, Seto D et al (2022) Tracking SARS-CoV-2 Omicron Diverse Spike Gene Mutations Identifies Multiple Inter-Variant Recombination Events. Signal Transduction and Targeted Therapy 2022, 7, 1–9, doi:https://doi.org/10.1038/s41392-022-00992-2

  43. Zhang L, Jackson CB, Mou H, Ojha A, Peng H, Quinlan BD, Rangarajan ES, Pan A, Vanderheiden A, Suthar MS et al (2020) SARS-CoV-2 Spike-Protein D614G Mutation Increases Virion Spike Density and Infectivity. Nature Communications 2020 11:1 11, 1–9, doi:https://doi.org/10.1038/s41467-020-19808-4

  44. Plante JA, Liu Y, Liu J, Xia H, Johnson BA, Lokugamage KG, Zhang X, Muruato AE, Zou J, Fontes-Garfias CR et al (2020) Spike Mutation D614G Alters SARS-CoV-2 Fitness. Nature 2020 592:7852 592, 116–121, doi:https://doi.org/10.1038/s41586-020-2895-3

  45. Letarov Av, Babenko Vv, Kulikov EE, Free (2021) SARS-CoV-2 Spike Protein S1 Particles May Play a Role in the Pathogenesis of COVID-19 Infection. Biochem (Mosc) 86:257. https://doi.org/10.1134/S0006297921030032

    Article  CAS  Google Scholar 

  46. Xia B, Wang Y, Pan X, Cheng X, Ji H, Zuo X, Jiang H, Li J, Gao Z (2022) Why Is the SARS-CoV-2 Omicron Variant Milder? The Innovation 3:100251. https://doi.org/10.1016/J.XINN.2022.100251

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Ruan Y, Hou M, Tang X, He X, Lu X, Lu J, Wu CI, Wen H (2022) The Runaway Evolution of SARS-CoV-2 Leading to the Highly Evolved Delta Strain. Mol Biol Evol 39. https://doi.org/10.1093/MOLBEV/MSAC046

  48. Yuan S, Peng L, Park JJ, Hu Y, Devarkar SC, Dong MB, Shen Q, Wu S, Chen S, Lomakin IB et al (2020) Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA. Mol Cell 80:1055–1066e6. https://doi.org/10.1016/J.MOLCEL.2020.10.034

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Ghaleh SS, Rahimian K, Mahmanzar M, Mahdavi B, Tokhanbigli S, Sisakht MM, Farhadi A, Bakhtiari MM, Kuehu DL, Deng Y (2022) SARS-CoV-2 Non-Structural Protein 1(NSP1) Mutation Virulence and Natural Selection: Evolutionary Trends in the Six Continents. Virus Res 323:199016–199016. https://doi.org/10.1016/J.VIRUSRES.2022.199016

    Article  PubMed Central  PubMed  Google Scholar 

  50. Semper C, Watanabe N, Savchenko A (2021) Structural Characterization of Nonstructural Protein 1 from SARS-CoV-2. iScience 24, doi:https://doi.org/10.1016/J.ISCI.2020.101903

  51. Thoms M, Buschauer R, Ameismeier M, Koepke L, Denk T, Hirschenberger M, Kratzat H, Hayn M, MacKens-Kiani T, Cheng J et al (2020) Structural Basis for Translational Shutdown and Immune Evasion by the Nsp1 Protein of SARS-CoV-2. Science 369:1249–1256. https://doi.org/10.1126/SCIENCE.ABC8665

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Schubert K, Karousis ED, Jomaa A, Scaiola A, Echeverria B, Gurzeler LA, Leibundgut M, Thiel V, Mühlemann O, Ban N (2020) SARS-CoV-2 Nsp1 Binds the Ribosomal MRNA Channel to Inhibit Translation. Nature Structural & Molecular Biology 2020, 27, 959–966, doi:https://doi.org/10.1038/s41594-020-0511-8

  53. Wang Y, Kirkpatrick J, Lage S, Carlomagno T (2023) Structural Insights into the Activity Regulation of Full-Length Non-Structural Protein 1 from SARS-CoV-2. Structure 31, 128–137.e5, doi:https://doi.org/10.1016/J.STR.2022.12.006

  54. Mou K, Mukhtar F, Khan MT, Darwish DB, Peng S, Muhammad S, Al-Sehemi AG, Wei DQ (2021) Emerging Mutations in Nsp1 of Sars-Cov-2 and Their Effect on the Structural Stability. Pathogens 10, doi:https://doi.org/10.3390/PATHOGENS10101285/S1

  55. Xu Z, Choi JH, Dai DL, Luo J, Ladak RJ, Li Q, Wang Y, Zhang C, Wiebe S, Liu ACH et al (2022) SARS-CoV-2 Impairs Interferon Production via NSP2-Induced Repression of MRNA Translation. Proc Natl Acad Sci U S A 119. https://doi.org/10.1073/PNAS.2204539119/-/DCSUPPLEMENTAL

  56. Cornillez-Ty CT, Liao L, John R, Yates I, Kuhn P, Buchmeier MJ (2009) Severe Acute Respiratory Syndrome Coronavirus Nonstructural Protein 2 Interacts with a Host Protein Complex Involved in Mitochondrial Biogenesis and Intracellular Signaling. J Virol 83:10314. https://doi.org/10.1128/JVI.00842-09

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Madej T, Lanczycki CJ, Zhang D, Thiessen PA, Geer RC, Marchler-Bauer A, Bryant SH (2014) MMDB and VAST+: Tracking Structural Similarities between Macromolecular Complexes. Nucleic Acids Res 42. https://doi.org/10.1093/NAR/GKT1208

  58. Gupta M, Azumaya CM, Moritz M, Pourmal S, Diallo A, Merz GE, Jang G, Bouhaddou M, Fossati A, Brilot AF et al (2021) CryoEM and AI Reveal a Structure of SARS-CoV-2 Nsp2, a Multifunctional Protein Involved in Key Host Processes. Res Sq. https://doi.org/10.21203/RS.3.RS-515215/V1

    Article  PubMed Central  PubMed  Google Scholar 

  59. Gupta M, Azumaya CM, Moritz M, Pourmal S, Diallo A, Merz GE, Jang G, Bouhaddou M, Fossati A, Brilot AF et al (2021) CryoEM and AI Reveal a Structure of SARS-CoV-2 Nsp2, a Multifunctional Protein Involved in Key Host Processes. bioRxiv doi:https://doi.org/10.1101/2021.05.10.443524

  60. Yoshimoto FK (2020) The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19. Protein J 39:198. https://doi.org/10.1007/S10930-020-09901-4

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Sakai Y, Kawachi K, Terada Y, Omori H, Matsuura Y, Kamitani W (2017) Two-Amino Acids Change in the Nsp4 of SARS Coronavirus Abolishes Viral Replication. Virology 510:165–174. https://doi.org/10.1016/J.VIROL.2017.07.019

    Article  CAS  PubMed  Google Scholar 

  62. Computational Predictions of Protein Structures Associated with COVID-19 Available online: https://www.deepmind.com/open-source/computational-predictions-of-protein-structures-associated-with-covid-19 (accessed on 2 March 2023)

  63. Tunyasuvunakool K, Adler J, Wu Z, Green T, Zielinski M, Žídek A, Bridgland A, Cowie A, Meyer C, Laydon A et al (2021) Highly Accurate Protein Structure Prediction for the Human Proteome. Nature 2021 596:7873 596, 590–596, doi:https://doi.org/10.1038/s41586-021-03828-1

  64. SARS-CoV-2 Protein NSP4 - Proteopedia, Life in 3D Available online: https://proteopedia.org/wiki/index.php/SARS-CoV-2_protein_NSP4 (accessed on 17 February 2023)

  65. Modeling of the SARS-COV-2 Genome Using D-I-TASSER Available online : https://zhanggroup.org/COVID-19/ (accessed on 17 February 2023).

  66. Lavigne M, Helynck O, Rigolet P, Boudria-Souilah R, Nowakowski M, Baron B, Brülé S, Hoos S, Raynal B, Guittat L et al (2021) SARS-CoV-2 Nsp3 Unique Domain SUD Interacts with Guanine Quadruplexes and G4-Ligands Inhibit This Interaction. Nucleic Acids Res 49:7695–7712. https://doi.org/10.1093/NAR/GKAB571

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Tao X, Zhang L, Du L, Lu K, Zhao Z, Xie Y, Li X, Huang S, Wang PH, Pan JA et al (2022) Inhibition of SARS-CoV-2 Replication by Zinc Gluconate in Combination with Hinokitiol. J Inorg Biochem 231:111777. https://doi.org/10.1016/J.JINORGBIO.2022.111777

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Yadav R, Chaudhary JK, Jain N, Chaudhary PK, Khanra S, Dhamija P, Sharma A, Kumar A, Handu S (2021) Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19. Cells 10:821. https://doi.org/10.3390/CELLS10040821

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Dai W, Zhang B, Jiang XM, Su H, Li J, Zhao Y, Xie X, Jin Z, Peng J, Liu F et al (2020) Structure-Based Design of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease. Science 368:1331–1335. https://doi.org/10.1126/SCIENCE.ABB4489

    Article  CAS  PubMed  Google Scholar 

  70. Planès R, Pinilla M, Santoni K, Hessel A, Passemar C, Lay K, Paillette P, Valadão ALC, Robinson KS, Bastard P et al (2022) Human NLRP1 Is a Sensor of Pathogenic Coronavirus 3CL Proteases in Lung Epithelial Cells. Mol Cell 82:2385. https://doi.org/10.1016/J.MOLCEL.2022.04.033

    Article  PubMed Central  PubMed  Google Scholar 

  71. Yashvardhini N, Kumar A, Jha DK (2022) Analysis of SARS-CoV-2 Mutations in the Main Viral Protease (NSP5) and Its Implications on the Vaccine Designing Strategies. Vacunas 23, S1, doi:https://doi.org/10.1016/J.VACUN.2021.10.002

  72. Sacco MD, Hu Y, Gongora MV, Meilleur F, Kemp MT, Zhang X, Wang J, Chen Y (2022) The P132H Mutation in the Main Protease of Omicron SARS-CoV-2 Decreases Thermal Stability without Compromising Catalysis or Small-Molecule Drug Inhibition. Cell Res 32:498–500. https://doi.org/10.1038/S41422-022-00640-Y

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Lin X, Sha Z, Trimpert J, Kunec D, Jiang C, Xiong Y, Xu B, Zhu Z, Xue W, Wu H (2023) T492I Mutation Alters SARS-CoV-2 Properties via Modulating Viral Non-Structural Proteins. bioRxiv 2023.01.15.524090, https://doi.org/10.1101/2023.01.15.524090

  74. Okamoto Y (1994) Helix-Forming Tendencies of Nonpolar Amino Acids Predicted by Monte Carlo Simulated Annealing. Proteins 19:14–23. https://doi.org/10.1002/PROT.340190104

    Article  CAS  PubMed  Google Scholar 

  75. Zheng W, Zhang C, Li Y, Pearce R, Bell EW, Zhang Y (2021) Folding Non-Homologous Proteins by Coupling Deep-Learning Contact Maps with I-TASSER Assembly Simulations. Cell Rep methods 1. https://doi.org/10.1016/J.CRMETH.2021.100014

  76. SARS-CoV-2 Protein NSP6 - Proteopedia, Life in 3D Available online: https://proteopedia.org/wiki/index.php/SARS-CoV-2_protein_NSP6 (accessed on 17 February 2023)

  77. Kumar S, Javed R, Mudd M, Pallikkuth S, Lidke KA, Jain A, Tangavelou K, Gudmundsson SR, Ye C, Rusten TE et al (2021) Mammalian Hybrid Pre-Autophagosomal Structure HyPAS Generates Autophagosomes. Cell 184:5950–5969e22. https://doi.org/10.1016/J.CELL.2021.10.017

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Ricciardi S, Guarino AM, Giaquinto L, Polishchuk Ev, Santoro M, di Tullio G, Wilson C, Panariello F, Soares VC, Dias SSG et al (2022) The Role of NSP6 in the Biogenesis of the SARS-CoV-2 Replication Organelle. Nature 2022 606:7915 606, 761–768, doi:https://doi.org/10.1038/s41586-022-04835-6

  79. Ricciardi S, Guarino AM, Giaquinto L, Polishchuk Ev, Santoro M, di Tullio G, Wilson C, Panariello F, Soares VC, Dias SSG et al (2022) The Role of NSP6 in the Biogenesis of the SARS-CoV-2 Replication Organelle. Nature 606:761–768. https://doi.org/10.1038/S41586-022-04835-6

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Xia H, Cao Z, Xie X, Zhang X, Chen JYC, Wang H, Menachery VD, Rajsbaum R, Shi PY (2020) Evasion of Type I Interferon by SARS-CoV-2. Cell Rep 33. https://doi.org/10.1016/J.CELREP.2020.108234

  81. Banerjee AK, Blanco MR, Bruce EA, Honson DD, Chen LM, Chow A, Bhat P, Ollikainen N, Quinodoz SA, Loney C et al (2020) SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses. Cell 183:1325–1339e21. https://doi.org/10.1016/j.cell.2020.10.004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Zhang C, Chen Y, Li L, Yang Y, He J, Chen C, Su D (2020) Structural Basis for the Multimerization of Nonstructural Protein Nsp9 from SARS-CoV-2. Mol Biomed 1:1–9. https://doi.org/10.1186/S43556-020-00005-0/TABLES/1

    Article  Google Scholar 

  83. de Araújo O, Pinheiro J, Zamora S, Alves WJ, Lameira CN, Lima J, Structural AH (2021) Energetic and Lipophilic Analysis of SARS-CoV-2 Non-Structural Protein 9 (NSP9). Sci Rep 11. https://doi.org/10.1038/S41598-021-02366-0

  84. Newman JA, Douangamath A, Yadzani S, Yosaatmadja Y, Aimon A, Brandão-Neto J, Dunnett L, Gorrie-stone T, Skyner R, Fearon D et al (2021) Structure, Mechanism and Crystallographic Fragment Screening of the SARS-CoV-2 NSP13 Helicase. Nat Commun 12:4848–4848. https://doi.org/10.1038/S41467-021-25166-6

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Rashid F, Suleman M, Shah A, Dzakah EE, Chen S, Wang H, Tang S (2021) Structural Analysis on the Severe Acute Respiratory Syndrome Coronavirus 2 Non-Structural Protein 13 Mutants Revealed Altered Bonding Network With TANK Binding Kinase 1 to Evade Host Immune System. Front Microbiol 12:3575. https://doi.org/10.3389/FMICB.2021.789062/BIBTEX

    Article  Google Scholar 

  86. Cao C, He L, Tian Y, Qin Y, Sun H, Ding W, Gui L, Wu P (2021) Molecular Epidemiology Analysis of Early Variants of SARS-CoV-2 Reveals the Potential Impact of Mutations P504L and Y541C (NSP13) in the Clinical COVID-19 Outcomes. Infect Genet Evol 92. https://doi.org/10.1016/J.MEEGID.2021.104831

  87. Pillon MC, Frazier MN, Dillard LB, Williams JG, Kocaman S, Krahn JM, Perera L, Hayne CK, Gordon J, Stewart ZD et al (2021) Cryo-EM Structures of the SARS-CoV-2 Endoribonuclease Nsp15 Reveal Insight into Nuclease Specificity and Dynamics. Nat Commun 12. https://doi.org/10.1038/S41467-020-20608-Z

  88. Hackbart M, Deng X, Baker SC (2020) Coronavirus Endoribonuclease Targets Viral Polyuridine Sequences to Evade Activating Host Sensors. Proc Natl Acad Sci U S A 117:8094–8103. https://doi.org/10.1073/PNAS.1921485117/SUPPL_FILE/PNAS.1921485117.SAPP.PDF

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Yoshimoto FK (2020) The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19. Protein J 39:198–216. https://doi.org/10.1007/S10930-020-09901-4/FIGURES/1

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Kim Y, Jedrzejczak R, Maltseva NI, Wilamowski M, Endres M, Godzik A, Michalska K, Joachimiak A (2020) Crystal Structure of Nsp15 Endoribonuclease NendoU from SARS-CoV-2. Protein Sci 29:1596–1605. https://doi.org/10.1002/PRO.3873

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  91. Kim Y, Jedrzejczak R, Maltseva NI, Wilamowski M, Endres M, Godzik A, Michalska K, Joachimiak A (2020) Crystal Structure of Nsp15 Endoribonuclease NendoU from SARS-CoV‐2. Protein Sci 29:1596. https://doi.org/10.1002/PRO.3873

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  92. Yin W, Mao C, Luan X, Shen DD, Shen Q, Su H, Wang X, Zhou F, Zhao W, Gao M et al (2020) Structural Basis for Inhibition of the RNA-Dependent RNA Polymerase from SARS-CoV-2 by Remdesivir. Sci (1979) 368:1499–1504. https://doi.org/10.1126/SCIENCE.ABC1560/SUPPL_FILE/ABC1560_YIN_SM_CORRECTED.PDF

    Article  CAS  Google Scholar 

  93. Hillen HS, Kokic G, Farnung L, Dienemann C, Tegunov D, Cramer P (2020) Structure of Replicating SARS-CoV-2 Polymerase. Nature 2020 584:7819 584, 154–156, doi:https://doi.org/10.1038/s41586-020-2368-8

  94. Ramaswamy K, Rashid M, Ramasamy S, Jayavelu T, Venkataraman S (2022) Revisiting Viral RNA-Dependent RNA Polymerases: Insights from Recent Structural Studies. Viruses 2022 14:2200. https://doi.org/10.3390/V14102200

    Article  CAS  Google Scholar 

  95. Venkataraman S, Prasad BVLS, Selvarajan RRNA, Dependent RNA (2018) Polymerases: Insights from Structure, Function and Evolution. Viruses 10, doi:https://doi.org/10.3390/V10020076

  96. Showers WM, Leach SM, Kechris K, Strong M (2022) Longitudinal Analysis of SARS-CoV-2 Spike and RNA-Dependent RNA Polymerase Protein Sequences Reveals the Emergence and Geographic Distribution of Diverse Mutations. Infect Genet Evol 97. https://doi.org/10.1016/J.MEEGID.2021.105153

  97. Yin W, Mao C, Luan X, Shen DD, Shen Q, Su H, Wang X, Zhou F, Zhao W, Gao M et al (2020) Structural Basis for Inhibition of the RNA-Dependent RNA Polymerase from SARS-CoV-2 by Remdesivir. Science 368:1499–1504. https://doi.org/10.1126/SCIENCE.ABC1560

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. Ilmjärv S, Abdul F, Acosta-Gutiérrez S, Estarellas C, Galdadas I, Casimir M, Alessandrini M, Gervasio FL, Krause KH (2021) Concurrent Mutations in RNA-Dependent RNA Polymerase and Spike Protein Emerged as the Epidemiologically Most Successful SARS-CoV-2 Variant. Scientific Reports 2021, 11, 1–13, doi:https://doi.org/10.1038/s41598-021-91662-w

  99. Petersen E, Koopmans M, Go U, Hamer DH, Petrosillo N, Castelli F, Storgaard M; al, Khalili S, Simonsen L (2020) Comparing SARS-CoV-2 with SARS-CoV and Influenza Pandemics. Lancet Infect Dis 20:e238–e244. https://doi.org/10.1016/S1473-3099(20)30484-9

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  100. Joseph JS, Saikatendu KS, Subramanian V, Neuman BW, Brooun A, Griffith M, Moy K, Yadav MK, Velasquez J, Buchmeier MJ et al (2006) Crystal Structure of Nonstructural Protein 10 from the Severe Acute Respiratory Syndrome Coronavirus Reveals a Novel Fold with Two Zinc-Binding Motifs. J Virol 80:7894. https://doi.org/10.1128/JVI.00467-06

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Lin S, Chen H, Chen Z, Yang F, Ye F, Zheng Y, Yang J, Lin X, Sun H, Wang L et al (2021) Crystal Structure of SARS-CoV-2 Nsp10 Bound to Nsp14-ExoN Domain Reveals an Exoribonuclease with Both Structural and Functional Integrity. Nucleic Acids Res 49:5382–5392. https://doi.org/10.1093/NAR/GKAB320

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  102. Sarma H, Sastry GN (2022) A Computational Study on the Interaction of NSP10 and NSP14: Unraveling the RNA Synthesis Proofreading Mechanism in SARS-CoV-2, SARS-CoV, and MERS-CoV. ACS Omega 7:29995–30014. https://doi.org/10.1021/ACSOMEGA.2C03007/SUPPL_FILE/AO2C03007_SI_001.PDF

    Article  CAS  PubMed Central  Google Scholar 

  103. Lin S, Chen H, Chen Z, Yang F, Ye F, Zheng Y, Yang J, Lin X, Sun H, Wang L et al (2021) Crystal Structure of SARS-CoV-2 Nsp10 Bound to Nsp14-ExoN Domain Reveals an Exoribonuclease with Both Structural and Functional Integrity. Nucleic Acids Res 49:5382. https://doi.org/10.1093/NAR/GKAB320

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgement

SV thanks the University Grants Commission-Faculty Recharge Program (UGC-FRP), New Delhi, India, for financial support. The authors thank BIC at DoBT, AU (BT/PR40163/BTIS/137/31/2021), DBT, Govt. of India, for computational facilities.

Author information

Authors and Affiliations

  1. Department of Biotechnology, Anna University, 600025, Guindy, Chennai, Tamil Nādu, India

    Kavya Senthilazhagan, Seshagiri Sakthimani, Deepthi Kallanja & Sangita Venkataraman

Authors
  1. Kavya Senthilazhagan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seshagiri Sakthimani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Deepthi Kallanja
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sangita Venkataraman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

KS and SS were involved in data analysis and manuscript writing, while DK generated the mutational data. SV was involved in conceptualization, analysis, and writing of the manuscript.

Corresponding author

Correspondence to Sangita Venkataraman.

Ethics declarations

Conflict of interest

None

Declarations

Dr. Sangita Venkataraman receives her salary from University Grants Commission-Faculty Recharge Program (UGC-FRP), New Delhi. The work was not funded by any funding agency.

Additional information

Communicated by Sheela Ramamoorthy

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Below is the link to the electronic supplementary material

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Senthilazhagan, K., Sakthimani, S., Kallanja, D. et al. SARS-CoV-2: analysis of the effects of mutations in non-structural proteins. Arch Virol 168, 186 (2023). https://doi.org/10.1007/s00705-023-05818-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00705-023-05818-2

Keywords

Search

Navigation