Document Type : original article


1 Department of Microbiology, Golestan University of Medical Sciences. Gorgan, Iran.

2 Department of Microbiology, Golestan University of Medical Sciences, Gorgan, Iran

3 Senior Scientist, Enterprise-TTM, University of Pittsburgh Medical Center, Pittsburgh, PA

4 Dept. Microbiology. Faculty of Medicine, Golestan University of Medical Sciences


Background: Molecular analysis of SARS-CoV-2 genome is important to predict viral pathogenicity. In addition to transmission, replication is a key factor in pathogenicity of the virus. Notably, mutations in non-structural proteins (NSP3 and NSP12) can affect host immune response and viral replication. Therefore, this study was conducted to investigate different mutations of SARS-CoV-2 NSP3, and NSP12 during different waves of COVID-19 infection.
Methods: We recruited 57 NGS sequences including 8 NGS sequences from Golestan SARS-CoV-2 RNA samples, obtained as part of clinical testing in different referral centers of Iran. After obtaining sequences from the global initiative on sharing all influenza data (GISAID), and evaluating and processing data, all sequences were aligned to the Wuhan variant genome (NC_045512.2) using MEGA6. The HDOCK server was used for molecular docking.
Results: In NSP3, mutations in positions (nts 315, 545, 2666, 3264) were more frequent and among them mutation in positions including nt 545 (aa182) and nt 2666 (aa889) were associated with an increase in codon usage. In the term of NSP12, mutations in positions such as nts 406 (aa137), 965 (aa323), 1233, 1653, 1836, 2733 were more frequent. The molecular docking results showed more affinity in some variants of NSP3 and NSP12 as well.
Conclusion: This study has assessed mutation in SARS-CoV-2 Nsp3, and NSP12 which are viral protease, and viral polymerase (RdRp). The mutations reported in this study may help this virus to replicate faster and evade the pharmaceutical agents which target viral polymerase activity and be very effective in viral pathogenesis. In addition, this study highlights the importance of ongoing genomic variation studies to be performed on SARS-CoV-2 variants.


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