Wang, Huan; (2023) Structural Dynamics and Bioinformatics Studies of the NSP10 from SARS-CoV-2. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The coronavirus SARS-CoV-2 protects its RNA from being recognized by the host immune responses by methylation of its 5’ end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2’-O-methyltransferase and NSP14 through its N7 methyltransferase activity, which are essential for the replication of the viral genome as well as evading the host's innate immunity. NSP10 acts as a crucial cofactor and stimulator of NSP14 and NSP16. To further understand the role of NSP10, we carried out a comprehensive analysis of >13 million globally collected whole-genome sequences (WGS) of SARS-CoV-2 obtained from the Global Initiative Sharing All Influenza Data (GISAID) and compared it with the reference genome Wuhan/WIV04/2019 to identify all currently known variants in NSP10. T12I, T102I, and A104V in NSP10 have been identified as the three most frequent variants. The dynamic effects of these top variants were studied using well-tempered metadynamics which highlight the limited changes induced by variant evolution in NSP10 and reflect on the critical roles NSP10 plays during the SARS-CoV-2 life cycle. This study also aims to contribute to this growing area of research by exploring the importance and the possible molecular mechanism of NSP10 to the activities of NSP14 and NSP16 by examining the dynamics of NSP10, NSP14, NSP16, NSP10-NSP14 complex, and NSP10-NSP16 complex.

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