期刊
GENOMICS
卷 114, 期 5, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2022.110466
关键词
SARS-CoV-2; Genomic surveillance; Mutation analysis; Disease severity; Molecular docking; Drug efficacy
资金
- Bill and Melinda Gates Foundation (BMGF)
- Foundation for Innovative New Di-agnostics (FIND) [GAP0249]
- AIDS Healthcare Foundation (AHF) [CLP0043]
This study analyzed the genome mutations of SARS-CoV-2 in patients infected with Delta and Omicron variants, and identified significant mutations associated with mortality. The findings suggest that these mutations may affect the binding of Remdesivir and influence disease outcomes.
The global COVID-19 pandemic continues due to emerging Severe Acute Respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC). Here, we performed comprehensive analysis of in-house sequenced SARS-CoV-2 genome mutations dynamics in the patients infected with the VOCs -Delta and Omicron, within Recovered and Mortality patients. Statistical analysis highlighted significant mutations -T4685A, N4992N, and G5063S in RdRp; T19R in NTD spike; K444N and N532H in RBD spike, associated with Delta mortality. Mu-tations, T19I in NTD spike, Q493R and N440K in the RBD spike were significantly associated with Omicron mortality. We performed molecular docking for possible effect of significant mutations on the binding of Remdesivir. We found that Remdesivir showed less binding efficacy with the mutant Spike protein of both Delta and Omicron mortality compared to recovered patients. This indicates that mortality associated mutations could have a modulatory effect on drug binding which could be associated with disease outcome.
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