SARS-CoV-2 VOCs, Mutational diversity and clinical outcome: Are they modulating drug efficacy by altered binding strength?
Genomics
; 114(5): 110466, 2022 09.
Article
in English
| MEDLINE | ID: covidwho-2004618
ABSTRACT
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. Mutations, 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
SARS-CoV-2
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Genomics
Journal subject:
Genetics
Year:
2022
Document Type:
Article
Affiliation country:
J.ygeno.2022.110466
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