OMICRON N501Y MUTATION AMONG SARS-COV-2 LINEAGES: IN SILICO ANALYSIS OF POTENT BINDING TO TYROSINE KINASE AND HYPOTHETICAL REPURPOSED MEDICINE
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Date
2022
Authors
Kazybay, Bexultan
Ahmad, Ashfaq
Mu, Chenglin
Mengdesh, Diana
Xie, Yingqiu
Journal Title
Journal ISSN
Volume Title
Publisher
Travel Medicine and Infectious Disease
Abstract
Variants of SARS-CoV-2 lineages including the most recently circulated Omicron, and previous pandemic
B.1.351, B.1.1.7, which have been public concerns, contain a N501Y mutation located in the spike receptor
binding domain. However, the potential interactions with host cells linking N501Y mutation to pathogenic
relevance remain elusive. Recently, we and others report that kinases such as PI3K/AKT signaling are essential in
SARS-CoV-2 entry. Here we analyzed the predicted potential kinases interacting with the mutation. Bioinformatics
tools including structure-prediction based molecular docking analysis were applied. We found kinases
such as EGFR might potentially act as new factors involving the N501Y mutation binding through possible
phosphorylation at Y501 and enhanced affinity in certain variants. To our surprise, the Omicron receptor binding
domain harboring N501Y mutation did not enhance binding to EGFR which might be due to the mutations of
charged polar to uncharged polar side chains located on the interaction interfaces. Similarly, potent gains of
phosphorylation in B.1.351 and B.1.1.7 by mutations were predicted and interaction networks were analyzed
with enrichment of pathways. Given kinases might be elevated in cancer patients, the N501Y mutation containing
lineages may be possibly much more infectious and additional care for cancer management might be
taken into consideration by precision prevention, therapy or recovery.
Description
Keywords
Type of access: Open Access, N501Y, SARS-CoV-2, EGFR, Network pharmacology
Citation
Kazybay, B., Ahmad, A., Mu, C., Mengdesh, D., & Xie, Y. (2022). Omicron N501Y mutation among SARS-CoV-2 lineages: In silico analysis of potent binding to tyrosine kinase and hypothetical repurposed medicine. Travel Medicine and Infectious Disease, 45, 102242. https://doi.org/10.1016/j.tmaid.2021.102242