key: cord-0760045-fpeqryys
authors: Kazybay, Bexultan; Ahmad, Ashfaq; Mu, Chenglin; Mengdesh, Diana; Xie, Yingqiu
title: Omicron N501Y mutation among SARS-CoV-2 lineages: In-silico analysis of potent binding to tyrosine kinase and hypothetical repurposed medicine
date: 2021-12-17
journal: Travel Med Infect Dis
DOI: 10.1016/j.tmaid.2021.102242
sha: 223c626ec202af3037c7d158ae6f83e1d29101ec
doc_id: 760045
cord_uid: fpeqryys

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 is 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 acceptors 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.

mutation located in the spike receptor binding domain. However, the potential interactions 28 with host cells linking N501Y mutation to pathogenic relevance remain elusive. Recently, 29 we and others report that kinases such as PI3K/AKT signaling is essential in SARS-CoV-30 2 entry. Here we analyzed the predicted potential kinases interacting with the mutation. 31 Bioinformatics tools including structure-prediction based molecular docking analysis were 32 applied. We found kinases such as EGFR might potentially act as new acceptors involving 33 the N501Y mutation binding through possible phosphorylation at Y501 and enhanced 34 affinity in certain variants. To our surprise, the Omicron receptor binding domain 35 harboring N501Y mutation did not enhance binding to EGFR which might be due to the LG-score indicates the reliability of the docking results and was calculated by ProQ program. Based on the LG-score, all the docked complexes were ranked in top hierarchy (LG-score > 5.0) (Larsson et al. 2009).

An aberrant 323 STAT pathway is central to COVID-19

Potential compound from 325 herbal food of Rhizoma Polygonati for treatment of COVID-19 analyzed by network 326 pharmacology: Viral and cancer signaling mechanisms

Rhizoma polygonati 330 from Mount Tai: nutritional value and usefulness as a traditional Chinese medicine, 331 source of herbzyme, and potential remediating agent for COVID-19 and chronic 332 and hidden hunger

OriginLab Corporation USA. 335 Accompanied by:1 user manual

The role of MET receptor tyrosine kinase in non-small 337 cell lung cancer and clinical development of targeted anti-MET agents

TCMSP: a database of systems pharmacology for drug discovery from 342 herbal medicines

Silico Investigation of the

New UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 Variants with a

Focus at the ACE2-Spike RBD Interface

GPS 5.0: an update on the prediction of kinase-specific 372 phosphorylation sites in proteins

Comparative Protein Structure Modeling Using Modeller

5.6.1-5.6.37, 2016. 375 29. WeiShengxin. 2013-. An online platform for data analysis and visualization