Effect of Conformational Variability on Seasonable Thermal Stability and Cell Entry of Omicron Variants

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Feb 27

PMID 36844510

Authors

Hiroshi Izumi

Hiroshi Aoki

Laurence A Nafie

Rina K Dukor

Affiliations

Soon will be listed here.

Abstract

The Omicron BA.1 variant of SARS-CoV-2 preferentially infects through the cathepsin-mediated endocytic pathway, but the mechanism of cell entry has not been solved yet because BA.4/5 is more fusogenic and more efficiently spread in human lung cells than BA.2. It has been unclear why the Omicron spike is inefficiently cleaved in virions compared with Delta, and how the relatively effective reproduction proceeds without the cell entry through plasma membrane fusion. Conformational variability from deep neural network-based prediction correlates well with the thermodynamic stability of variants. The difference of seasonable pandemic variants in summer and those in winter is distinguishable by this conformational stability, and the geographical optimization of variants is also traceable. Further, the predicted conformational variability maps rationalize the less efficient S1/S2 cleavage of Omicron variants and provide a valuable insight into the cell entry through the endocytic pathway. It is concluded that conformational variability prediction is able to complement transformation information on motifs in protein structures for drug discovery.

Citing Articles

Supersecondary Structure Code for RNA: Trace of Conformational Change on the Ribosome and the R-Loop Formation of Cas9.

Izumi H, Nafie L, Dukor R ACS Omega. 2025; 10(5):4998-5005.

PMID: 39959072 PMC: 11822710. DOI: 10.1021/acsomega.4c10681.

Effect of Conformational Variability on the Drug Resistance of ERG11p and FKS1.

Izumi H, Nafie L, Dukor R ACS Omega. 2024; 9(18):19816-19823.

PMID: 38737078 PMC: 11080008. DOI: 10.1021/acsomega.3c08134.

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