Evolution and Pathogenicity of SARS-CoVs: A Microcanonical Analysis of Receptor-Binding Motifs

TL;DR

This study uses advanced simulation techniques to analyze how sequence variations in the receptor-binding motifs of SARS coronaviruses affect their stability, folding, and solubility, shedding light on their evolution and pathogenicity.

Contribution

It introduces a microcanonical analysis approach to study the thermodynamics and structural transitions of RBMs across different SARS-CoV strains and variants.

Findings

Sequence variations impact RBM stability and folding dynamics.

Structural phase transitions correlate with viral evolution.

Solubility differences influence viral infectivity.

Abstract

The rapid evolution and global impact of coronaviruses, notably SARS-CoV-1 and SARS-CoV-2, underscore the importance of understanding their molecular mechanisms in detail. This study focuses on the receptor-binding motif (RBM) within the Spike protein of these viruses, a critical element for viral entry through interaction with the ACE2 receptor. We investigate the sequence variations in the RBM across SARS-CoV-1, SARS-CoV-2 and its early variants of concern (VOCs). Utilizing multicanonical simulations and microcanonical analysis, we examine how these variations influence the folding dynamics, thermostability, and solubility of the RBMs. Our methodology includes calculating the density of states (DoS) to identify structural phase transitions and assess thermodynamic properties. Furthermore, we solve the Poisson-Boltzmann equation to model the solubility of the RBMs in aqueous environments. This methodology is expected to elucidate structural and functional differences in viral evolution and pathogenicity, likely improving targeted treatments and vaccines.