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

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.

7 pages, 4 figures

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