The recent emergence of the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent for the coronavirus disease 2019 (COVID-19), is causing a global pandemic that poses enormous challenges to global public health and economies. SARS-CoV-2 host cell entry is mediated by the interaction of the viral transmembrane spike glycoprotein (S-protein) with the angiotensin-converting enzyme 2 gene (ACE2), an essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis. Accordingly, this work reports an atomistic-based, reliable in silico structural and energetic framework of the interactions between the receptor-binding domain of the SARS-CoV-2 S-protein and its host cellular receptor ACE2 that provides qualitative and quantitative insights into the main molecular determinants in virus/receptor recognition. In particular, residues D38, K31, E37, K353, and Y41 on ACE2 and Q498, T500, and R403 on the SARS-CoV-2 S-protein receptor-binding domain are determined as true hot spots, contributing to shaping and determining the stability of the relevant protein–protein interface. Overall, these results could be used to estimate the binding affinity of the viral protein to different allelic variants of ACE2 receptors discovered in COVID-19 patients and for the effective structure-based design and development of neutralizing antibodies, vaccines, and protein/protein inhibitors against this terrible new coronavirus.
【저자키워드】 ACE2, molecular dynamics, Receptor-binding domain, SARS-CoV-2 spike protein, computational alanine-scanning mutagenesis, molecular mechanics/Poisson−Boltzmann surface area, free energy of binding, 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, coronavirus, Vaccines, Neutralizing antibodies, ACE2 receptor, in silico, angiotensin-converting enzyme 2, global pandemic, stability, pathogen, glycoprotein, structure-based design, molecular, inhibitor, Quantitative, Critical, homeostasis, Blood, New coronavirus, Interaction, S-protein, COVID-19 patient, determinant, Volume, acute respiratory syndrome, Viral protein, Vascular, global public health, residue, domain, etiological agent, T500, cellular receptor, Host, effective, R403, Q498, K353, provide, the receptor-binding domain, contributing to, the binding affinity, allelic variant, D38, K31, SARS-CoV-2 host cell, the SARS-CoV-2, transmembrane spike, 【제목키워드】 spike, scanning, the SARS-CoV-2,