Despite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges to researchers aiming to study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with its main host cell receptor, angiotensin-converting enzyme 2 (ACE2), has emerged as a critical focal point for the development of anti-viral therapeutics and vaccines. In this study, we selectively identify and characterize the impact of mutating certain amino acid residues in the RBD of SARS-CoV-2 and in ACE2, by utilizing our recently developed NanoBiT technology-based biosensor as well as pseudotyped-virus infectivity assays. Specifically, we examine the mutational effects on RBD-ACE2 binding ability, efficacy of competitive inhibitors, as well as neutralizing antibody activity. We also look at the implications the mutations may have on virus transmissibility, host susceptibility, and the virus transmission path to humans. These critical determinants of virus–host interactions may provide more effective targets for ongoing vaccines, drug development, and potentially pave the way for determining the genetic variation underlying disease severity.
【저자키워드】 SARS-CoV-2, Vaccine development, Drug development, angiotensin-converting enzyme 2, Spike protein, Receptor binding domain, NanoLuc Binary Technology, bioluminescence, 【초록키워드】 neutralizing antibody, Efficacy, ACE2, Mutation, Vaccines, Drug development, severity, virus transmission, underlying disease, SARS-CoV-1, angiotensin-converting enzyme 2, inhibitors, Anti-viral, Viral, RBD, humans, Genetic variation, target, pathogenicity, virulence, Critical, Angiotensin-converting enzyme, Amino acid, Interaction, angiotensin, host susceptibility, host cell, focal point, competitive inhibitors, determinant, sequence similarity, host cell receptor, researcher, binding ability, virus transmissibility, virus–host interactions, amino acid residue, Effect, widespread, implication, effective, RBD-ACE2, greater, identify, unique, demonstrated, the RBD, infectivity assays, virus–host interaction, 【제목키워드】 RBD, characterization, determinant,