Structural Dynamics and Molecular Evolution of the SARS-CoV-2 Spike Protein

mBio

Jeremy P. Kamil¹  Jason C. Kwan²  Kyle A. Wolf² 

[1] Department of Microbiology and Immunology, Louisiana State University Health Shreveport, Shreveport, Louisiana, USA;Department of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA;

关键词: SARS-CoV-2;    adaptive mutations;    coronavirus;    COVID-19;    evolution;    genomics;   

DOI  :  10.1128/mbio.02030-21

来源: DOAJ

【 摘 要 】

ABSTRACT The ongoing coronavirus disease 2019 (COVID-19) pandemic demonstrates the threat posed by novel coronaviruses to human health. Coronaviruses share a highly conserved cell entry mechanism mediated by the spike protein, the sole product of the S gene. The structural dynamics by which the spike protein orchestrates infection illuminate how antibodies neutralize virions and how S mutations contribute to viral fitness. Here, we review the process by which spike engages its proteinaceous receptor, angiotensin converting enzyme 2 (ACE2), and how host proteases prime and subsequently enable efficient membrane fusion between virions and target cells. We highlight mutations common among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern and discuss implications for cell entry. Ultimately, we provide a model by which sarbecoviruses are activated for fusion competency and offer a framework for understanding the interplay between humoral immunity and the molecular evolution of the SARS-CoV-2 Spike. In particular, we emphasize the relevance of the Canyon Hypothesis (M. G. Rossmann, J Biol Chem 264:14587–14590, 1989) for understanding evolutionary trajectories of viral entry proteins during sustained intraspecies transmission of a novel viral pathogen.

【 授权许可】

Unknown