tetano
Editor, Senior Moderator
mBio
. 2022 Mar 8;e0203021.
doi: 10.1128/mbio.02030-21. Online ahead of print.
Structural Dynamics and Molecular Evolution of the SARS-CoV-2 Spike Protein
Kyle A Wolf[SUP] 1 2 [/SUP], Jason C Kwan[SUP] 1 [/SUP], Jeremy P Kamil[SUP] 3 4 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; adaptive mutations; coronavirus; evolution; genomics; glycoproteins; infectious disease; respiratory viruses; sarbecovirus; spike.
. 2022 Mar 8;e0203021.
doi: 10.1128/mbio.02030-21. Online ahead of print.
Structural Dynamics and Molecular Evolution of the SARS-CoV-2 Spike Protein
Kyle A Wolf[SUP] 1 2 [/SUP], Jason C Kwan[SUP] 1 [/SUP], Jeremy P Kamil[SUP] 3 4 [/SUP]
Affiliations
- PMID: 35258327
- DOI: 10.1128/mbio.02030-21
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.
Keywords: COVID-19; SARS-CoV-2; adaptive mutations; coronavirus; evolution; genomics; glycoproteins; infectious disease; respiratory viruses; sarbecovirus; spike.