tetano
Editor, Senior Moderator
J Phys Chem Lett
. 2020 May 28.
doi: 10.1021/acs.jpclett.0c01148. Online ahead of print.
Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity? Insights From All-Atoms Simulations
Angelo Spinello, Andrea Saltalamacchia, Alessandra Magistrato
Abstract
The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic is setting the global health crisis of our time, causing a devastating societal and economic burden. An idiosyncratic trait of coronaviruses is the presence of spike glycoproteins on the viral envelope, which mediate the virus binding to specific host receptor, enabling its entry into the human cells. In spite of the high sequence identity of SARS-CoV-2 with its closely related SARS-CoV emerged in 2002, the atomic-level determinants underlining the molecular recognition of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor and, thus, the rapid virus spread into human body, remain unresolved. Here, multi-?s-long molecular dynamics simulations enabled us to unprecedentedly dissect the key molecular traits liable of the higher affinity/specificity of SARS-CoV-2 towards ACE2, as compared to SARS-CoV, supplying a minute per-residue contact map underlining its stunningly high infectivity. Harnessing this knowledge is pivotal for urgently developing effective medical countermeasures to face the ongoing global health crisis.
. 2020 May 28.
doi: 10.1021/acs.jpclett.0c01148. Online ahead of print.
Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity? Insights From All-Atoms Simulations
Angelo Spinello, Andrea Saltalamacchia, Alessandra Magistrato
- PMID: 32463239
- DOI: 10.1021/acs.jpclett.0c01148
Abstract
The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic is setting the global health crisis of our time, causing a devastating societal and economic burden. An idiosyncratic trait of coronaviruses is the presence of spike glycoproteins on the viral envelope, which mediate the virus binding to specific host receptor, enabling its entry into the human cells. In spite of the high sequence identity of SARS-CoV-2 with its closely related SARS-CoV emerged in 2002, the atomic-level determinants underlining the molecular recognition of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor and, thus, the rapid virus spread into human body, remain unresolved. Here, multi-?s-long molecular dynamics simulations enabled us to unprecedentedly dissect the key molecular traits liable of the higher affinity/specificity of SARS-CoV-2 towards ACE2, as compared to SARS-CoV, supplying a minute per-residue contact map underlining its stunningly high infectivity. Harnessing this knowledge is pivotal for urgently developing effective medical countermeasures to face the ongoing global health crisis.