6533b85ffe1ef96bd12c26ab
RESEARCH PRODUCT
Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity? Insights from All-Atom Simulations
Andrea SaltalamacchiaAngelo SpinelloAlessandra Magistratosubject
LettervirusesAmino Acid MotifsPneumonia ViralVirus Attachment02 engineering and technologyPlasma protein bindingBiologyPeptidyl-Dipeptidase AMolecular Dynamics SimulationVirus03 medical and health sciencesBetacoronavirusViral ProteinsProtein structureViral envelopeGlobal healthHumansGeneral Materials SciencePhysical and Theoretical ChemistryReceptorProtein Structure QuaternaryPandemics030304 developmental biologyGlycoproteinschemistry.chemical_classificationGeneticsInfectivity0303 health sciencesSARS-CoV-2virus diseasesCOVID-19Hydrogen Bonding021001 nanoscience & nanotechnologySARS VirusProtein Structure TertiarySevere acute respiratory syndrome-related coronaviruschemistrySettore CHIM/03 - Chimica Generale E InorganicaQuantum TheoryAngiotensin-Converting Enzyme 20210 nano-technologyGlycoproteinCoronavirus InfectionsProtein Bindingdescription
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-microsecond-long molecular dynamics simulations enabled us to unprecedentedly dissect the key molecular traits liable of the higher affinity/specificity of SARS-CoV-2 toward ACE2 as compared to SARS-CoV. This supplies 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-05-28 |