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RESEARCH PRODUCT
Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses
Cécilia HognonAntonio MonariAntonio Francés-monerrisAntonio Francés-monerrisGiampaolo BaroneTom MiclotTom MiclotAlessio TerenziStéphanie GrandemangeMarco MarazziCristina Garcia Iriepasubject
Models Molecular0301 basic medicineLetterSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)DimerPneumonia ViralCoronaviruProtein dimerMolecular Dynamics SimulationViral infection01 natural sciencesVirusBetacoronavirus03 medical and health scienceschemistry.chemical_compound0302 clinical medicine0103 physical sciencesG-QuadruplexeHumans[CHIM]Chemical SciencesGeneral Materials Science030212 general & internal medicinePhysical and Theoretical ChemistryPandemicsEconomic consequences030304 developmental biology0303 health sciences010304 chemical physicsBetacoronaviruSARS-CoV-2ChemistryCoronavirus InfectionRational designCOVID-19RNASpike Glycoprotein3. Good healthG-Quadruplexes030104 developmental biologySettore CHIM/03 - Chimica Generale E InorganicaSpike Glycoprotein CoronavirusBiophysicsRNA ViralCoronavirus InfectionsGuanine-QuadruplexesDimerizationProtein Bindingdescription
ABSTRACTCoronaviruses may produce severe acute respiratory syndrome (SARS). As a matter of fact, a new SARS-type virus, SARS-CoV-2, is responsible of a global pandemic in 2020 with unprecedented sanitary and economic consequences for most countries. In the present contribution we study, by all-atom equilibrium and enhanced sampling molecular dynamics simulations, the interaction between the SARS Unique Domain and RNA guanine quadruplexes, a process involved in eluding the defensive response of the host thus favoring viral infection of human cells. Our results evidence two stable binding modes involving an interaction site spanning either the protein dimer interface or only one monomer. The free energy profile unequivocally points to the dimer mode as the thermodynamically favored one. The effect of these binding modes in stabilizing the protein dimer was also assessed, being related to its biological role in assisting SARS viruses to bypass the host protective response. This work also constitutes a first step of the possible rational design of efficient therapeutic agents aiming at perturbing the interaction between SARS Unique Domain and guanine quadruplexes, hence enhancing the host defenses against the virus.TOC GRAPHICS
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-04-10 |