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Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses
- Source :
- Journal of Physical Chemistry Letters, Journal of Physical Chemistry Letters, American Chemical Society, 2020, 11 (14), pp.5661-5667. ⟨10.1021/acs.jpclett.0c01097⟩, The Journal of Physical Chemistry Letters
- Publication Year :
- 2020
- Publisher :
- Cold Spring Harbor Laboratory, 2020.
-
Abstract
- Coronaviruses 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
- Subjects :
- Models, Molecular
0301 basic medicine
Letter
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Dimer
Pneumonia, Viral
Coronaviru
Protein dimer
Molecular Dynamics Simulation
Viral infection
01 natural sciences
Virus
Betacoronavirus
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
0103 physical sciences
G-Quadruplexe
Humans
[CHIM]Chemical Sciences
General Materials Science
030212 general & internal medicine
Physical and Theoretical Chemistry
Pandemics
Economic consequences
030304 developmental biology
0303 health sciences
010304 chemical physics
Betacoronaviru
SARS-CoV-2
Chemistry
Coronavirus Infection
Rational design
COVID-19
RNA
Spike Glycoprotein
3. Good health
G-Quadruplexes
030104 developmental biology
Settore CHIM/03 - Chimica Generale E Inorganica
Spike Glycoprotein, Coronavirus
Biophysics
RNA, Viral
Coronavirus Infections
Guanine-Quadruplexes
Dimerization
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 19487185
- Database :
- OpenAIRE
- Journal :
- Journal of Physical Chemistry Letters, Journal of Physical Chemistry Letters, American Chemical Society, 2020, 11 (14), pp.5661-5667. ⟨10.1021/acs.jpclett.0c01097⟩, The Journal of Physical Chemistry Letters
- Accession number :
- edsair.doi.dedup.....b3d9c27314579c6a25b87d4a4dc908cf
- Full Text :
- https://doi.org/10.1101/2020.04.07.029447