jz0c01097_si_001.pdf (1.64 MB)
Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses
journal contribution
posted on 2020-07-02, 14:15 authored by Cécilia Hognon, Tom Miclot, Cristina Garcı́a-Iriepa, Antonio Francés-Monerris, Stephanie Grandemange, Alessio Terenzi, Marco Marazzi, Giampaolo Barone, Antonio MonariCoronaviruses
may produce severe acute respiratory syndrome (SARS).
As a matter of fact, a new SARS-type virus, SARS-CoV-2, is responsible
for the 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
the SARS viruses to bypass the host protective response. This work
also constitutes a first step in 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.