Structure and dynamics of RNA guanine quadruplexes in SARS-CoV-2 genome. Original strategies against emerging viruses

Abstract

Guanine quadruplexes (G4) structures in viral genome have a key role in modulating viruses' biological activity. While several DNA G4 structures have been experimentally resolved, RNA G4s are definitely less explored. We report the first calculated G4 structure of the RG-1 RNA sequence of SARS-CoV-2 genome, obtained by using a multiscale approach combining quantum and classical molecular modelling and corroborated by the excellent agreement between the corresponding calculated and experimental circular dichroism spectra. We prove the stability of RG-1 G4 arrangement as well as its interaction with G4 ligands potentially inhibiting viral protein translation.

Unlocking G‐Quadruplexes as Targets and Tools against COVID‐19

“…reported the first calculated RNA G4 structure of RG‐1 and proved the stability of the RG‐1 G4 arrangement as well as its interaction with G4 ligands, such as PDP and CX‐3543. [ 53 ] Berberine is a potential anti‐SARS‐CoV‐2 drug and Oliva et al . investigated the binding properties of RG‐1 to Berberine compared to telomeric G4, [ 54 ] contributing to the development of G4 ligands that can discriminate between binding to DNA and RNA G4s.…”

“…[ 27 ] However, due to the bioavailability issues, it was withdrawn from further trials. Recent research showed that CX‐3543 can potentially be seen as an effective compound to stabilize SARS‐CoV‐2 RG1, [ 53 ] indicating the potential of CX‐3543 for COVID‐19 therapy. Ribavirin is a well‐known antiviral drugs used for treating COVID‐19.…”