SARS-CoV-2 is an endemic positive-sense RNA virus naturally transmissible between numerous species with notable infectivity and associated mortality. It is characterized by a poly-adenylated structure capping the genomic terminus. This poly(A) tail is crucial to a cascade of viral replicative activity occurring both extra- and intra-cellular during infection. As a route to proposing potential chemotherapy, this study suggests simple biplanar adenine quadruplexes (A4s) which may fold in specific sequences of the viral genome. To the best of our knowledge, uniquely biplanar A4s have not been previously described in any context. Using molecular modeling techniques and molecular dynamics simulations, some of these non-canonical structures show reasonable stability in a biological context. Notably, mRNA configured as a biplanar A4, shows less dynamic activity than DNA equivalents. This observation may be especially relevant in a physiological context. Furthermore, in contrast to well-characterized guanine quadruplexes, co-ordination with cations appears not to impact on stability. Our molecular dynamics simulations and analyses demonstrate that some A4s are stable in biologically relevant terms. These conclusions may apply to SARS-CoV-2, its variants and other pathogenic RNA viruses.
The Integrin Receptor in Biologically Relevant Bilayers: Insights from Molecular Dynamics Simulations
