Viral genome targeting for anti-viral drug discovery and vaccine development against Monkeypox virus

Abstract

G-quadruplexes (GQs) are one of the most extensively researched non-canonical secondary structures of nucleic acids and are ubiquitously present in all species, from viruses to prokaryotes and eukaryotes. GQs are formed by staking of more than one G-tetrad, and each G-tetrad is made by non-canonical reciprocal interaction of Guanine residues arrayed in a plane. G quadruplexes are present in the regulatory regions, mostly in promoter, intron, and telomeres. Due to the presence of these motifs in regulatory regions, they assist in various biological processes, for example, replication, transcription, repair & recombination, and telomere maintenance. The development of novel therapeutics relies on identifying novel drug targets that are evolutionary conserved in monkeypox virus and their nucleic acid act as better receptors for developing novel anti-viral drugs. Multiple studies have been done on several viruses including Ebola, Zika, Human adenovirus, HIV, and HCV etc, showing the presence and regulatory role of GQ motifs in viral replication and amplification. Therefore, they are used as a potential anti viral therapeutic target. Similarly, we move forward with the monkeypox virus, In our initial studies we identified the highly conserved GQ motifs in the genome of monkeypox virus that might play a critical role in their growth and amplification. We further analyzed with G-quadruplex ligands like Braco-19 and analyze their interaction, binding, and stability in the presence of these drugs.