In-silico investigation on the discovery of synthesized nucleoside-based antivirals against monkeypox and SARS-CoV-2 Virus

Abstract

Abstract The monkeypox virus and the SARS-CoV-2 virus serve as illustrative instances of agents that give rise to outbreaks. In the current study, we sought new broad-spectrum nucleoside-based antivirals that target viral particle attachment and target cell penetration. We used virtual molecular docking tools to assess the binding capability of the synthesized nucleoside-based medicines to the surface viral proteins and cell receptors. The results showed that the nucleoside-based antiviral drugs bounded well with the primary protease of SARS CoV-2 Mpro (PDB ID: 6LU7) and A42R Profilin-like protein of monkeypox virus (PDB ID: 4QWO). The interaction scores were observed to be of -7.82 kcal/mol by 8-amino G for 6LU7 and -7.95 kcal/mol by 8-Bromo A for 4QWO. The ligands tested were found to have high gastrointestinal absorption, with no blood-brain barrier permeability. The binding mode analysis revealed that most of the peptides that showed high interaction score were non-mutagenic but were found to be developmental toxicant. These compounds can be taken into consideration in the future for additional optimization and in-vitro experimental validation for the development of anti-susceptible drugs and vaccines.