Reckoning a fungal metabolite, Pyranonigrin A as a potential Main protease (M(pro)) inhibitor of novel SARS-CoV-2 virus identified using docking and molecular dynamics simulation

Rao, Priyashi; Shukla, Arpit; Parmar, Paritosh; Rawal, Rakesh M.; Patel, Baldev; Saraf, Meenu; Goswami, Dweipayan

The novel SARS-CoV-2 is the etiological agent causing the Coronavirus disease 2019 (COVID-19), which continues to become an inevitable pandemic outbreak. Over a short span of time, the structures of therapeutic target proteins for SARS-CoV-2 were identified based on the homology modelled structure of similar SARS-CoV transmission of 2003. Since the onset of the disease, the research community has been looking for a potential drug lead. Out of all the known resolved structures related to SARS-CoV, Main protease (M(pro)) is considered an attractive anti-viral drug target on the grounds of its role in viral replication and probable non-interactive competency to bind to any viral host protein. To the best of our knowledge, till date only one compound has been identified and tested in-vivo as a potent inhibitor of M(pro) protein, addressed as N3 (PubChem Compound CID: 6323191) and is known to bind irreversibly to M(pro) suppressing its activity. Using computational approach, we intend to identify a probable natural fungal metabolite to interact and inhibit M(pro). After screening various small molecules for molecular docking and dynamics simulation, we propose Pyranonigrin A, a secondary fungal metabolite to possess potent inhibitory potential against the Main protease (M(pro)) expressed in SARS-CoV-2 virus.