Title:Exploring the SARS-Cov-2 Main Protease (Mpro) and RdRp Targets by
Updating Current Structure-based Drug Design Utilizing Co-crystals to
Combat COVID-19
Volume: 23
Issue: 8
Author(s): H. Tarannum, K.M. Rashmi and S. Nandi*
Affiliation:
- Global Institute of Pharmaceutical Education and Research, Kashipur-244713, India
Keywords:
COVID-19, SARS-CoV-2, Main protease, RNA dependent RNA polymerase (RdRp), co-crystallized ligand, mode of binding, structure-based crystallography.
Abstract: The unprecedented pandemic of COVID-19 caused by the novel strain of severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) engulfs millions of death worldwide. It has directly
hit the socio-economic status of the affected countries. There are more than 219 countries badly
affected by the COVID-19. There are no particular small molecule inhibitors to combat the dreadful
virus. Many antivirals, antimalarials, antiparasitic, antibacterials, immunosuppressive antiinflammatory,
and immune stimulatory agents have been repurposed for the treatment of COVID-19.
But the exact mechanism of action of these drugs towards COVID-19 targets has not been experimented
with yet. Under the effect of chemotherapeutics, the virus may change its genetic material and
produces various strains, which are the main reasons behind the dreadful attack of COVID-19. The
nuclear genetic components are composed of main protease and RNA-dependent RNA polymerase
(RdRp) which are responsible for producing nascent virion and viral replication in the host cells. To
explore the biochemical mechanisms of various small molecule inhibitors, structure-based drug design
can be attempted utilizing NMR crystallography. The process identifies and validates the target
protein involved in the disease pathogenesis by the binding of a chemical ligand at a well-defined
pocket on the protein surface. In this way, the mode of binding of the ligands inside the target cavity
can be predicted for the design of potent SARS-CoV-2 inhibitors.
