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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

Author(s):

Heena Tarannum, K.M. Rashmi and Sisir Nandi*   Pages 1 - 16 ( 16 )

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 di-rectly 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 anti-inflammatory, 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 experi-mented 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 de-sign 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.

Keywords:

COVID-19, SARS-CoV-2, Main protease, RNA dependent RNA polymerase (RdRp), co-crystallized ligand, mode of binding, structure-based crystallography.

Affiliation:

Six Sigma Institute of Technology and Science, Dineshpur, Rudrapur-263153, Global Institute of Pharmaceutical Education and Research, Kashipur-244713, Global Institute of Pharmaceutical Education and Research, Kashipur-244713



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