tetano
Editor, Senior Moderator
Curr Drug Targets
. 2021 Sep 6.
doi: 10.2174/1389450122666210906154849. Online ahead of print.
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
Heena Tarannum[SUP] 1 [/SUP], Rashmi Km[SUP] 2 [/SUP], Sisir Nandi[SUP] 2 [/SUP]
Affiliations
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 anti-inflammatory, and immune stimulatory agents have been repurposed for the treatment of COVID19. 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.
Keywords: COVID-19; Main protease; RNA dependent RNA polymerase (RdRp); SARS-CoV-2; co-crystallized ligand; mode of binding; structure-based crystallography.
. 2021 Sep 6.
doi: 10.2174/1389450122666210906154849. Online ahead of print.
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
Heena Tarannum[SUP] 1 [/SUP], Rashmi Km[SUP] 2 [/SUP], Sisir Nandi[SUP] 2 [/SUP]
Affiliations
- PMID: 34488580
- DOI: 10.2174/1389450122666210906154849
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 anti-inflammatory, and immune stimulatory agents have been repurposed for the treatment of COVID19. 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.
Keywords: COVID-19; Main protease; RNA dependent RNA polymerase (RdRp); SARS-CoV-2; co-crystallized ligand; mode of binding; structure-based crystallography.