tetano
Editor, Senior Moderator
Bioorg Chem
. 2020 Sep 8;104:104269.
doi: 10.1016/j.bioorg.2020.104269. Online ahead of print.
Druggable targets of SARS-CoV-2 and treatment opportunities for COVID-19
Faheem[SUP] 1 [/SUP], Banoth Karan Kumar[SUP] 1 [/SUP], Kondapalli Venkata Gowri Chandra Sekhar[SUP] 2 [/SUP], Selvaraj Kunjiappan[SUP] 3 [/SUP], Joazaizulfazli Jamalis[SUP] 4 [/SUP], Rafael Bala?a-Fouce[SUP] 5 [/SUP], Babu L Tekwani[SUP] 6 [/SUP], Murugesan Sankaranarayanan[SUP] 7 [/SUP]
Affiliations
Abstract
COVID-19 caused by the novel SARS-CoV-2 has been declared a pandemic by the WHO is causing havoc across the entire world. As of May end, about 6 million people have been affected, and 367 166 have died from COVID-19. Recent studies suggest that the SARS-CoV-2 genome shares about 80% similarity with the SARS-CoV-1 while their protein RNA dependent RNA polymerase (RdRp) shares 96% sequence similarity. Remdesivir, an RdRp inhibitor, exhibited potent activity against SARS-CoV-2 in vitro. 3-Chymotrypsin like protease (also known as M[SUP]pro[/SUP]) and papain-like protease, have emerged as the potential therapeutic targets for drug discovery against coronaviruses owing to their crucial role in viral entry and host-cell invasion. Crystal structures of therapeutically important SARS-CoV-2 target proteins, namely, RdRp, M[SUP]pro[/SUP], endoribonuclease Nsp15/NendoU and receptor binding domain of CoV-2 spike protein has been resolved, which have facilitated the structure-based design and discovery of new inhibitors. Furthermore, studies have indicated that the spike proteins of SARS-CoV-2 use the Angiotensin Converting Enzyme-2 (ACE-2) receptor for its attachment similar to SARS-CoV-1, which is followed by priming of spike protein by Transmembrane protease serine 2 (TMPRSS2) which can be targeted by a proven inhibitor of TMPRSS2, camostat. The current treatment strategy includes repurposing of existing drugs that were found to be effective against other RNA viruses like SARS, MERS, and Ebola. This review presents a critical analysis of druggable targets of SARS CoV-2, new drug discovery, development, and treatment opportunities for COVID-19.
Keywords: Coronavirus; RNA virus; Respiratory disease; SARS-CoV-2; SARS-CoV-2 inhibitors.
. 2020 Sep 8;104:104269.
doi: 10.1016/j.bioorg.2020.104269. Online ahead of print.
Druggable targets of SARS-CoV-2 and treatment opportunities for COVID-19
Faheem[SUP] 1 [/SUP], Banoth Karan Kumar[SUP] 1 [/SUP], Kondapalli Venkata Gowri Chandra Sekhar[SUP] 2 [/SUP], Selvaraj Kunjiappan[SUP] 3 [/SUP], Joazaizulfazli Jamalis[SUP] 4 [/SUP], Rafael Bala?a-Fouce[SUP] 5 [/SUP], Babu L Tekwani[SUP] 6 [/SUP], Murugesan Sankaranarayanan[SUP] 7 [/SUP]
Affiliations
- PMID: 32947136
- DOI: 10.1016/j.bioorg.2020.104269
Abstract
COVID-19 caused by the novel SARS-CoV-2 has been declared a pandemic by the WHO is causing havoc across the entire world. As of May end, about 6 million people have been affected, and 367 166 have died from COVID-19. Recent studies suggest that the SARS-CoV-2 genome shares about 80% similarity with the SARS-CoV-1 while their protein RNA dependent RNA polymerase (RdRp) shares 96% sequence similarity. Remdesivir, an RdRp inhibitor, exhibited potent activity against SARS-CoV-2 in vitro. 3-Chymotrypsin like protease (also known as M[SUP]pro[/SUP]) and papain-like protease, have emerged as the potential therapeutic targets for drug discovery against coronaviruses owing to their crucial role in viral entry and host-cell invasion. Crystal structures of therapeutically important SARS-CoV-2 target proteins, namely, RdRp, M[SUP]pro[/SUP], endoribonuclease Nsp15/NendoU and receptor binding domain of CoV-2 spike protein has been resolved, which have facilitated the structure-based design and discovery of new inhibitors. Furthermore, studies have indicated that the spike proteins of SARS-CoV-2 use the Angiotensin Converting Enzyme-2 (ACE-2) receptor for its attachment similar to SARS-CoV-1, which is followed by priming of spike protein by Transmembrane protease serine 2 (TMPRSS2) which can be targeted by a proven inhibitor of TMPRSS2, camostat. The current treatment strategy includes repurposing of existing drugs that were found to be effective against other RNA viruses like SARS, MERS, and Ebola. This review presents a critical analysis of druggable targets of SARS CoV-2, new drug discovery, development, and treatment opportunities for COVID-19.
Keywords: Coronavirus; RNA virus; Respiratory disease; SARS-CoV-2; SARS-CoV-2 inhibitors.