tetano
Editor, Senior Moderator
Comput Biol Chem
. 2020 Jul 31;88:107351.
doi: 10.1016/j.compbiolchem.2020.107351. Online ahead of print.
Repurposing approved drugs as potential inhibitors of 3CL-protease of SARS-CoV-2: Virtual screening and structure based drug design
Franz-Josef Meyer-Almes[SUP] 1 [/SUP]
Affiliations
Abstract
3CL proteases (3CL[SUP]pro[/SUP]) are only found in RNA viruses and have a central role in polyprotein processing during replication. Therefore, 3CL[SUP]pro[/SUP] has emerged as promising drug target for therapeutic treatment of infections caused by Coronaviruses. In the light of the recent major outbreak of the SARS-CoV-2 virus and the continuously rising numbers of infections and casualties, there is an urgent need for quickly available drugs or vaccines to stop the current COVID-19 pandemic. Repurposing of approved drugs as 3CL[SUP]pro[/SUP] inhibitors could dramatically shorten the period up to approval as therapeutic against SARS-CoV-2, since pharmacokinetics and toxicity is already known. Several known drugs, e.g. oxytetracycline, doxorubicin, kanamycin, cefpiramide, teniposide, proanthocyanidin and salvianolic acid B, but also not-approved active compounds from the ZINC15 library were identified as new potential inhibitors of 3CL[SUP]pro[/SUP] by using different complementary virtual screening and docking approaches. These compounds have the potential to be further optimized using structure based drug design as demonstrated for oxytetracycline.
Keywords: Antiviral; C30 endopeptidase; COVID-19; Docking; Drug discovery; Pharmacophore; Therapeutic.
. 2020 Jul 31;88:107351.
doi: 10.1016/j.compbiolchem.2020.107351. Online ahead of print.
Repurposing approved drugs as potential inhibitors of 3CL-protease of SARS-CoV-2: Virtual screening and structure based drug design
Franz-Josef Meyer-Almes[SUP] 1 [/SUP]
Affiliations
- PMID: 32769050
- DOI: 10.1016/j.compbiolchem.2020.107351
Abstract
3CL proteases (3CL[SUP]pro[/SUP]) are only found in RNA viruses and have a central role in polyprotein processing during replication. Therefore, 3CL[SUP]pro[/SUP] has emerged as promising drug target for therapeutic treatment of infections caused by Coronaviruses. In the light of the recent major outbreak of the SARS-CoV-2 virus and the continuously rising numbers of infections and casualties, there is an urgent need for quickly available drugs or vaccines to stop the current COVID-19 pandemic. Repurposing of approved drugs as 3CL[SUP]pro[/SUP] inhibitors could dramatically shorten the period up to approval as therapeutic against SARS-CoV-2, since pharmacokinetics and toxicity is already known. Several known drugs, e.g. oxytetracycline, doxorubicin, kanamycin, cefpiramide, teniposide, proanthocyanidin and salvianolic acid B, but also not-approved active compounds from the ZINC15 library were identified as new potential inhibitors of 3CL[SUP]pro[/SUP] by using different complementary virtual screening and docking approaches. These compounds have the potential to be further optimized using structure based drug design as demonstrated for oxytetracycline.
Keywords: Antiviral; C30 endopeptidase; COVID-19; Docking; Drug discovery; Pharmacophore; Therapeutic.