tetano
Editor, Senior Moderator
ACS Pharmacol Transl Sci
. 2021 Apr 2;4(3):1124-1135.
doi: 10.1021/acsptsci.0c00221. eCollection 2021 Jun 11.
Discovery of TMPRSS2 Inhibitors from Virtual Screening as a Potential Treatment of COVID-19
Xin Hu[SUP] 1 [/SUP], Jonathan H Shrimp[SUP] 1 [/SUP], Hui Guo[SUP] 1 [/SUP], Miao Xu[SUP] 1 [/SUP], Catherine Z Chen[SUP] 1 [/SUP], Wei Zhu[SUP] 1 [/SUP], Alexey V Zakharov[SUP] 1 [/SUP], Sankalp Jain[SUP] 1 [/SUP], Paul Shinn[SUP] 1 [/SUP], Anton Simeonov[SUP] 1 [/SUP], Matthew D Hall[SUP] 1 [/SUP], Min Shen[SUP] 1 [/SUP]
Affiliations
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted researchers to pivot their efforts to finding antiviral compounds and vaccines. In this study, we focused on the human host cell transmembrane protease serine 2 (TMPRSS2), which plays an important role in the viral life cycle by cleaving the spike protein to initiate membrane fusion. TMPRSS2 is an attractive target and has received attention for the development of drugs against SARS and Middle East respiratory syndrome. Starting with comparative structural modeling and a binding model analysis, we developed an efficient pharmacophore-based approach and applied a large-scale in silico database screening for small-molecule inhibitors against TMPRSS2. The hits were evaluated in the TMPRSS2 biochemical assay and the SARS-CoV-2 pseudotyped particle entry assay. A number of novel inhibitors were identified, providing starting points for the further development of drug candidates for the treatment of coronavirus disease 2019.
. 2021 Apr 2;4(3):1124-1135.
doi: 10.1021/acsptsci.0c00221. eCollection 2021 Jun 11.
Discovery of TMPRSS2 Inhibitors from Virtual Screening as a Potential Treatment of COVID-19
Xin Hu[SUP] 1 [/SUP], Jonathan H Shrimp[SUP] 1 [/SUP], Hui Guo[SUP] 1 [/SUP], Miao Xu[SUP] 1 [/SUP], Catherine Z Chen[SUP] 1 [/SUP], Wei Zhu[SUP] 1 [/SUP], Alexey V Zakharov[SUP] 1 [/SUP], Sankalp Jain[SUP] 1 [/SUP], Paul Shinn[SUP] 1 [/SUP], Anton Simeonov[SUP] 1 [/SUP], Matthew D Hall[SUP] 1 [/SUP], Min Shen[SUP] 1 [/SUP]
Affiliations
- PMID: 34136758
- PMCID: PMC8043206
- DOI: 10.1021/acsptsci.0c00221
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted researchers to pivot their efforts to finding antiviral compounds and vaccines. In this study, we focused on the human host cell transmembrane protease serine 2 (TMPRSS2), which plays an important role in the viral life cycle by cleaving the spike protein to initiate membrane fusion. TMPRSS2 is an attractive target and has received attention for the development of drugs against SARS and Middle East respiratory syndrome. Starting with comparative structural modeling and a binding model analysis, we developed an efficient pharmacophore-based approach and applied a large-scale in silico database screening for small-molecule inhibitors against TMPRSS2. The hits were evaluated in the TMPRSS2 biochemical assay and the SARS-CoV-2 pseudotyped particle entry assay. A number of novel inhibitors were identified, providing starting points for the further development of drug candidates for the treatment of coronavirus disease 2019.