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Discovery of TMPRSS2 inhibitors from virtual screening.

ABSTRACT: The 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 MERS. Starting with comparative structural modeling and 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 (PP) entry assay. A number of novel inhibitors were identified, providing starting points for further development of drug candidates for the treatment of COVID-19.

SUBMITTER: Hu X

PROVIDER: S-EPMC7781311 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Discovery of TMPRSS2 inhibitors from virtual screening.

Hu Xin X Shrimp Jonathan H JH Guo Hui H Xu Miao M Chen Catherine Z CZ Zhu Wei W Zakharov Alexey A Jain Sankalp S Shinn Paul P Simeonov Anton A Hall Matthew D MD Shen Min M

bioRxiv : the preprint server for biology 20210317

The 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 MERS. Starting with comparative structural modeling and binding model ana ...[more]

PMID: 33398276

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