ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
7 files
0/0

Homology Modeling of TMPRSS2 Yields Candidate Drugs That May Inhibit Entry of SARS-CoV-2 into Human Cells

preprint
submitted on 20.03.2020 and posted on 20.03.2020 by Stefano Rensi, Russ B Altman, Tianyun Liu, Yu-Chen Lo, Greg McInnes, Alex Derry, Allison Keys
The most rapid path to discovering treatment options for the novel coronavirus SARS-CoV-2 is to find existing medications that are active against the virus. We have focused on identifying repurposing candidates for the transmembrane serine protease family member II (TMPRSS2), which is critical for entry of coronaviruses into cells. Using known 3D structures of close homologs, we created seven homology models. We also identified a set of serine protease inhibitor drugs, generated several conformations of each, and docked them into our models. We used three known chemical (non-drug) inhibitors and one validated inhibitor of TMPRSS2 in MERS as benchmark compounds and found six compounds with predicted high binding affinity in the range of the known inhibitors. We also showed that a previously published weak inhibitor, Camostat, had a significantly lower binding score than our six compounds. All six compounds are anticoagulants with significant and potentially dangerous clinical effects and side effects. Nonetheless, if these compounds significantly inhibit SARS-CoV-2 infection, they could represent a potentially useful clinical tool.

Funding

NIH LM05652

NIH GM102365

NIH TR002515

NIH T32_LM 012409

NIH T15_LM 007033

NIH OT2 TR002515

History

Email Address of Submitting Author

srensi@stanford.edu

Institution

Stanford University

Country

USA

ORCID For Submitting Author

0000-0002-9309-4098

Declaration of Conflict of Interest

No conflict of interest

Exports

Logo branding

Exports