Targeting Tmprss2, S-protein:Ace2, and 3CLpro for Synergetic Inhibitory Engagement

07 July 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

We are presenting our on going studies with inhibitory research on Tmprss2, S-protein:Ace2, and 3CLpro using compound screening coupled with X-ray crystallography, molecular modeling, live virus screening using host human cells (BSL3 facility at UC Center for Infectious Disease and Vector Research, and organ-on-a-chip at Harvard Medical School for safety profiling before proceeding to animal models with InVivo BioSystems for ADMET.
We have derived a useful chemical toolkit of 350 compounds for the community to study with biochemical assays and other biophysical-chemical studies that will prove useful in searching for optimal inhibitors of these targets to find suitable pharmacophores for blocking each of these enzyme's activities -- that would be beneficial for human health. Our past successes with these methodologies have resulted in over 28 patents, 11 technologies and two startup companies.

Keywords

Structural Biology
Crystallography
3CLpro
Tmprss2
S-protein:Ace2
protein-protein inhibitors
druggability
inhibitors
Medicinal chemistry approaches

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