@article{Nejat_Sadr_Freitas_Crabttree_Pegan_Tripp_Najafi_2021, title={Losartan Inhibits SARS-CoV-2 Replication in Vitro: Losartan promotes cell survival following SARS-CoV-2 infection in vitro}, volume={24}, url={https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/31931}, DOI={10.18433/jpps31931}, abstractNote={<p><strong>Purpose: </strong>SARS-CoV-2 infection is associated with substantial mortality and high morbidity. This study tested the effect of angiotensin II type I receptor blocker, losartan, on SARS-CoV-2 replication and inhibition of the papain-like protease of the virus. <strong>Methods:</strong> The dose-dependent inhibitory effect of losartan, in concentrations from 1μM to 100μM as determined by quantitative cell analysis combining fluorescence microscopy, image processing, and cellular measurements (Cellomics analysis) on SARS-CoV-2 replication was investigated in Vero E6 cells. The impact of losartan on deubiquitination and deISGylation of SARS-CoV-2 papain-like protease (PLpro) were also evaluated.  <strong>Results:</strong> Losartan reduced PLpro cleavage of tetraUbiquitin to diUbiquitin.  It was less effective in inhibiting PLpro’s cleavage of ISG15-AMC than Ubiquitin-AMC.  To determine if losartan inhibited SARS-CoV-2 replication, losartan treatment of SARS-CoV-2 infected Vero E6 was examined. Losartan treatment one hour prior to SARS-CoV-2 infection reduced levels of SARS-CoV-2 nuclear protein, an indicator of virus replication, by 80% and treatment one-hour post-infection decreased viral replication by 70%. <strong>Conclusion:</strong> Losartan was not an effective inhibitor of deubiquitinase or deISGylase activity of the PLpro but affected the SARS-CoV-2 replication of Vero E6 cells <em>in vitro</em>.  As losartan has a favorable safety profile and is currently available it has features necessary for efficacious drug repurposing and treatment of COVID-19.</p>}, number={3}, journal={Journal of Pharmacy & Pharmaceutical Sciences}, author={Nejat, Reza and Sadr, Ahmad Shahir and Freitas, Branden and Crabttree, Jackelyn and Pegan, Scott D. and Tripp, Ralph A. and Najafi, David}, year={2021}, month={Jul.}, pages={390–399} }