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bioRxiv · 10.1101/2020.12.27.424507

Losartan promotes cell survival following SARS-CoV-2 infection in vitro

Nejat, R.·Sadr, A. S.·Freitas, B. T.·Crabtree, J.·Pegan, S. D.·Tripp, R. A.·Najafi, D. J.
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Abstract

IntroductionCoronavirus disease 2019 (COVID-19) can be associated with mortality and high morbidity worldwide. There is an extensive effort to control infection and disease caused by SARS-CoV-2. This study addressed the hypothesis that angiotensin II type I receptor blocker, Losartan, may restrict pathogenesis caused by SARS-CoV-2 by decreasing viral-induced cytopathological changes by blocking angiotensin II type 1 receptor (AT1R), thus reducing the affinity of the virus for ACE2, and inhibiting papain-like protease of the virus. MethodLosartan inhibitory effect on deubiquitination and deISGylation properties of papain-like protease was investigated using a fluorescence method and gel shift analysis determining its inhibitory effects. The inhibitory effect of Losartan on SARS-CoV-2 cell replication was investigated both when losartan was added to the cell culture 1 hour before (pre-infection group) and 1 hour after (post-infection group) SARS-CoV-2 infection of Vero E6 cells. ResultsLosartan treatment of Vero E6 cells prior to and after SARS-CoV-2 infection reduced SARS-CoV-2 replication by 80% and 70% respectively. Losartan was not a strong deubiquitinase and deISGylase inhibitor of PLpro. ConclusionLosartan added pre- and post-infection to the Vero E6 cell culture significantly prevents cell destruction and replication by SARS-CoV2. Losartan has low side-effects, is readily available, and can be produced at high levels globally, all features of a promising drug in treatment of COVID-19 if validated by clinical trials.

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Nejat, R., Sadr, A. S., Freitas, B. T., Crabtree, J., Pegan, S. D., Tripp, R. A., Najafi, D. J.. 2020-12-28. Losartan promotes cell survival following SARS-CoV-2 infection in vitro. https://doi.org/10.1101/2020.12.27.424507

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