Losartan promotes cell survival following SARS-CoV-2 infection in vitro
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Introduction
Coronavirus 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.
Method
Losartan 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.
Results
Losartan 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.
Conclusion
Losartan 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.
Article activity feed
-
SciScore for 10.1101/2020.12.27.424507: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The virus was propagated for 72 hours before it was harvested and the titer determined by plaque assay on Vero E6 cells [78]. Vero E6suggested: RRID:CVCL_XD71)The Vero cells were plated at 5 × 105 cells/well in a 6-well plate and incubated overnight at 37°C. Verosuggested: NoneSoftware and Algorithms Sentences Resources These were all done in triplicate and the calculations were performed using Prism8 from GraphPad. GraphPadsuggested: …SciScore for 10.1101/2020.12.27.424507: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The virus was propagated for 72 hours before it was harvested and the titer determined by plaque assay on Vero E6 cells [78]. Vero E6suggested: RRID:CVCL_XD71)The Vero cells were plated at 5 × 105 cells/well in a 6-well plate and incubated overnight at 37°C. Verosuggested: NoneSoftware and Algorithms Sentences Resources These were all done in triplicate and the calculations were performed using Prism8 from GraphPad. GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
-
