Losartan Inhibits SARS-CoV-2 Replication in Vitro
PURPOSE: 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.
METHODS: 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. Results: 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%.
CONCLUSION: 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 in vitro. As losartan has a favorable safety profile and is currently available it has features necessary for efficacious drug repurposing and treatment of COVID-19.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
|---|---|
| Enthalten in: |
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques - 24(2021) vom: 31., Seite 390-399 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Nejat, Reza [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 06.08.2021 Date Revised 07.12.2022 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.18433/jpps31931 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM328645354 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM328645354 | ||
| 003 | DE-627 | ||
| 005 | 20231225203357.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.18433/jpps31931 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1095.xml |
| 035 | |a (DE-627)NLM328645354 | ||
| 035 | |a (NLM)34319871 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Nejat, Reza |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Losartan Inhibits SARS-CoV-2 Replication in Vitro |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.08.2021 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: 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 | ||
| 520 | |a METHODS: 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. Results: 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% | ||
| 520 | |a CONCLUSION: 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 in vitro. As losartan has a favorable safety profile and is currently available it has features necessary for efficacious drug repurposing and treatment of COVID-19 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Angiotensin II Type 1 Receptor Blockers |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Ubiquitin |2 NLM | |
| 650 | 7 | |a Deubiquitinating Enzymes |2 NLM | |
| 650 | 7 | |a EC 3.4.19.12 |2 NLM | |
| 650 | 7 | |a Coronavirus Papain-Like Proteases |2 NLM | |
| 650 | 7 | |a EC 3.4.22.2 |2 NLM | |
| 650 | 7 | |a papain-like protease, SARS-CoV-2 |2 NLM | |
| 650 | 7 | |a EC 3.4.22.2 |2 NLM | |
| 650 | 7 | |a Losartan |2 NLM | |
| 650 | 7 | |a JMS50MPO89 |2 NLM | |
| 700 | 1 | |a Sadr, Ahmad Shahir |e verfasserin |4 aut | |
| 700 | 1 | |a Freitas, Branden |e verfasserin |4 aut | |
| 700 | 1 | |a Crabttree, Jackelyn |e verfasserin |4 aut | |
| 700 | 1 | |a Pegan, Scott D |e verfasserin |4 aut | |
| 700 | 1 | |a Tripp, Ralph A |e verfasserin |4 aut | |
| 700 | 1 | |a Najafi, David |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques |d 1998 |g 24(2021) vom: 31., Seite 390-399 |w (DE-627)NLM097453277 |x 1482-1826 |7 nnns |
| 773 | 1 | 8 | |g volume:24 |g year:2021 |g day:31 |g pages:390-399 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.18433/jpps31931 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 24 |j 2021 |b 31 |h 390-399 | ||