Publication: Anti-SARS-CoV-2 activity of extracellular vesicle inhibitors: Screening, validation, and combination with remdesivir
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Issued Date
2021-09-01
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22279059
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2-s2.0-85115237073
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Mahidol University
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SCOPUS
Bibliographic Citation
Biomedicines. Vol.9, No.9 (2021)
Suggested Citation
Supasek Kongsomros, Ampa Suksatu, Phongthon Kanjanasirirat, Suwimon Manopwisedjaroen, Somsak Prasongtanakij, Kedchin Jearawuttanakul, Suparerk Borwornpinyo, Suradej Hongeng, Arunee Thitithanyanont, Somchai Chutipongtanate Anti-SARS-CoV-2 activity of extracellular vesicle inhibitors: Screening, validation, and combination with remdesivir. Biomedicines. Vol.9, No.9 (2021). doi:10.3390/biomedicines9091230 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/76038
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Title
Anti-SARS-CoV-2 activity of extracellular vesicle inhibitors: Screening, validation, and combination with remdesivir
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Abstract
The coronavirus disease 2019 (COVID-19) pandemic severely impacts health, economy, and society worldwide. Antiviral drugs against SARS-CoV-2 are urgently needed to cope with this global crisis. It has been found that the biogenesis and release mechanisms of viruses share a common pathway with extracellular vesicles (EVs). We hypothesized that small molecule inhibitors of EV biogenesis/release could exert an anti-SARS-CoV-2 effect. Here, we screened 17 existing EV inhibitors and found that calpeptin, a cysteine proteinase inhibitor, exhibited the most potent anti-SARS-CoV-2 activity with no apparent cytotoxicity. Calpeptin demonstrated the dose-dependent inhibition against SARS-CoV-2 viral nucleoprotein expression in the infected cells with a half-maximal inhibitory concentration (IC50) of 1.44 µM in Vero-E6 and 26.92 µM in Calu-3 cells, respectively. Moreover, calpeptin inhibited the production of infectious virions with the lower IC50 of 0.6 µM in Vero E6 cells and 10.12 µM in Calu-3 cells. Interestingly, a combination of calpeptin and remdesivir, the FDA-approved antiviral drug against SARS-CoV-2 viral replication, significantly enhanced the anti-SARS-CoV-2 effects compared to monotherapy. This study discovered calpeptin as a promising candidate for anti-SARS-CoV-2 drug development. Further preclinical and clinical studies are warranted to elucidate the therapeutic efficacy of calpeptin and remdesivir combination in COVID-19.