In Vitro Inhibition of SARS-CoV-2 Infection by Bromhexine hydrochloride

Martins, R.; Ferreira, I.; Jorge, D. M.; Almeida, L.; Souza, J. d. P.; Pontelli, M. C.; Castro, I. A.; Melquiades, T.; Mendes Viana, R. M.; Zamboni, D. S.; Marcato, P.; Arruda, E.

doi:10.1101/2022.12.23.521817

bioRxiv · 10.1101/2022.12.23.521817

In Vitro Inhibition of SARS-CoV-2 Infection by Bromhexine hydrochloride

Martins, R.·Ferreira, I.·Jorge, D. M.·Almeida, L.·Souza, J. d. P.·Pontelli, M. C.·Castro, I. A.·Melquiades, T.·Mendes Viana, R. M.·Zamboni, D. S.·Marcato, P.·Arruda, E.

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Abstract

The world is enduring the SARS CoV-2 pandemic, and although extensive research has been conducted on the issue, only a few antivirals have been approved to treat patients with COVID-19. Bromhexine hydrochloride was previously identified as a potent inhibitor of TMPRSS2, an essential protease for ACE-2 virus receptor interactions. In the present study, we investigated whether bromhexine treatment could reduce SARS CoV-2 replication in vitro. To evaluate bromhexines effectiveness against SARS COV-2 infection, viral load was measured using Caco-2 cell lines expressing TMPRSS2. Our molecular docking results indicate that bromhexine displays an affinity with the active site of TMPRSS2. The drug significantly inhibited SARS CoV-2, both parental and P1 variant strains, infection in the Caco-2 cell line, reducing about 40% of SARS-CoV-2 entrance and about 90% of viral progeny in the supernatant 48h post-infection. Furthermore, bromhexine did not exhibit any direct virucidal activity on SARS CoV-2. In conclusion, bromhexine hydrochloride efficiently disrupts SARS CoV-2 infection in vitro and has the potential to become an effective antiviral agent in COVID-19 treatment.

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Martins, R., Ferreira, I., Jorge, D. M., Almeida, L., Souza, J. d. P., Pontelli, M. C., Castro, I. A., Melquiades, T., Mendes Viana, R. M., Zamboni, D. S., Marcato, P., Arruda, E.. 2022-12-26. In Vitro Inhibition of SARS-CoV-2 Infection by Bromhexine hydrochloride. https://doi.org/10.1101/2022.12.23.521817

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