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

Martins et al., bioRxiv, doi:10.1101/2022.12.23.521817
Dec 2022  
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In Vitro study showing that bromhexine inhibits SARS-CoV-2 infection and replication in vitro by blocking the host cell protease TMPRSS2.
Bromhexine efficacy may vary depending on the degree of TMPRSS-dependent fusion for different variants Peacock, Willett.
4 preclinical studies support the efficacy of bromhexine for COVID-19:
Martins et al., 26 Dec 2022, preprint, 12 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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In Vitro Inhibition of SARS-CoV-2 Infection by Bromhexine hydrochloride
Ronaldo Martins, Iasmin Ferreira, Daniel M M Jorge, Leticia Almeida, Juliano P Souza, Marjorie Pontelli, Italo A Castro, Thais M Lima, Rosa M M Viana, Dario Zamboni, Priscyla D Marcato, Eurico Arruda
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 bromhexine's 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 postinfection. Furthermore, bromhexine did not exhibit any direct virucidal activity on .
Almeida, Juliano P. Souza, Marjorie Pontelli, Italo A. Castro, Thais M. Lima, and Rosa M. M. Viana designed and executed the experimental SARS-CoV-2 infection. All authors contributed to writting the manuscript. Eurico Arruda, Priscyla D. Marcato, and RBM wrote the final version of the manuscript. All authors have approved the final manuscript. Declaration of Competing Interests The authors declare no conflict of interest.
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