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

Abstract

The world enduring the SARS CoV-2 pandemic, and although extensive research has been conducted on the issue, only a few antivirals have been approved up to date 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 evaluates the effectiveness of bromhexine against SARS COV-2 infection, viral load was measured using Caco-2 cell lines that express TMPRSS2. Our molecular docking results indicate that bromhexine displays an affinity with the active site of TMPRSS2. The drug was able to significantly inhibit 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.

Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial

“… 19 Fluvoxamine may also have antiviral effects through interaction with viral proteins and inhibition of acid sphingomyelinase. 12 , 20 , 21 , 22 Other commonly available drugs have immune-modulating and antiviral properties and have shown some evidence of effectiveness against SARS-CoV-2: Bromhexine hydrochloride acts as a mucolytic and immune modulator to help clear chest congestion, and as a TMPRSS2 protease blocker may be an effective antiviral against SARS-CoV-2 23 , 24 Cyproheptadine acts as an antagonist of 5-hydroxytryptamine (5HT/serotonin) receptor subtype two. It is an immune modulator to prevent potent effects of serotonin on lung vascular tone, respiratory rate, and systemic vascular beds, which may potentially affect COVID-19 clinical outcomes.…”