Possible use of the mucolytic drug, bromhexine hydrochloride, as a prophylactic agent against SARS-CoV-2 infection based on its action on the Transmembrane Serine Protease 2
Habtemariam et al.
, Possible use of the mucolytic drug, bromhexine hydrochloride, as a prophylactic agent against SARS-CoV-2..
, Pharmacol. Res., doi:10.1016/j.phrs.2020.104853 (Theory)
Note on the potential use of bromhexine hydrochloride for prophylaxis of SARS-CoV-2, based on the role of TMPRSS2 in SARS-CoV-2 infection, and the TMPRSS2 inhibition of bromhexine hydrochloride.
Habtemariam et al., 30 Apr 2020, peer-reviewed, 6 authors.
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Pharmacological Research 157 (2020) 104853
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Letter to the Editor
Possible use of the mucolytic drug, bromhexine hydrochloride, as a prophylactic agent against
SARS-CoV-2 infection based on its action on the Transmembrane Serine Protease 2
As with all new virus diseases with no drug therapy, identifying key
pharmacological targets for SARS-coronavirus 2 (SARS-CoV-2 or 2019nCoV) based on our knowledge of the viral entry and replication mechanisms in host cells is critical. The present insight highlights the
possibility of targeting the Transmembrane Serine Protease 2
(TMPRSS2) to tackle COVID-19, based on similarities with other known
coronaviruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS).
The entry of coronavirus into host cells requires proteolytic activation by protease enzymes and several such potential targets have
already been identified. New evidence suggests that TMPRSS2 is involved in MERS and SARS-CoV S protein processing for infection in a
number of susceptible host cells in cell lines obtained from various
organs . In the murine models of infection by SARS-CoV and MERSCoV, for example, TMPRSS2-knockout mice exhibit lower level of viral
spread in the lungs coupled with reduced severity in immunopathology
Extending the above-mentioned research to SARS-CoV-2,
Matsuyama et al.  have shown that VeroE6 cells expressing
TMPRSS2 are highly susceptible to infection. By using TMPRSS2
overexpression as a tool, the isolation of SARS-CoV-2 is more readily
possible . While both ACE2 and TMPRSS2 have been shown to be
involved in the entry of SARS-CoV-2 via S protein activation, sera from
convalescent SARS patients have been shown to cross-neutralize SARSCoV2-S-mediated entry into a large number of sensitive cell lines .
This is in addition to the demonstrated inhibitory role of cellular serine
protease TMPRSS2 inhibitor in experimental SARS-CoV-2 entry . A
recent study on the expression level of TMPRSS2 showed that it is
widely expressed in lung tissues while ACE2 is predominantly expressed
in a transient secretory cell types or differentiating cells . Activation
of TMPRSS2 further plays a key role in other viral respiratory diseases
Received 19 April 2020; Accepted 19 April 2020
Available online 30 April 2020
1043-6618/ © 2020 Elsevier Ltd. All rights reserved.
such as influenza A (as with MERS) and inhibition of viral activation by
a serine protease inhibitor, the hepatocyte growth factor activator inhibitor..
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