Abstract: Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Pharmacological Research 157 (2020) 104853 Contents lists available at ScienceDirect Pharmacological Research journal homepage: www.elsevier.com/locate/yphrs 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 Dear Editor, 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 [1]. 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 [2]. Extending the above-mentioned research to SARS-CoV-2, Matsuyama et al. [3] 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 [3]. 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 [4]. This is in addition to the demonstrated inhibitory role of cellular serine protease TMPRSS2 inhibitor in experimental SARS-CoV-2 entry [4]. 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 [5]. Activation of TMPRSS2 further plays a key role in other viral respiratory diseases https://doi.org/10.1016/j.phrs.2020.104853 Received 19 April 2020; Accepted 19 April 2020 Available online 30 April 2020 1043-6618/ © 2020 Elsevier Ltd. All rights reserved. T such as influenza A (as with MERS) and inhibition of viral activation by a serine protease inhibitor, the hepatocyte growth factor activator inhibitor..