Abstract: Internal and Emergency Medicine (2020) 15:801–812 https://doi.org/10.1007/s11739-020-02383-3 IM - REVIEW Potential new treatment strategies for COVID‑19: is there a role for bromhexine as add‑on therapy? Markus Depfenhart1,2 · Danielle de Villiers3 · Gottfried Lemperle4 · Markus Meyer5 · Salvatore Di Somma6,7 Received: 19 April 2020 / Accepted: 18 May 2020 / Published online: 26 May 2020 © Società Italiana di Medicina Interna (SIMI) 2020 Abstract Of huge importance now is to provide a fast, cost-effective, safe, and immediately available pharmaceutical solution to curb the rapid global spread of SARS-CoV-2. Recent publications on SARS-CoV-2 have brought attention to the possible benefit of chloroquine in the treatment of patients infected by SARS-CoV-2. Whether chloroquine can treat SARS-CoV-2 alone and also work as a prophylactic is doubtful. An effective prophylactic medication to prevent viral entry has to contain, at least, either a protease inhibitor or a competitive virus ACE2-binding inhibitor. Using bromhexine at a dosage that selectively inhibits TMPRSS2 and, in so doing, inhibits TMPRSS2-specific viral entry is likely to be effective against SARS-CoV-2. We propose the use of bromhexine as a prophylactic and treatment. We encourage the scientific community to assess bromhexine clinically as a prophylactic and curative treatment. If proven to be effective, this would allow a rapid, accessible, and cost-effective application worldwide. Keywords SARS-CoV-2 · COVID-19 · Prophylactic · Treatment · Bromhexine · Protease inhibitor Background “Pandemic is not a word to use lightly or carelessly.” stated Dr Tedros Adhanom Ghebreyesus, World Health Organization (WHO) Director-General, at a media briefing in March 2020 [1]. According to the WHO, as of April 18, 2020, coronavirus (CoV) disease 2019 (COVID-19) has caused more than 2,000,000 confirmed cases globally, and close to 150,000 deaths [2]. As the world witnesses the alarming * Markus Depfenhart dr@drdepfenhart.de 1 Faculty of Medicine, Venlo University B.V, Venlo, Netherlands 2 Medical One Clinic Hamburg, Hamburg, Germany 3 Research and Development, Medika SA, Pretoria, South Africa 4 Division of Plastic Surgery, University of California, San Diego, USA 5 Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia 6 Department of Medical‑Surgery Sciences and Translational Medicine, University of Rome Sapienza, Rome, Italy 7 GREAT Network Italy, Rome, Italy levels of spread and severity of atypical pneumonia COVID19, strategies to combat this outbreak are in dire need. The ripple effect of the COVID-19 outbreak is already starting to come to fruition, having devastating effects on human lives, globally impacting health systems and economies. The flourishing COVID-19 outbreak is reminiscent of epidemics that have caused panic in recent memory. These include SARS, MERS, the Zika virus, swine flu, and Ebola. This is the third documented coronavirus (CoV) transmission from animals to humans (zoonosis) in 2 decades. Previous outbreaks were severe acute respiratory syndrome coronavirus (SARS-CoV) [3, 4] and Middle-East respiratory syndrome coronavirus (MERS-CoV) [5]. We are now dealing with the novel CoV causing severe acute respiratory syndrome (SARS), originally termed 2019-nCoV, and now designated SARS-CoV-2 [6, 7]. CoVs are spherical enveloped single-stranded positivesense RNA viruses, characterized by club-like spikes that project from their surface giving them..