Several viruses, including SARS-CoV-2, use the protease activity of the TMPRSS2 protein in the process of entering cells.

The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage.

[13][14] Interestingly, SRCR may have a role in overall proteolytic activity of the protein, which could lead to implications on the overall virulence of SARS-CoV-2.

[15][12][16] TMPRSS2 protein's function in prostate carcinogenesis relies on overexpression of ETS transcription factors, such as ERG and ETV1, through gene fusion.

ERG overexpression contributes to development of androgen-independence in prostate cancer through disruption of androgen receptor signaling.

[22] The enzyme Adam17 has similar ACE2 cleavage activity as TMPRSS2, but by forming soluble ACE2, Adam17 may actually have the protective effect of blocking circulating SARS‑CoV‑2 virus particles.

[20][22] Another experimental candidate as a TMPRSS2 inhibitor for potential use against both influenza and coronavirus infections in general, including those prior to the advent of COVID-19, is the over-the-counter (in most countries) mucolytic cough medicine bromhexine,[24] which is also being investigated as a possible treatment for COVID-19 itself as well.