Angiotensin-converting enzyme 2 (ACE2) and Transmembrane protease serine 2 (TMPRSS2) (ACE2 and TMPRSS2)

Angiotensin-converting enzyme 2 (ACE2) and Transmembrane protease serine 2 (TMPRSS2) are two distinct host cell surface proteins that act cooperatively to facilitate the entry of coronaviruses, most notably SARS-CoV-2, into human cells [1, 4]. ACE2 is a zinc metalloprotease that primarily functions within the renin-angiotensin-aldosterone system (RAAS) to convert the vasoconstrictor angiotensin II into the vasodilator angiotensin (1-7), thereby providing cardioprotective and anti-inflammatory effects [6, 8, 10]. TMPRSS2 is a type II transmembrane serine protease that plays a critical role in viral infection by proteolytically cleaving or 'priming' the viral spike protein, a step essential for the fusion of the viral and host cell membranes [12, 14, 16]. In the context of COVID-19, ACE2 serves as the high-affinity binding receptor for the virus, while TMPRSS2 provides the necessary enzymatic activation for cell entry [1, 17]. Therapeutic strategies targeting this pathway include the use of soluble recombinant ACE2 as a decoy to trap the virus and serine protease inhibitors like camostat mesylate to block TMPRSS2 activity [4, 5, 20]. Additionally, because TMPRSS2 expression is regulated by androgens, antiandrogen therapies are being explored to reduce viral susceptibility [1, 3, 12].

Other names

ACEHAngiotensin-converting enzyme homologMetalloprotease M2EpitheliasinSerine protease 10PRSS10

Inhibition of viral entry via decoy receptor binding (ACE2) and blockade of proteolytic spike protein priming (TMPRSS2); transcriptional downregulation via androgen receptor antagonism [1, 4, 5, 12].