FIGURE 2.

SARS‐CoV‐2 structure, viral entry into host cells and the influence of testosterone. SARS‐CoV‐2 is made up of four structural proteins, including the spike (S), membrane, envelop and nucleocapsid proteins. The S protein has 2 functional domains known as S1 and S2. S1 is recognized and binds to angiotensin‐converting enzyme 2 (ACE2). Following ACE2 binding, cleavage of the viral spike protein (S) by proteases including transmembrane protease serine 2 (TMPRSS2) a crucial step to allow host cell membrane fusion and viral uptake. TMPRSS2 interacts with and primes ACE2 in this process and is considered crucial for host cell infection. TMPRSS2 transcription is exclusively regulated by the androgen receptor (AR) and ACE2 expression is increased in an androgen dependent manner (1). Mechanistically it is considered that androgen‐regulated TMPRSS2 promotes SARS‐CoV‐2 entry by two separate processes: ACE2 interaction/cleavage (2), which might promote viral uptake, and SARS‐2‐S cleavage, which enhances membrane fusion (3) via activation of the S protein. Created with BioRender.com