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The biological mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus that causes coronavirus disease 2019 (COVID-19), enters human cells have been identified in detail.1 The key viral protein involved in cell entry is the spike (S) protein located on the surface of the virus particle. Two host-cell proteins, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine S2 (TMPRSS2), are also critical for cell entry. The viral S protein binds to ACE2, which serves as the cell membrane receptor for SARS-CoV-2, but only after the S protein has been “primed” by the action of the serine protease TMPRSS2. Thus, the host enzymes, ACE2 and TMPRSS2, act in concert to facilitate viral entry, setting the stage for the development of COVID-19.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Published Online: June 19, 2020. doi:10.1001/jama.2020.11401
Corresponding Author: Gregory Curfman, MD, JAMA, 330 N Wabash, Chicago, IL 60611 (firstname.lastname@example.org).
Conflict of Interest Disclosures: None reported.
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