ACE2: The Only Thing That Matters?

In December 2019, cases of a respiratory disease were reported in Hubei Province, China, caused by a positive-sense RNA virus from the family Coronaviridae. Subsequently, the disease was called coronavirus disease (COVID-19) and the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outcome of infection with SARS-CoV-2 is highly variable; on one hand, the virus has been responsible for more than 360,000 deaths worldwide, and on the other hand, there is a diverse range of clinical outcomes in different people. For any virus, infection depends on the ability to 1) enter, 2) evade cellular defenses, 3) hijack host machineries to express viral genes, 4) replicate new genomes, 5) assemble viral particles, and 6) exit. For SARS-CoV-2 entry, the primary receptor is ACE2 (angiotensin I--converting enzyme 2), which serves as receptor for SARS-CoV and a human seasonal coronavirus, human coronavirus NL63 (HCoV-NL63). The physiological role of ACE2 is the regulation of the reninangiotensin hormone system, regulating blood volume, systemic vascular resistance, and cardiovascular homeostasis.