The emergence of a novel pathogenic human Coronavirus first reported in China, December 2019 has attracted global attention and poses a public health concern. Scientific studies and advancements since Severe Acute Respiratory Syndrome Coronavirus-1 (SARS-CoV-1) and Middle East Respiratory Syndrome (MERS) outbreaks have accelerated the understanding of the current Coronavirus disease-19 (Covid-19) pandemic especially in drug development. Here we explore the role of angiotensin converting enzyme-2 (ACE2); receptor for SARS-CoV-1 in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pathogenesis. ACE2 is found to be a functional receptor for SARS-CoV-2. The receptor binding domain structure of SARS-CoV-2 is similar to SARS-CoV-1 domain that interacts with ACE2. ACE2 is highly expressed in lung type II alveolar cells and infection with SARS-CoV-2 results in respiratory condition as reported in Covid-19 patients. It is highly expressed in other human organs including heart, kidneys, and the gastrointestinal tract, thereby posing high risk in Covid-19 infection and suggesting other alternative routes of transmission. The current study predicts that ACE2 allelic variants; rs73635825, rs1299103394, rs766996587, rs961360700, rs762890235, rs1396769231 have adverse impact on the encoded ACE2 possibly influencing resistance and susceptibility to Covid-19 infection, although no functional impact has been detected to date. Furthermore, use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers increases ACE2 expression levels with no associated risks in Covid-19 patients with comorbidities owing to the protective role of ACE2 in lung injury in animal disease models. The study results provide insight into the critical roles of ACE2 receptor and highlights potential targets for therapeutic interventions.

Covid-19, SARS-CoV-2, ACE2 receptors