Role of SARS-CoV-2 and ACE2 variations in COVID-19

Abstract

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is one of the worst medical emergencies that has hit the world in almost a century. The virus has now spread to a large number of countries/territories and has caused over three million deaths. Evidently, the virus has been mutating and adapting during this period. Significant effort has been spent on identifying these variations and their impact on transmission, virulence and pathogenicity of SARS-CoV-2. Binding of the SARS-CoV-2 spike protein to the angiotensin converting enzyme 2 (ACE2) promotes cellular entry. Therefore, human ACE2 variations could also influence susceptibility or resistance to the virus. A deeper understanding of the evolution and genetic variations in SARS-CoV-2 as well as ACE2 could contribute to the development of effective treatment and preventive measures. Here, we review the literature on SARS-CoV-2 and ACE2 variations and their role in COVID-19.

Keywords: ACE2; COVID-19; SARS-CoV-2; Spike protein; Variations.

Fig. 1

Rendering of the SARS-CoV-2 spike glycoprotein trimer based on an X-ray crystal structure (Protein Data Bank ID: 6XLU) [83]. For clarity, only one subunit is shown in color while the other two are shown in translucent white cartoon representation. In the trimer, the S1 subunit is shown in orange and the RBD harbored within the S1 subunit is shown in pink. The S2 subunit is shown in yellow. Locations with mutations reported in the literature are shown in van der Waals representation. The image was rendered using Visual Molecular Dynamics 1.9.3 [84].