Functional Variants in Human ACE2 Can Decrease its Protein Stability and May Influence the Binding with SARS-CoV-2

Abstract

As for the transmission of human to human, the recent pandemic of COVID-19 is now spreading among the population, which has already led to 1.86 million deaths. As recently reported, it is the SARS-CoV-2 that causes COVID-19. Furthermore, human ACE2 is the receptor of the coronavirus. Nowadays, it has been reported that missense variants in ACE2 may affect the coronavirus susceptibility. In this work, we explored the functional impacts of missense variants in human ACE2. Briefly, we initially collected the variant in human ACE2, which have been labeled as important sites of ACE2 or the critical binding sites with the spike protein. Thereafter, applying the technology of protein structure homology modeling, we constructed the molecular spatial structure models of the variants. Next, variants molecular models of ACE2 were superimposed over the wild type of ACE2, to observe the structural changes. As experimental results demonstrated, the overall structures of ACE2 variants are similar. However, several variants (i.e., G173S, V184A, I233F, D355N, R357A, R357S, and G575V) in ACE2 are predicted to decrease the stability of human ACE2 protein and/or to be harmful to human health. Accordingly, the final findings could also provide a functional and structural basis for the potential pathogenicity of ACE2-driven viral infections.