Molecular docking simulation reveals ACE2 polymorphisms that may increase the affinity of ACE2 with the SARS-CoV-2 Spike protein

There is increasing evidence that ACE2 gene polymorphism can modulate the interaction between ACE2 and the SARS-CoV-2 spike protein affecting the viral entry into the host cell, and/or contribute to lung and systemic damage in COVID-19. Here we used in silico molecular docking to predict the effects of ACE2 missense variants on the interaction with the spike protein of SARS-CoV-2. HDOCK and FireDock simulations identified 6 ACE2 missense variants (I21T, A25T, K26R, E37K, T55A, E75G) with higher affinity for SARS-CoV-2 Spike protein receptor binding domain (RBD) with respect to wild type ACE2, and 11 variants (I21V, E23K, K26E, T27A, E35K, S43R, Y50F, N51D, N58H, K68E, M82I) with lower affinity. This result supports the hypothesis that ACE2 genetic background may represent the first genetic gateway during the disease progression. (C) 2020 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.

Automated summary

There is evidence that ACE2 gene polymorphisms can affect the interaction between ACE2 and the SARS-CoV-2 spike protein, potentially influencing viral entry into host cells. In silico molecular docking predicted that certain ACE2 missense variants have higher or lower affinity for the SARS-CoV-2 spike protein receptor binding domain, supporting the hypothesis that ACE2 genetic background may play a role in disease progression.