ABSTRACT
In the frames of a One Health strategy, i.e. a strategy should be able to predict susceptibility to infection in both humans and animals, developing a SARS-CoV-2 mutation tracking system is a goal. We observed that the phylogenetic proximity of vertebrate ACE2 receptors does not affect the binding energy for the viral spike protein. However, all viral variants seem to bind ACE2 better in many animals than in humans. Moreover, two observations highlight that the evolution of the virus started at the beginning of 2020 and culminated with the appearance of the variants. First, codon usage analysis shows that the B.1.1.7 (alpha), B.1.351 (beta) and B.1.617.2 (delta) variants, similar in the use of codons, are also similar to a virus sampled in January 2020. Second, the host-specific D614G mutation becomes prevalent starting from March 2020. Overall, we show that SARS-CoV-2 undergoes a process of molecular evolution that begins with the optimization of codons followed by the functional optimization of the spike protein.
ABSTRACT
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.