In Silico Comparison of Human ACE2 Interactions with SARS-CoV-2 Variants of Concern

The coronavirus SARS-CoV-2, responsible for the ongoing COVID-19 pandemic, must enter human cells before being able to replicate. The spike protein on the surface of the virus binds to an Angiotensin Converting Enzyme 2 (ACE2) receptor to gain access to the cells. As SARS-CoV-2 spreads and forms different variants, the interactions between the spike protein and ACE2 receptor change. Understanding the differences among these variants is critical in creating more informed responses to this pandemic. This study analyzed the differences among the binding of spike proteins from the Alpha, Beta, Gamma, and wild-type variants of SARS-CoV-2 and the human ACE2 by modeling their initial binding interactions and comparing the binding affinities, dissociation constants, and the interactions that make up the interfaces. These variants of SARS-CoV-2 are classified by the World Health Organization as variants of concern, meaning they show a significant change in the virus’ epidemiology, show an increase in transmissibility or virulence, or pose a threat to current measures to protect public health. Modeling the initial binding interactions and comparing the binding affinities, dissociation constants, and interactions that make up the interface showed significant differences in these properties. Most notably in this study, it was found that the wild-type SARS-CoV-2, had the highest binding affinity at -15.5 kcal/mol at 25 ℃ compared to the other variants tested, whilst the Alpha variant had the lowest at -12.2 kcal/mol. After binding interactions were modeled for the Alpha, Beta, and Gamma spike proteins of SARS-CoV-2 with ACE2, the interactions that made up the interface were listed and compared to the interactions from the binding of ACE2 and the wild-type SARS-CoV-2 spike protein. After counting the similar and unique interfacial interactions for every variant, it was found that the Alpha variant had the greatest number of unique interfacial interactions when compared with wild-type SARS-CoV-2. In contrast, this study shows that the Beta variant had the most similar interfacial interactions, compared to wild-type, when bound to ACE2.

Read the full presentation here!

https://docs.google.com/document/d/1YI6Su1vWAl0eqvk6hRWfZa27wvtlzZ3btj_Ktr6w9Io/edit

Hello! I'm Sebastian.

I applied to the New Hampsire Academy of Science when a friend recommended it to me, though I never imagined that it I could be doing this sort of research. Protein modeling was interesting to me because of the current pandemic we are living in, and I wanted to learn more about how this virus works, how it is changing, and what that means for our response.

Again, I want to thank the New Hampshire Academy of Science and my mentors Dr. Alyson Michael and Dr. Peter Faletra for this amazing experience!