Understanding the Infection and Possible Mutations of COVID-19

The findings are consistent with the hypothesis that bats are the viral origin and reservoir species.

Investigators at Pennsylvania State University, using computational modeling, have assessed how the changes of the coronavirus disease 2019 (COVID-19) virus’s spike protein makeup impacts binding with the human cell surface protein ACE2. The binding of these two proteins is the first step towards an infection which may result in COVID-19.

The research is one of the first projects undertaken to investigate SARS-CoV-2’s tendency to bind with human ACE2 using a computational model.

"We were interested in answering two important questions," Veda Sheersh Boorla, co-author on the paper said. "We wanted to first discern key structural changes that give COVID-19 a higher affinity towards human ACE2 proteins when compared with SARS, and then assess its potential affinity to livestock or other animal ACE2 proteins."

The paper, published in the journal Computational and Structural Biotechnology, used the modeling system to view SARS-CoV-2’s spike protein attaching to ACE2. The ACE2 protein is located in the upper respiratory tract, serving as an entry point for the coronavirus. Using molecular modeling, they computed the strength of the binding, as well as the interactions of the viral protein’s attachment to ACE2.

The findings showed that the SARS-CoV-2 spike protein is highly optimized to attach to and bind with the human ACE2 cell surface protein. The team also modeled various simulations of the virus attaching to homologous ACE2 proteins in animals such as cattle, felines, chickens, horses, canines and bats. The virus showed that it had a higher tendency to bind with bat ACE2, along with humans.

The data uncovered in the study is paramount for understanding the binding behavior of SARS-CoV-2 spike protein with the ACE2 protein and will help to inform future research on vaccine durability.

"The computational workflow that we have established should be able to handle other receptor binding-mediated entry mechanisms for other viruses that may arise in the future," Ratul Chowdhury, a doctoral student who worked on the study said.