The COVID-19 pandemic highlights the substantial public health, economic, and societal consequences of virus spillover from a wildlife reservoir. Widespread human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also presents a new set of challenges when considering viral spillover from people to naïve wildlife and other animal populations. Here, we used molecular dynamic (MD) simulations to understand the transmission of the SARS-CoV-2 virus from bats to humans and investigate the evolution of the various human variants. More specifically, we used MD simulations to understand the atomic fluctuation dampening at the receptor-binding domain (RBD)/ angiotensin-converting enzyme 2 (ACE2) interface when the RBD of the different SARS-CoV-2 variants is simulated with ACE2 of bat origin (bACE2) or human origin (hACE2). Towards that end, we found that the RaTG13 RBD is more stabilized with strong atomic fluctuation dampening when bound to bACE2 than hACE2. Interestingly, in terms of the variants being monitored (VBM - beta, kappa, and epsilon variants), we saw very similar binding dynamics and MD profiles between bACE2 and hACE2. Of note, when either bACE2 or hACE2 was simulated with variants of concern (VOC – alpha, delta, and omicron variants) RBD, we saw slightly stabilized atomic fluctuation dampening when the RBD was simulated with hACE2. Our results indicated that the RBD of the newer human SARS-CoV-2 variants does not differ significantly in the atomic fluctuation dampening when interacting with ACE2 of either bat or human origin. As a result, reverse zoonosis events that cause the virus to jump back to bats are highly possible, including the emergence of new and different variants. Therefore, in addition to the ongoing genomic surveillance, we also advise the inclusion of MD simulation surveillance that investigates the binding dynamics of the new variants with the receptors of the different host species.
Library of Congress Subject Headings
COVID-19 (Disease)--Transmission--Computer simulation; Molecular dynamics; Angiotensin converting enzyme; Zoonoses; Bats as carriers of disease; Carrier proteins
Department, Program, or Center
Thomas H. Gosnell School of Life Sciences (COS)
Rajendran, Madhusudan, "Functional evolutionary adaptation of binding dynamics in the SARS-CoV-2/ACE2 interface from bats to humans" (2022). Thesis. Rochester Institute of Technology. Accessed from
RIT – Main Campus