Persistent cross-species SARS-CoV-2 variant infectivity predicted via comparative molecular dynamics simulation

Abstract

Widespread human transmission of SARS-CoV-2 highlights the substantial public health, economic and societal consequences of virus spillover from wildlife and also presents a repeated risk of reverse spillovers back to naive wildlife populations. We employ comparative statistical analyses of a large set of short-term molecular dynamic (MD) simulations to investigate the potential human-to-bat (genus Rhinolophus ) cross-species infectivity allowed by the binding of SARS-CoV-2 receptor-binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2) across the bat progenitor strain and emerging human strain variants of concern (VOC). We statistically compare the dampening of atom motion across protein sites upon the formation of the RBD/ACE2 binding interface using various bat versus human target receptors (i.e. bACE2 and hACE2). We report that while the bat progenitor viral strain RaTG13 shows some pre-adaption binding to hACE2, it also exhibits stronger affinity to bACE2. While early emergent human strains and later VOCs exhibit robust binding to both hACE2 and bACE2, the delta and omicron variants exhibit evolutionary adaption of binding to hACE2. However, we conclude there is a still significant risk of mammalian cross-species infectivity of human VOCs during upcoming waves of infection as COVID-19 transitions from a pandemic to endemic status.

ATOMDANCE: kernel-based denoising and allosteric resonance analysis for functional and evolutionary comparisons of protein dynamics

“…While the unfiltered divergence in viral-bound vs. unbound dynamics exhibits general dampening of ACE2 target protein’s motions (Figure 2C) the key functional sites of ACE2 that are recognized by the viral RBD are quite clearly and dramatically revealed by the MMD (Figure 3C). These include two sites on the N-terminal helices of ACE2 including two well documented additional sites identified at Q325 and K353 identified in previous studies of functional dynamics and evolution (Rajendran et al, 2022; Rajendran and Babbitt, 2022; Rynkiewicz et al, 2021).…”

Disentangling human nature: Anthropological reflections on evolution, zoonoses and ethnographic investigations

“…Consistent with this statement, zoonotic pathogens likely diffuse via human-induced alterations of ecosystems and climate change (Páez et al, 2018;Del Lesto et al, 2022). That said, like Yersinia pestis, which devastated Eurasian populations during the Neolithic (Andrades Valtueña et al, 2022), the new SARS-CoV-2 (Rajendran & Babbitt, 2022) reminds us that cross-species transmission depends significantly on the different modalities of human existence. Zoonoses, therefore, are the by-product of the entangled and intricate relationships among humans, different animal taxa, and their econiches (e.g., MacGregor & Waldman, 2017;Doron, 2021;Milstein et al, 2022;Shaffer et al, 2022;van Vliet et al, 2022;Arregui, 2023).…”

The Assessment of the Danger of Pathogens of Zoonotic Viral Infections as Potential Agents of Pandemics

“…Последствием передачи вируса от животных человеку стали пандемии СПИД [36], эпидемии MERS, SARS, свиного гриппа (H1N1) 2009 г. Последним примером такого рода стала пандемия новой коронавирусной болезни COVID-19 в 2019-2022 г., масштаб которой создал не только проблемы для экономики и здравоохранения, но и риски распространения вируса от человека в популяции диких животных, которые потенциально могут стать новыми резервуарами возбудителя в природе [37].…”