Thais Arns1, Aymeric Fouquier d’Hérouël1, Patrick May1, Alexandre Tkatchenko2 and Alexander Skupin1,2,3*
1 Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg
2 Department of Physics and Material Science, University of Luxembourg, Limpertsberg, Luxembourg
3 Department of Neuroscience, University of California San Diego, La Jolla, USA
alexander.skupin [at] uni.lu
Abstract
The COVID-19 pandemics has demonstrated the vulnerability of our societies to viral infectious disease. The mitigation of COVID-19 was complicated by the emergence of Variants of Concern (VOCs) with varying properties including increased transmissibility and immune evasion. Traditional population sequencing proved to be slow and not conducive for timely action. To tackle this challenge, we introduce the Persistence Score (PS) that assesses the pandemic potential of VOCs based on molecular dynamics of the interactions between the SARS-CoV-2 Receptor Binding Domain (RBD) and the ACE2 residues. Our mechanism-based classification approach successfully grouped VOCs into clinically relevant subgroups with higher sensitivity than classical affinity estimations and allows for risk assessment of hypothetical new VOCs. Interestingly, the PS-based interaction analysis across VOCs resembled the phylogenetic tree of SARS-CoV-2 with high accuracy and reveals for the first time a clear link between sequence determined structures and resulting molecular dynamics further demonstrating the predictive relevance for pandemic preparedness of our approach. Thus, PS allows for early detection of a variant’s pandemic potential, and an early risk evaluation for data-driven policymaking.
Keywords: molecular dynamics simulations, SARS-CoV-2 variants, phylogenetic tree, classification (up to 5)
Acknowledgement: This work was supported by the Luxembourg National Research Fund (FNR) COVID-19/21/16874499 – ERCSaCoV