The Genomic Physics of COVID-19 Pathogenesis and Spread

Abstract

Coronavirus disease (COVID-19) spreads mainly through close contact of infected persons, but the molecular mechanisms underlying its pathogenesis and transmission remain unknown. Here, we propose a statistical physics model to coalesce all molecular entities into a cohesive network in which the roadmap of how each entity mediates the disease can be characterized. We argue that the process of how a transmitter transforms the virus into a recipient constitutes a triad unit that propagates COVID-19 along reticulate paths. Intrinsically, person-to-person transmissibility may be mediated by how genes interact transversely across transmitter, recipient, and viral genomes. We integrate quantitative genetic theory into hypergraph theory to code the main effects of the three genomes as nodes, pairwise cross-genome epistasis as edges, and high-order cross-genome epistasis as hyperedges in a series of mobile hypergraphs. Charting a genome-wide atlas of horizontally epistatic hypergraphs can facilitate the systematic characterization of the community genetic mechanisms underlying COVID-19 spread. This atlas can typically help design effective containment and mitigation strategies and screen and triage those more susceptible persons and those asymptomatic carriers who are incubation virus transmitters.

Some mechanistic underpinnings of molecular adaptations of SARS-COV-2 spike protein by integrating candidate adaptive polymorphisms with protein dynamics

“…Long-ranged interactions between different sites within a given protein is critically important for protein function (Peters and Lively 1999 ;Bershtein et al 2006 ;Collins et al 2006 ;Ekeberg et al 2013 ;Levy et al 2017 ;Harrigan et al 2018 ;Otten et al 2018 ;Rojas Echenique et al 2019 ;Shimagaki and Weigt 2019 ;de la Paz et al 2020 ;Rizzato et al 2020 ;Yang et al 2020 ;Bisardi et al 2022 ) and for the CoV-2 S protein in particular (Zeng et al 2020 ;Castiglione et al 2021 ;Dong et al 2021 ;Garvin et al 2021 ;Nielsen et al 2022 ;Ramarao-Milne et al 2022 ;Rochman et al 2022 ;Rodriguez-Rivas et al 2022 ). By showing dynamic differences between the interactions of CAPs, which have likely played a major role in allowing the virus to infect human hosts, the binding site, and the characteristic mutations of dominant Delta and Omicron strains, we see a "fine-tuning" of protein behavior.…”

Some mechanistic underpinnings of molecular adaptations of SARS-COV-2 spike protein by integrating candidate adaptive polymorphisms with protein dynamics

“…Long-ranged interactions between different sites within a given protein are critically important for protein function ( Peters and Lively, 1999 ; Bershtein et al, 2006 ; Collins et al, 2006 ; Ekeberg et al, 2013 ; Levy et al, 2017 ; Harrigan et al, 2018 ; Otten et al, 2018 ; Rojas Echenique et al, 2019 ; Shimagaki and Weigt, 2019 ; de la Paz et al, 2020 ; Rizzato et al, 2020 ; Yang et al, 2020 ; Bisardi et al, 2022 ) and for the CoV-2 S protein in particular ( Zeng et al, 2020 ; Castiglione et al, 2021 ; Dong et al, 2021 ; Garvin et al, 2021 ; Nielsen et al, 2022 ; Ramarao-Milne et al, 2022 ; Rochman et al, 2022 ; Rodriguez-Rivas et al, 2022 ). By showing dynamic differences between the interactions of CAPs, which have likely played a major role in allowing the virus to infect human hosts, the binding site, and the characteristic mutations of dominant Delta and Omicron strains, we see a ‘fine-tuning’ of protein behavior.…”

Some mechanistic underpinnings of molecular adaptations of SARS-COV-2 spike protein by integrating candidate adaptive polymorphisms with protein dynamics

“…Long-ranged interactions between different sites within a given protein is critically important for protein function (Peters and Lively 1999; Bershtein et al 2006; Collins et al 2006; Ekeberg et al 2013; Levy et al 2017; Harrigan et al 2018; Otten et al 2018; Rojas Echenique et al 2019; Shimagaki and Weigt 2019; de la Paz et al 2020; Rizzato et al 2020; Yang et al 2020; Bisardi et al 2022) and for the CoV-2 S protein in particular (Zeng et al 2020; Castiglione et al 2021; Dong et al 2021; Garvin et al 2021; Nielsen et al 2022; Ramarao-Milne et al 2022; Rochman et al 2022; Rodriguez-Rivas et al 2022). By showing dynamic differences between the interactions of CAPs, which have likely played a major role in allowing the virus to infect human hosts, the binding site, and the characteristic mutations of dominant Delta and Omicron strains, we see a “fine-tuning” of protein behavior.…”