How virus size and attachment parameters affect the temperature sensitivity of virus binding to host cells: Predictions of a thermodynamic model for arboviruses and HIV

Abstract

Please cite this article as: Paul Gale , How virus size and attachment parameters affect the temperature sensitivity of virus binding to host cells: Predictions of a thermodynamic model for arboviruses and HIV, Microbial Risk Analysis (2020), doi: https://doi.

Thermodynamic equilibrium dose-response models for MERS-CoV infection reveal a potential protective role of human lung mucus but not for SARS-CoV-2

“…mucins and pathogen pattern recognition receptors to the lung epithelium. This is dependent on the fraction, F v , of the total virions (V mucus ) in the mucus which are not bound to mucin; Estimation of the probability, p pfu that a given virion (represented in the exposure as a viral RNA genomic copy) is fit and actually capable at the molecular level of binding to and initiating infection in a susceptible host cell such that it could be detected as a pfu; Calculation of C.V T as the fraction, F c , of viruses bound to cells based on the thermodynamics of virus/host cell binding and in particular the number and strength of the virus glycoprotein (GP)/cell receptor (Cr) interactions together with the parameter ΔS a_immob , which is the change in entropy on immobilization of whole virus on binding to the cell surface ( Gale 2019 ; Gale, 2020 ); and Estimation of the probability p cell which depends on the ability of the bound virus to enter the cell, replicate and bud releasing progeny virions (Gale, 2017).

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“…Calculation of C.V T as the fraction, F c , of viruses bound to cells based on the thermodynamics of virus/host cell binding and in particular the number and strength of the virus glycoprotein (GP)/cell receptor (Cr) interactions together with the parameter ΔS a_immob , which is the change in entropy on immobilization of whole virus on binding to the cell surface ( Gale 2019 ; Gale, 2020 ); and…”

“…Central to calculation of the number of lung epithelial cells with bound virus is the association constant, K a_virus_T which represents the strength of binding of whole virus to a lung cell at temperature T ( Gale 2019 , Gale, 2020 ). This is calculated as where K d_receptor_T is the dissociation constant for the CoV spike trimer protein from its proteinaceous cellular receptor, Cr, at temperature T, N v is the number of spike protein trimer/Cr interactions on virus/host cell binding and ΔS a_immob is the change in entropy on immobilization of whole virus on binding to the cell surface ( Gale 2019 , Gale, 2020 ).…”

“…Assuming half of this entropy is lost on cell binding and that the rotational entropy lost is similar ( Finkelstein and Janin 1989 ) then ΔS a_immob would approximate -350 J/mol/K although estimates based on Eq. 10 suggest values as low as -1,091 J/mol/K ( Gale 2020 ). This large negative entropy change may be offset to some degree by non-specific attachment of the virus to the cell surface through SA and heparan sulphate binding as proposed for HIV such that much of the entropy loss of ΔS a_immob on virus binding is taken prior to specific GP/Cr binding ( Gale 2020 ).…”

“…10 suggest values as low as -1,091 J/mol/K ( Gale 2020 ). This large negative entropy change may be offset to some degree by non-specific attachment of the virus to the cell surface through SA and heparan sulphate binding as proposed for HIV such that much of the entropy loss of ΔS a_immob on virus binding is taken prior to specific GP/Cr binding ( Gale 2020 ). For the purpose of the prototype model developed here a value of -350 J/mol/K is used for ΔS a_immob .…”