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Systems analysis shows that thermodynamic physiological and pharmacological fundamentals drive COVID-19 and response to treatment

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dc.contributor.authorHead, R.J.
dc.contributor.authorLumbers, E.R.
dc.contributor.authorJarrott, B.
dc.contributor.authorTretter, F.
dc.contributor.authorSmith, G.
dc.contributor.authorPringle, K.G.
dc.contributor.authorIslam, S.
dc.contributor.authorMartin, J.H.
dc.date.issued2022
dc.description.abstractWhy a systems analysis view of this pandemic? The current pandemic has inflicted almost unimaginable grief, sorrow, loss, and terror at a global scale. One of the great ironies with the COVID-19 pandemic, particularly early on, is counter intuitive. The speed at which specialized basic and clinical sciences described the details of the damage to humans in COVID-19 disease has been impressive. Equally, the development of vaccines in an amazingly short time interval has been extraordinary. However, what has been less well understood has been the fundamental elements that underpin the progression of COVID-19 in an individual and in populations. We have used systems analysis approaches with human physiology and pharmacology to explore the fundamental underpinnings of COVID-19 disease. Pharmacology powerfully captures the thermodynamic characteristics of molecular binding with an exogenous entity such as a virus and its consequences on the living processes well described by human physiology. Thus, we have documented the passage of SARS-CoV-2 from infection of a single cell to species jump, to tropism, variant emergence and widespread population infection. During the course of this review, the recurrent observation was the efficiency and simplicity of one critical function of this virus. The lethality of SARS-CoV-2 is due primarily to its ability to possess and use a variable surface for binding to a specific human target with high affinity. This binding liberates Gibbs free energy (GFE) such that it satisfies the criteria for thermodynamic spontaneity. Its binding is the prelude to human host cellular entry and replication by the appropriation of host cell constituent molecules that have been produced with a prior energy investment by the host cell. It is also a binding that permits viral tropism to lead to high levels of distribution across populations with newly formed virions. This thermodynamic spontaneity is repeated endlessly as infection of a single host cell spreads to bystander cells, to tissues, to humans in close proximity and then to global populations. The principal antagonism of this process comes from SARS-CoV-2 itself, with its relentless changing of its viral surface configuration, associated with the inevitable emergence of variants better configured to resist immune sequestration and importantly with a greater affinity for the host target and higher infectivity. The great value of this physiological and pharmacological perspective is that it reveals the fundamental thermodynamic underpinnings of SARS-CoV-2 infection.
dc.identifier.citationPharmacology Research & Perspectives, 2022; 10(1, article no. e00922):1-22
dc.identifier.doi10.1002/prp2.922
dc.identifier.issn2052-1707
dc.identifier.issn2052-1707
dc.identifier.orcidHead, R.J. [0000-0002-1196-0926]
dc.identifier.urihttps://hdl.handle.net/11541.2/27398
dc.language.isoen
dc.publisherJohn Wiley & Sons
dc.rightsCopyright 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/)
dc.source.urihttps://doi.org/10.1002/prp2.922
dc.subjectACE2
dc.subjectaffinity
dc.subjectcomplex systems
dc.subjectCOVID-19
dc.subjectdissociation constant
dc.subjectGibbs free energy
dc.subjectinnate immunity
dc.subjectkinetics
dc.subjectlaw of mass action
dc.subjectMERS
dc.subjectpandemic
dc.subjectpharmacology
dc.subjectphysiology
dc.subjectrenin angiotensin system
dc.subjectSARS-CoV-1
dc.subjectSARS-CoV-2
dc.subjectthermodynamics
dc.subjecttropism
dc.subjectvariants
dc.subjectvirus
dc.subjectNasopharynx
dc.subjectAnimals
dc.subjectChiroptera
dc.subjectHumans
dc.subjectSystems Analysis
dc.subjectVirus Internalization
dc.subjectViral Tropism
dc.subjectInflammasomes
dc.titleSystems analysis shows that thermodynamic physiological and pharmacological fundamentals drive COVID-19 and response to treatment
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12240551400001831 13240551390001831 Pharmacology Res Perspec - 2022 - Head - Systems analysis shows that thermodynamic physiological and pharmacological
ror.mmsid9916609051201831

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