Host Manipulation Mechanisms of SARS-CoV-2

Viruses are the simplest of pathogens, but possess sophisticated molecular mechanisms to manipulate host behavior, frequently utilizing molecular mimicry. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to bind to the host receptor neuropilin-1 in order to gain entry into...

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Bibliographic Details
Published in:Acta biotheoretica 2022-03, Vol.70 (1), p.4-4, Article 4
Main Author: Massey, Steven E.
Format: Article
Language:English
Subjects:
ACE2
Analgesia
Angiotensin-converting enzyme 2
Animals
Coronaviruses
Cough
COVID-19
Education
Epitopes
Evolutionary Biology
Humans
Interferon
Mimicry
Molecular modelling
Neuropilin
Olfaction
Pain perception
Philosophy
Philosophy of Biology
Protein Binding
Regular
Regular Article
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Sickness behavior
Spike Glycoprotein, Coronavirus - metabolism
Spike protein
Virus Internalization
Viruses
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Summary:Viruses are the simplest of pathogens, but possess sophisticated molecular mechanisms to manipulate host behavior, frequently utilizing molecular mimicry. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to bind to the host receptor neuropilin-1 in order to gain entry into the cell. To do this, the virus utilizes its spike protein polybasic cleavage site (PCS), which mimics the CendR motif of neuropilin-1’s endogenous ligands. In addition to facilitating cell entry, binding to neuropilin-1 has analgesic effects. We discuss the potential impact of neuropilin-1 binding by SARS-CoV-2 in ameliorating sickness behavior of the host, and identify a convergent evolutionary strategy of PCS cleavage and subsequent neuropilin binding in other human viruses. In addition, we discuss the evolutionary leap of the ancestor of SARS-COV-2, which involved acquisition of the PCS thus faciliting binding to the neuropilin-1 receptor. Acquisition of the PCS by the ancestor of SARS-CoV-2 appears to have led to pleiotropic beneficial effects including enhancement of cell entry via binding to ACE2, facilitation of cell entry via binding to neuropilin-1, promotion of analgesia, and potentially the formation of decoy epitopes via enhanced shedding of the S1 subunit. Lastly, other potential neuromanipulation strategies employed by SARS-CoV-2 are discussed, including interferon suppression and the resulting reduction in sickness behavior, enhanced transmission through neurally mediated cough induction, and reduction in sense of smell.
ISSN:0001-5342
1572-8358
DOI:10.1007/s10441-021-09425-z