Post by Nadica (She/Her) on Sept 21, 2024 2:11:22 GMT
Host Manipulation Mechanisms of SARS-CoV-2 - Published Dec 13, 2021
Abstract
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.
Keywords: Host manipulation, SARS-CoV-2, Neuropilin, CendR motif, Mimicry, Polybasic cleavage site
Abstract
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.
Keywords: Host manipulation, SARS-CoV-2, Neuropilin, CendR motif, Mimicry, Polybasic cleavage site