Paramyxoviruses: Parainfluenza Viruses

Englund, Janet A.; Moscona, Anne

doi:10.1007/978-1-4899-7448-8_25

Cited by 8 publications

(8 citation statements)

References 247 publications

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“…The HPIV species viruses are responsible for 30–40% of all acute respiratory tract infections in infants and children1. Nipah virus (NiV) is a zoonotic paramyxovirus of the henipavirus genus that represents a global health risk with broad, unpredictable pandemic potential.…”

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confidence: 99%

“…Human parainfluenza viruses (HPIVs) are paramyxoviruses belonging to the respirovirus (HPIV1 and 3) or rubulavirus (HPIV2 and 4) genera that cause human respiratory diseases including bronchitis, bronchiolitis, and pneumonia in infants, children, or immune-compromised individuals. The HPIV species viruses are responsible for 30–40% of all acute respiratory tract infections in infants and children 1 . Nipah virus (NiV) is a zoonotic paramyxovirus of the henipavirus genus that represents a global health risk with broad, unpredictable pandemic potential.…”

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confidence: 99%

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Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides

Mathieu

Augusto

Niewiesk

et al. 2017

Sci Rep

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Human paramyxoviruses include global causes of lower respiratory disease like the parainfluenza viruses, as well as agents of lethal encephalitis like Nipah virus. Infection is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. Paramyxovirus viral fusion proteins (F) insert into the target cell membrane, and form a transient intermediate that pulls the viral and cell membranes together as two heptad-repeat regions refold to form a six-helix bundle structure that can be specifically targeted by fusion-inhibitory peptides. Antiviral potency can be improved by sequence modification and lipid conjugation, and by adding linkers between the protein and lipid components. We exploit the uniquely broad spectrum antiviral activity of a parainfluenza F-derived peptide sequence that inhibits both parainfluenza and Nipah viruses, to investigate the influence of peptide orientation and intervening linker length on the peptides’ interaction with transitional states of F, solubility, membrane insertion kinetics, and protease sensitivity. We assessed the impact of these features on biodistribution and antiviral efficacy in vitro and in vivo. The engineering approach based on biophysical parameters resulted in a peptide that is a highly effective inhibitor of both paramyxoviruses and a set of criteria to be used for engineering broad spectrum antivirals for emerging paramyxoviruses.

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confidence: 99%

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confidence: 99%

Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides

Mathieu

Augusto

Niewiesk

et al. 2017

Sci Rep

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“…[30][31][32] These two viruses are leading causes of fatal lower respiratory infections in young children. [33][34][35] A crystal structure of VIQKI co-assembled with HPIV3-HRN revealed a six-helix bundle assembly similar to the HRC/HRN assembly in the post-fusion conformation of the HPIV3 F protein ( Figure 1B). 30 As expected, two distinct conformations were observed within the VIQKI peptide, an α-helix spanning residues corresponding to 457-484 of the F protein, and an extended conformation for residues corresponding to 449-456.…”

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confidence: 93%

Effects of Single α-to-β Residue Replacements on Recognition of an Extended Segment in a Viral Fusion Protein

et al. 2020

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Partial replacement of α-amino acid residues with β-amino acid residues has been established as a strategy for preserving target-engagement by helix-forming polypeptides while suppressing susceptibility to proteolysis. The impact of β-residue incorporation within polypeptides that adopt less regular conformations, however, has received less attention. The HRC domains of fusion glycoproteins from pathogenic paramyxoviruses contain a segment that must adopt an extended conformation in order to engage the HRN domain in the post-fusion state and drive merger of the viral envelope with a target cell membrane. Here we examine the impact of single α-to-β substitutions within this extended N-terminal segment of the engineered HRC peptide VIQKI. Stabilities of helix-bundles formed with a native viral HRN have been evaluated, the structures of five helix-bundles have been determined, and antiviral efficacies have been measured. Many sites within the extended segment show functional tolerance of α-to-β substitution. These results offer a basis for future development of protease-resistant inhibitors of paramyxovirus infection. File list (2) download file view on ChemRxiv Outlaw_VIQKI_beta3_Manuscript.pdf (17.80 MiB) download file view on ChemRxiv Outlaw_VIQKI_beta3_SI.pdf (3.97 MiB) Effects of single α-to-β residue replacements on recognition of an extended segment in a viral fusion protein

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“…Human parainfluenza viruses (HPIVs), either respiroviruses (HPIV1 and HPIV3) or rubulaviruses (HPIV2 and HPIV4), are common causes of significant lower respiratory tract disease including pneumonia. Documented HPIV infection accounts for 30–40% of all acute respiratory tract infections in children [ 1 ]. The zoonotic paramyxovirus Nipah virus (NiV) emerged in the human population from its bat reservoir via pig intermediate hosts, but has now been transmitted directly between humans and represents a global health risk [ 2 ].…”

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confidence: 99%

Antiviral Lipopeptide-Cell Membrane Interaction Is Influenced by PEG Linker Length

et al. 2017

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A set of lipopeptides was recently reported for their broad-spectrum antiviral activity against viruses belonging to the Paramyxoviridae family, including human parainfluenza virus type 3 and Nipah virus. Among them, the peptide with a 24-unit PEG linker connecting it to a cholesterol moiety (VG-PEG24-Chol) was found to be the best membrane fusion inhibitory peptide. Here, we evaluated the interaction of the same set of peptides with biomembrane model systems and isolated human peripheral blood mononuclear cells (PBMC). VG-PEG24-Chol showed the highest insertion rate and it was among the peptides that induced a larger change on the surface pressure of cholesterol rich membranes. This peptide also displayed a high affinity towards PBMC membranes. These data provide new information about the dynamics of peptide-membrane interactions of a specific group of antiviral peptides, known for their potential as multipotent paramyxovirus antivirals.

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Paramyxoviruses: Parainfluenza Viruses

Cited by 8 publications

References 247 publications

Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides

Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides

Effects of Single α-to-β Residue Replacements on Recognition of an Extended Segment in a Viral Fusion Protein

Antiviral Lipopeptide-Cell Membrane Interaction Is Influenced by PEG Linker Length

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