title: Heptad repeat-derived peptides block protease-mediated direct entry from the cell surface of severe acute respiratory syndrome coronavirus but not entry via the endosomal pathway.
abstract: The peptides derived from the heptad repeat (HRP) of severe acute respiratory syndrome coronavirus (SCoV) spike protein (sHRPs) are known to inhibit SCoV infection, yet their efficacies are fairly low. Recently our research showed that some proteases facilitated SCoV's direct entry from the cell surface, resulting in a more efficient infection than the previously known infection via endosomal entry. To compare the inhibitory effect of the sHRP in each pathway, we selected two sHRPs, which showed a strong inhibitory effect on the interaction of two heptad repeats in a rapid and virus-free in vitro assay system. We found that they efficiently inhibited SCoV infection of the protease-mediated cell surface pathway but had little effect on the endosomal pathway. This finding suggests that sHRPs may effectively prevent infection in the lungs, where SCoV infection could be enhanced by proteases produced in this organ. This is the first observation that HRP exhibits different effects on virus that takes the endosomal pathway and virus that enters directly from the cell surface.
authors.affiliation: Department of Virology III, National Institute of Infectious Disease, Gakuen 4-7-1, Musashi-murayama, Tokyo 208-0011, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ujike
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Otaka
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kodama
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Taguchi
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000821:virology; D010447:Peptide Hydrolases / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology*; D014709:Vero Cells; D014764:Viral Proteins / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D010455:Peptides; D014764:Viral Proteins; D010447:Peptide Hydrolases