A Novel Peptide Derived from the Fusion Protein Heptad Repeat Inhibits Replication of Subacute Sclerosing Panencephalitis Virus In Vitro and In Vivo.
Subacute sclerosing panencephalitis (SSPE) is a persistent, progressive, and fatal degenerative disease resulting from persistent measles virus (MV) infection of the central nervous system. Most drugs used to treat SSPE have been reported to have limited effects. Therefore, novel therapeutic strategies are urgently required. The SSPE virus, a variant MV strain, differs virologically from wild-type MV strain. One characteristic of the SSPE virus is its defective production of cell-free virus, which leaves cell-to-cell infection as the major mechanism of viral dissemination. The fusion protein plays an essential role in this cell-to-cell spread. It contains two critical heptad repeat regions that form a six-helix bundle in the trimer similar to most viral fusion proteins. In the case of human immunodeficiency virus type-1 (HIV-1), a synthetic peptide derived from the heptad repeat region of the fusion protein enfuvirtide inhibits viral replication and is clinically approved as an anti-HIV-1 agent. The heptad repeat regions of HIV-1 are structurally and functionally similar to those of the MV fusion protein. We therefore designed novel peptides derived from the fusion protein heptad repeat region of the MV and examined their effects on the measles and SSPE virus replication in vitro and in vivo. Some of these synthetic novel peptides demonstrated high antiviral activity against both the measles (Edmonston strain) and SSPE (Yamagata-1 strain) viruses at nanomolar concentrations with no cytotoxicity in vitro. In particular, intracranial administration of one of the synthetic peptides increased the survival rate from 0% to 67% in an SSPE virus-infected nude mouse model.
Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
Masahiro
M
Watanabe
Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
Koichi
K
Hashimoto
Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
Yusaku
Y
Abe
Division of Emerging Infectious Diseases, Tohoku University School of Medicine, Sendai, Japan.
Eiichi N
EN
Kodama
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Ryota
R
Nabika
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Shinya
S
Oishi
Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
Shinichiro
S
Ohara
Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
Masatoki
M
Sato
Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
Yukihiko
Y
Kawasaki
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Nobutaka
N
Fujii
Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
Mitsuaki
M
Hosoya
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D008459:Measles virus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020449:Repetitive Sequences, Amino Acid; D013344:Subacute Sclerosing Panencephalitis / Q000473:pathology / Q000821:virology; D013997:Time Factors; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D010455:Peptides; D014760:Viral Fusion Proteins