Antiviral activity of membrane fusion inhibitors that target gp40 of the feline immunodeficiency virus envelope protein.
For the entry of lentivirus into target cells, fusion between its viral membrane and cellular membrane is essential. The present study was conducted to examine the inhibitory effect of modified peptides corresponding to heptad repeats (HR) 1 and 2 of feline immunodeficiency virus (FIV) envelope gp40 on the fusion between the viral and cellular membranes. FIV-N36 and FIV-C35 were synthesized as authentic peptides of the N-terminal HR1 domain and C-terminal HR2 domain of FIV gp40, respectively. FIV-C35EK1, FIV-C35EK2, and FIV-C35EK3 were peptides synthesized by modifying FIV-C35 as the X-EE-XX-KK concept to increase their solubility in water and the stability of their alpha-helicity. FIV-C35 and FIV-C35EK1 inhibited the cell membrane fusion mediated by FIV-infected cells and the replication of FIV. FIV-N36, FIV-C35EK2, and FIV-C35EK3 did not show any apparent inhibitory effect. These results indicated that the newly developed membrane fusion inhibitors could facilitate the development of novel anti-lentiviral chemotherapies.
Mizukoshi
Fuminori
F
Department of Veterinary Internal Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Baba
Kenji
K
Goto
Yuko
Y
Setoguchi
Asuka
A
Fujino
Yasuhito
Y
Ohno
Koichi
K
Oishi
Shinya
S
Kodera
Yasuyo
Y
Fujii
Nobutaka
N
Tsujimoto
Hajime
H
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002415:Cats; D016181:Feline Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D015726:Giant Cells / Q000821:virology; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006651:Histocytochemistry; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects*
D000998:Antiviral Agents; D006023:Glycoproteins; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C445079:envelope protein, Feline immunodeficiency virus