Identification of a dendrimeric heparan sulfate-binding peptide that inhibits infectivity of genital types of human papillomaviruses.
Peptide dendrimers consist of a peptidyl branching core and/or covalently attached surface functional units. They show a variety of biological properties, including antiviral activity. In this study, a minilibrary of linear, dimeric, and dendrimeric peptides containing clusters of basic amino acids was evaluated for in vitro activity against human papillomaviruses (HPVs). The peptide dendrimer SB105-A10 was found to be a potent inhibitor of genital HPV types (i.e., types 16, 18, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 2.8 and 4.2 μg/ml (0.59 and 0.88 μM), and no evidence of cytotoxicity was observed. SB105-A10 interacts with immobilized heparin and with heparan sulfates exposed on the cell surface, most likely preventing virus attachment. The findings from this study indicate SB105-A10 to be a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections.
Donalisio
Manuela
M
Department of Clinical and Biological Sciences, University of Turin, S Luigi Gonzaga Hospital, Regione Gonzole 10, 10043 Orbassano, Turin, Italy.
Rusnati
Marco
M
Civra
Andrea
A
Bugatti
Antonella
A
Allemand
Donatella
D
Pirri
Giovanna
G
Giuliani
Andrea
A
Landolfo
Santo
S
Lembo
David
D
D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D016466:CHO Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D050091:Dendrimers / Q000737:chemistry*; D006367:HeLa Cells; D006497:Heparan Sulfate / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D046529:Microscopy, Electron, Transmission; D027383:Papillomaviridae / Q000187:drug effects* / Q000472:pathogenicity*; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D020349:Surface Plasmon Resonance
D000998:Antiviral Agents; D050091:Dendrimers; D006497:Heparan Sulfate; D010455:Peptides