Evaluation of the inactivation of infectious Herpes simplex virus by host-defense peptides.
A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide microplate assay was adapted to screen for the ability of 20 host-defense peptides to inactivate herpes simplex virus type 1 and type 2. The procedure required minimal amounts of material, was reproducible, and was confirmed with standard antiviral testing techniques. In screening tests, with the exception of melittin, a highly cytotoxic and hemolytic peptide found in bee venom, the alpha-helical peptides in our test panel (magainins, cecropins, clavanins, and LL-37) caused little viral inactivation. Several beta-sheet peptides (defensins, tachyplesin, and protegrins) inactivated one or both viruses, sometimes with remarkable selectivity. Two peptides were identified as having antiviral activity against both viruses, indolicidin (a tryptophan-rich peptide from bovine neutrophils) and brevinin-1 (a peptide found in frog skin). The antiviral activity of these two peptides was confirmed with standard antiviral assays. Interestingly, the antiviral activity of brevinin-1 was maintained after reduction and carboxamidomethylation, procedures that abolished its otherwise prominent hemolytic and cytotoxic effects.
Yasin
B
B
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, CA 90095-1731, USA.
Pang
M
M
Turner
J S
JS
Cho
Y
Y
Dinh
N N
NN
Waring
A J
AJ
Lehrer
R I
RI
Wagar
E A
EA
D000595:Amino Acid Sequence; D029845:Amphibian Proteins; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents / Q000494:pharmacology*; D002417:Cattle; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D010948:Viral Plaque Assay
D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D010455:Peptides; C073143:indolicidin; C078413:brevinin-1 protein, Rana