Antiviral activity of an immunomodulatory lipophilic desmuramyl dipeptide analog.
BCH-527, the lipophilic hydrochloride salt of octadecyl D-alanyl L-glutamine, was evaluated for efficacy against experimentally induced murine cytomegalovirus (MCMV), influenza A (H1N1) (IV-A), and Punta Toro virus (PTV) infections in mice. The compound was administered i.p. every other day for a total of 4 injections commencing 24 h previrus exposure. Doses ranged from 12.5 to 200 mg/kg per injection in the various experiments. The MCMV infection was significantly inhibited in two experiments by doses of 25-200 mg/kg, as manifested by increased numbers of survivors and decreased titers of virus recoverable from tissues. The IV-A infection was weakly inhibited, with antiviral activity seen in lowered lung scores and lung weights and less decline in arterial oxygen saturation values. The PTV infection was not inhibited. BCH-527 was stimulatory to cytotoxic T-cells, natural killer (NK) cells, macrophages, and splenic B-cells. The highest dose tested, 200 mg/kg, was inhibitory to cytotoxic T-cell activity and to some extent to NK cell and macrophage activity. These data suggest BCH-527 functions as an immune modulator in exerting the observed antiviral activity.
Sidwell
R W
RW
Institute for Antiviral Research, Utah State University, Logan 84322-5600, USA.
Smee
D F
DF
Huffman
J H
JH
Bailey
K W
KW
Warren
R P
RP
Burger
R A
RA
Penney
C L
CL
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D005260:Female; D006566:Herpesviridae Infections / Q000188:drug therapy* / Q000276:immunology; D009980:Influenza A virus; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D018146:Muromegalovirus; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D004151:Dipeptides; C094454:octadecyl alanylglutamate hydrochloride