Antiviral efficacy in vivo of the anti-human immunodeficiency virus bicyclam SDZ SID 791 (JM 3100), an inhibitor of infectious cell entry.
SID 791, a bicyclam inhibiting human immunodeficiency virus (HIV) replication in vitro by blocking virus entry into cells, is an effective inhibitor of virus production and of depletion of human CD4+ T cells in HIV type 1-infected SCID-hu Thy/Liv mice. Steady levels of 100 ng of SID 791 or higher per ml in plasma resulted in statistically significant inhibition of p24 antigen formation. Daily injections of SID 791 caused a dose-dependent decrease in viremia, and this inhibition could be potentiated by coadministration of zidovudine or didanose. The present study suggests that SID 791 alone or in combination with licensed antiviral agents may decrease the virus load in HIV-infected patients and, by extension, that the infectious cell entry step is a valid target for antiviral chemotherapy of HIV disease. The SCID-hu Thy/Liv model in effect provides a rapid means of assessing the potential of compounds with novel modes of antiviral action, as well as the potential of antiviral drug combinations.
Datema
R
R
Sandoz Research Institute, Vienna, Austria.
Rabin
L
L
Hincenbergs
M
M
Moreno
M B
MB
Warren
S
S
Linquist
V
V
Rosenwirth
B
B
Seifert
J
J
McCune
J M
JM
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001596:Benzylamines; D016516:CD4-CD8 Ratio / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D000080027:Cyclams; D016049:Didanosine / Q000494:pharmacology; D004343:Drug Implants; D015658:HIV Infections / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D000998:Antiviral Agents; D001596:Benzylamines; D000080027:Cyclams; D004343:Drug Implants; D006571:Heterocyclic Compounds; D015215:Zidovudine; D016049:Didanosine; C088327:plerixafor