9-(2-Phosphonylmethoxyethyl)adenine (PMEA) effectively inhibits retrovirus replication in vitro and simian immunodeficiency virus infection in rhesus monkeys.
9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is a potent and selective inhibitor of the in vitro replication of a number of retroviruses, including HIV-1 and HIV-2, simian immunodeficiency virus (SIV), simian AIDS-related virus (SRV), feline immunodeficiency virus (FIV) and Moloney murine sarcoma virus (MSV). PMEA causes a dose-dependent suppression of the induction of anti-SIVmacgp120 antibodies in SIV mac-infected rhesus monkeys. Complete suppression of anti-SIVmacgp120 antibodies was achieved in SIV-infected animals treated with PMEA at 2 x 10 or 2 x 5 mg/kg per day for 29 days. No toxic side-effects were noted during this treatment period. Antibodies against SIVmac gp120 appeared 1-2 weeks after PMEA treatment was stopped, but the antibody titre reached in these animals was significantly lower than in the SIVmac-infected animals who had not been treated with PMEA. Our data strongly suggest that PMEA should be pursued for its potential in the treatment of AIDS and other retrovirus infections.
Balzarini
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Naesens
L
L
Slachmuylders
J
J
Niphuis
H
H
Rosenberg
I
I
Holý
A
A
Schellekens
H
H
De Clercq
E
E
D000225:Adenine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D006801:Humans; D008253:Macaca mulatta; D008562:Membrane Glycoproteins; D015394:Molecular Structure; D063065:Organophosphonates; D012190:Retroviridae / Q000187:drug effects* / Q000502:physiology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D014018:Tissue Distribution; D014759:Viral Envelope Proteins; D014779:Virus Replication
D000914:Antibodies, Viral; D000998:Antiviral Agents; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D063065:Organophosphonates; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus; C053001:adefovir; D000225:Adenine