Anti-(human immunodeficiency virus) activity of polyoxotungstates and their inhibition of human immunodeficiency virus reverse transcriptase.
Heteropolyoxotungstates of the Keggin class containing different heteroatoms were tested for inhibition of two strains of human immunodeficiency virus 1 (HIV-1); they exhibited varying antiviral activity. Compounds containing boron were inactive, only one of those containing phosphorus showed selective anti-viral activity, whereas all silicon-containing compounds exhibited significant anti-viral activity in C8166 cells infected with the IIIB strain. Their effectiveness was some 10-fold higher in JM cells with selectivity indices of about 2000. The silicotungstates were effective inhibitors of HIV reverse transcriptase, showing greater inhibition with RNA/DNA template primers than with DNA/DNA template.primer. Kinetic analysis demonstrated that they inhibit the enzyme by different mechanisms, as, of the four compounds examined, two competed with template.primer and two competed with deoxynucleoside triphosphate. Inhibition of DNA polymerase activity by these compounds was compared using polymerases from different sources, including human; although not necessarily most specific for HIV-1 reverse transcriptase, they did not inhibit all DNA polymerases to a similar degree.
Moore
P S
PS
Medical Research Council, Collaborative Centre, Mill Hill, London, U.K.
Jones
C J
CJ
Mahmood
N
N
Evans
I G
IG
Goff
M
M
Cooper
R
R
Hay
A J
AJ
D000998:Antiviral Agents / Q000494:pharmacology*; D001895:Boron / Q000494:pharmacology; D017931:DNA Primers; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D015195:Drug Design; D016655:HIV Core Protein p24 / Q000032:analysis; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D007700:Kinetics; D019384:Nucleic Acid Synthesis Inhibitors; D010758:Phosphorus / Q000494:pharmacology; D012313:RNA; D018894:Reverse Transcriptase Inhibitors; D017655:Silicon Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013698:Templates, Genetic; D017973:Tungsten Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D017931:DNA Primers; D016655:HIV Core Protein p24; D019384:Nucleic Acid Synthesis Inhibitors; C034477:RNA primers; D018894:Reverse Transcriptase Inhibitors; D017655:Silicon Compounds; D017973:Tungsten Compounds; D010758:Phosphorus; D012313:RNA; D054303:HIV Reverse Transcriptase; D012321:DNA-Directed RNA Polymerases; D001895:Boron