1. Cobalamin inhibition of HIV-1 integrase and integration of HIV-1 DNA into cellular DNA.
- Author
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Weinberg JB, Shugars DC, Sherman PA, Sauls DL, and Fyfe JA
- Subjects
- Base Sequence, Cells, Cultured, Cobamides pharmacology, DNA Primers genetics, DNA, Viral genetics, DNA, Viral physiology, HIV-1 genetics, HIV-1 physiology, Humans, Hydroxocobalamin pharmacology, In Vitro Techniques, Lymphocytes drug effects, Lymphocytes virology, Monocytes drug effects, Monocytes virology, Polymerase Chain Reaction, Vitamin B 12 analogs & derivatives, DNA, Viral drug effects, HIV Integrase Inhibitors pharmacology, HIV-1 drug effects, Virus Integration drug effects, Vitamin B 12 pharmacology
- Abstract
Our prior studies showed that certain cobalamins inhibit productive HIV-1 infection of primary cultures of blood lymphocytes and monocytes. We demonstrate here that this antiviral activity may be mediated by an inhibition of HIV-1 integrase, an enzyme required for productive infection. Purified recombinant HIV-1 integrase activity was inhibited in vitro by hydroxocobalamin (OH-Cbl), methylcobalamin (Me-Cbl), adenosylcobalamin (Ado-Cbl), and dicyanocobinamide (CN2-Cbi) with IC50 values of approximately 17, 17, 17, and 4 microM, respectively. The agents inhibited HIV-1 infection of cultured monocytes (IC50 values for OH-Cbl, Me-Cbl, Ado-Cbl, and CN2-Cbi of 6, 7, 4, and 1 microM, respectively) and of cultured lymphocytes (IC50 values of 60, 50, 60, and 11 microM, respectively). Experiments using cultured monocytes or lymphocytes demonstrated that OH-Cbl inhibited integration of HIV-1 DNA into cellular DNA. Thus, cobalamins and cobinamides represent novel inhibitors of HIV-1 integrase. These or related agents may be useful as anti-viral treatments that target HIV-1 integrase.
- Published
- 1998
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