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Cobalamin inhibition of HIV-1 integrase and integration of HIV-1 DNA into cellular DNA.

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Weinberg JB,Shugars DC,Sherman PA,Sauls DL,Fyfe JA

doi

10.1006/bbrc.1998.8629

subject

Has Abstract

pub_date

1998-05-19 00:00:00

pages

393-7

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(98)98629-6

journal_volume

246

pub_type

杂志文章

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