(-)-2'-deoxy-3'-thiacytidine is a potent, highly selective inhibitor of human immunodeficiency virus type 1 and type 2 replication in vitro

Abstract

The (-)-enantiomer of 2'-deoxy-3'-thiacytidine (3TC) was found to be a potent and selective inhibitor of human immunodeficiency virus types 1 (HIV-1) and 2 (HIV-2) in vitro. We determined its antiviral activity against a number of laboratory strains of HIV-1 and HIV-2 in a range of CD4-bearing lymphocyte cell lines (mean 50% inhibitory concentration [IC50] range, 4 nM to 0.67 microM). 3TC was also active against a range of HIV-1 strains in peripheral blood lymphocytes (mean IC50 range, 2.5 to 90 nM). The IC50 for cytotoxicity in seven lymphocyte cell cultures, including human peripheral blood lymphocytes, ranged from 0.5 to 6 mM. 3TC had no detectable antiviral activity against a range of other viruses or in cells chronically infected with HIV-1 or HIV-2. The effects of time of addition of the compound and varying the multiplicity of infection on the antiviral activity of 3TC were determined. The results showed that 3TC is a potent and selective inhibitor of HIV-1 and HIV-2 replication in vitro.

Dynamics and Consequences of IL-21 Production in HIV-Infected Individuals: A Longitudinal and Cross-Sectional Study

“…5B). To determine whether HIV replication was necessary for decreased IL-21 production, we infected PBMCs with and without 3TC; a nucleoside reverse transcriptase inhibitor known to block viral replication (31). The treatment with 3TC restored IL-21 production in the cell culture supernatants (p , 0.01) as well as + T cells were isolated from human PBMCs after 72 h activation with PHA (10 mg/ml) and IL-2 (100 U/ml).…”

Human APOBEC3G-Mediated Editing Can Promote HIV-1 Sequence Diversification and Accelerate Adaptation to Selective Pressure

“…The use of the nucleoside analog RT inhibitor (Ϫ)2Ј,3Ј-dideoxy-3Ј-thiacytidine (3TC) imposes strong selection for a single amino acid substitution in the conserved Tyr-Met-Asp-Asp motif of the catalytic site of RT. High-level resistance is typically conferred by amino acid substitutions that change the methionine at position 184 to isoleucine (M184I), valine (M184V), or threonine (M184T) (3,4). When 3TC is used as a single drug for people infected with HIV-1, drug-resistant virus outcompetes wild-type virus within a few weeks (3), suggesting that the required sequence changes commonly preexist in the virus population.…”

Synthesis of 4′-Thionucleosides as Antitumor and Antiviral Agents

“…39) Indeed, the L-isomer of lamivudine was more potent and less cytotoxic than its D-isomer. [40][41][42][43] We concluded that our synthetic approach was effective. Adopting a similar synthetic scheme for the D-isomers depicted above, we were able to obtain L-4′-thioarabinonucleosides from D-xylose by shifting the chiral carbons employed.…”