Journal article
Cooperative inhibition of HIV-1 by drug combinations containing the biguanide-based inhibitor NB325
Journal of neurovirology, Vol.13, pp.114-114
01 Jan 2007
Abstract
Combination antiretroviral therapy (ART), which continues to be used as highly effective treatment of HIV-1-associated immunopathogenesis, has also had a positive impact on neurologic disease caused by HIV-1 infection of the central nervous system (CNS). However, limits on treating or preventing HIV-1-associated neuropathogenesis due to reduced CNS drug penetration and drug-associated neurologic side effects underscore the importance of developing new drugs and combinations with greater efficacy. Our efforts in this direction have focused on NB325, which is a biguanide-based compound that is an effective inhibitor of both R5 and X4 strains of HIV-1. Assays of drug combinations have demonstrated that NB325 can be cooperatively paired with several types of HIV-1 inhibitors, including nonnucleoside and nucleoside reverse transcriptase inhibitors (efavirenz and tenofovir, respectively), and a fusion inhibitor (cyanovirin). Assays of cytotoxicity and anti-HIV?1 activity demonstrated that these compound combinations were minimally cytotoxic and highly effective against HIV-1 entry and replication. Further analyses demonstrated additive or synergistic activity against HIV-1, and that the nature of the activity was dependent on the partner for NB325 and the combination ratio, as confirmed through the use of two distinctly different software programs-CalcuSyn and MacSynergy II - that are used specifically to analyze activities of combined agents. These results suggest that cooperative antiviral activity between two agents may be influenced by similarities or differences between each agent's mechanism of action. Furthermore, these results support the further testing of combinations that may be used effectively to treat HIV-1 CNS infection.
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Details
- Title
- Cooperative inhibition of HIV-1 by drug combinations containing the biguanide-based inhibitor NB325
- Creators
- V PirroneS PassicT Kish-CataloneB WigdahlR RandoM LabibF Krebs
- Publication Details
- Journal of neurovirology, Vol.13, pp.114-114
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170559504721