In vitro synergistic activity against CCR5-tropic HIV-1 with combinations of potential candidate microbicide molecules HHA, KRV2110 and enfuvirtide (T20)
| Autor: | Dominique Schols, Mohammad-Ali Jenabian, Jong Chan Son, Yven Van Herrewege, Guido Vanham, Héla Saïdi, Charlotte Charpentier, Jan Balzarini, Laurent Bélec |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Microbiology (medical) Enfuvirtide Efficacy Anti-HIV Agents Cell Survival Microbial Sensitivity Tests Viral diseases Cell Line HeLa Young Adult Microbicide Liliaceae medicine Humans Pharmacology (medical) Viability assay Evaluation Cells Cultured Pharmacology Infectivity Dose-Response Relationship Drug biology Reverse-transcriptase inhibitor Vaginal microbicide Transmission prevention Drug Synergism Tolerability biology.organism_classification Virology HIV Envelope Protein gp41 Peptide Fragments In vitro Microbicides Vaginal AIDS Infectious Diseases HIV-1 Combinations Plant Lectins medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 64:1192-1195 |
| ISSN: | 1460-2091 0305-7453 |
| Popis: | OBJECTIVES: To block the different mechanisms of HIV mucosal transmission, it is likely that use of several microbicide molecules will lead to the best protection against HIV transmission. Indeed, the combination of microbicides with complementary mechanisms of action is expected to increase the antiviral potency of the formulation. METHODS: The gp120-interacting plant lectin HHA ('Hippeastrum hybrid agglutinin'), the non-nucleoside reverse transcriptase inhibitor KRV2110 and the fusion inhibitor enfuvirtide (T20) were combined in 12 drug associations by using the Ray combination design method. Their activity against HIV-1(BaL) was assessed by the lymphocyte infectivity reduction assay and by the single-cycle BaL pseudovirus (PV) assay. In addition, their cell tolerance was evaluated for HEC-1 and HeLa epithelial cell lines, both originating from genital tissue. RESULTS: All evaluated combinations showed synergistic activity in both lymphocyte infectivity reduction and single-cycle BaL PV assays. The combination HHA + KRV2110 resulted in the highest cell viability, whereas the combinations including T20 exhibited a dose-dependent decrease in cell viability, demonstrating the differential tolerance of epithelial cell lines to the combinations. CONCLUSIONS: These observations provide a rational basis for in vitro testing of microbicide candidate molecule combinations, including anti-HIV-1 and cytotoxic cellular assays. |
| Databáze: | OpenAIRE |
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