BioAlliance Pharma, a biopharmaceutical company focused on the field of drug resistance, announced that a research team, including the company, reported preclinical data demonstrating that styrylquinolines (SQs), a new family of inhibitors being developed by BioAlliance, specifically and efficiently inhibit nuclear import of integrase, thereby blocking viral replication of HIV-1 infected cells.
The study suggests a way of combating the emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1). These have arisen through the use of HIV-1 inhibitors such as reverse transcriptase and protease inhibitors. For cell infection to take place, retroviral integration has to occur. This is the process that stably inserts the DNA copy of the viral genomic RNA into the host cell genome.
The process is catalyzed by the HIV integrase enzyme. Prior to this step, this enzyme is involved in the assembly of a stable pre-integration complex required for import of viral DNA across the nuclear cellular envelope. Since integrase has no direct cellular counterpart, it represents an attractive target for the treatment of HIV infection and supports the introduction of integrase inhibitors as a potential weapon in the fight against drug resistant viral strains, BioAlliance Pharma said in a release.
In research reported earlier this year, the research team demonstrated for the first time that integrase targeting molecules might act prior to integration and affect the accumulation of DNA during reverse transcription. In the latest study, the investigators show that SQs block the nuclear import of integrase, suggesting that the inhibition of late cDNA accumulation evidenced in the first paper could be related to a modification of the pre-integration complex activity.
"By demonstrating the inhibiting role of SQs in the nuclear import of viral integrase, the study sheds light on this new family of integrase inhibitors while also pointing towards SQs as a major tool for the identification of the elusive integrase import factor," said Catherine Dargemont, director of Research, the Institut Jacques Monod, Paris, and lead investigator for the study.
"BioAlliance Pharma welcomes the results of this study as it confirms the value of our NCE program and, in this particular case, that our work on styrylquinolines has a promising future," said Dominique Costantini, president and CEO of BioAlliance Pharma.
The research team came from the Institut Jacques Monod, the Ecole Normale Supérieure de Cachan and the Centre National de la Recherche Scientifique (CNRS), as well as BioAlliance Pharma. The study was reported in Molecular Pharmacology (Vol. 66, No. 4: 783-788, 2004).
BioAlliance Pharma is a privately held biopharmaceutical company focused on the development and commercialization of innovative therapeutics and predictive assays in the field of drug resistance, targeting cancer and infectious diseases, including in particular HIV.
The company's lead product within its adhesive technology programme, Miconazole-Lauriad 50 mg Bioadhesive Buccal tablet, is currently in two Phase III trials in Europe for treatment of oropharyngeal candidiasis in cancer and HIV patients.