Novel antiviral drugs against HIV
The first anti-HIV drug to be approved was a competitive inhibitor of the viral reverse transcriptase (RT) enzyme required for replication. Since then a number of compounds have been developed using the same philosophy, i.e. to prevent HIV from replicating. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent a new family of non-competitive inhibitors that block RT movement thereby inhibiting its activity. Worldwide, the heterosexual route remains the prevalent mode of HIV transmission, necessitating the development of antiviral drugs that could be administered topically, preventing HIV transmission at the mucosa. With this in mind, the EU-funded SHIVA project was designed to develop new NNRTI compounds. The ultimate goal was to produce a specific HIV microbicide for the prevention of sexual transmission/acquisition at the mucosal level that would reach clinical phase I. Project scientists demonstrated that the compound MC1220 was capable of irreversibly knocking out HIV-1 multiplication. Additionally, it showed outstanding biological properties in terms of potency and spectrum of antiretroviral activity against most of the HIV-1 clades responsible for AIDS. Among the achievements of the SHIVA project was the development of an animal model used to test the efficacy of NNRTIs against HIV. At least in part, the above properties of MC1220 were confirmed in the monkey experiments after challenge with the RT-SHIV virus offering over 50 % protection. For testing of MC1220 in the clinic, improved formulations are required to achieve higher protection. Nonetheless, SHIVA members managed to demonstrate the efficacy of NNRTIs in blocking HIV transmission through the mucosal route. Results are encouraging for the ongoing battle against HIV.
