Over 30 million people globally are estimated to be infected with HIV. The only means to reduce virus transmission and replication is prevention and antiretroviral (ARV) drugs. Currently, there are 27 licensed drugs that interfere with the normal function of HIV enzymes that are key for viral replication in infected cells. The inherent ability of the virus to mutate its enzymes and escape immune attack has resulted in the emergence of drug-resistant strains. This clearly necessitates the continuous development of new drugs with a completely different mode of action. In this context, the EU-funded HIVINNOV (Generation of a new class of antiretrovirals targeting HIV-cellular cofactors interactions) project proposed a new class of ARV drugs that specifically target virus–host interaction. Scientists based their strategy on two molecules, cofactors of the integrase enzyme and capsid protein (CA). Partners have contributed significantly to the discovery of these cofactors and the elucidation of their importance in the HIV life cycle. Small molecules that inhibit the integrase–LEDGF interaction have been developed and exhibit high ARV activity. Results indicated that these molecules affect the integration of the virus in target cells and during production of infectious particles. The molecules were in vivo validated for this new class of ARV in the humanised mouse model of HIV infection. Researchers delineated the structure of the cofactor Transportin-SR2 and identified compounds capable of blocking its interaction with CA. Promising hits have been obtained and these molecules are under investigation for their antiviral capability. Importantly, partners discovered a new role of the heat shock protein (Hsp90) in the control of HIV reactivation from latency. They also established the suitability of the NGS-HIS mouse model of HIV for the validation of anti-HIV drug efficiency during oral drug administration. HIVINNOV's new generation of antiviral drugs promises to overcome the current resistance problems associated with HIV treatment. Equally significant is the consortium's contribution to drug release in the countries that actively participate in phase II trials.
Anti-HIV drug, drug-resistant strain, HIVINNOV, virus-host interaction, integrase, transportin