An experimental molecule which stops the HIV from entering cells could pave the way to a new class of HIV inhibitor drugs, suggests a study by US researchers.
A new weapon against the virus would be especially valuable given that resistance to established drug therapies is growing. These mainly target the HIV鈥檚 replication.
The drug, called BMS-378806, successfully halted the HIV-1 virus from penetrating cells in the lab 鈥� this strain infects over 42 million people. It also showed no harmful effects when tested in dogs, rats and monkeys.
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It is one of a new class of HIV drugs with the potential to become a 鈥渧alued addition to our current armamentarium of antiretroviral drugs,鈥� write the team that conducted the study, at Bristol-Myers Squibb in Connecticut. Pin Fang Lin, who led the team, told New 杏吧原创 she is 鈥渃autiously optimistic鈥� about the drug鈥檚 potential in humans.
The molecule could be a 鈥減otent antiretroviral drug鈥� and is a 鈥渕ost promising start鈥� say 脕ine McKnight and Robin Weiss at University College London in the UK, in an editorial accompanying the Proceedings of the National Academy of Sciences paper.
Invading cells
Most current HIV drugs inhibit vital enzymes, called reverse transcriptase and protease, that the virus needs to copy itself. But resistance to these drugs is growing, says the team, with almost 20 per cent of newly diagnosed HIV patients being infected with resistant viruses.
BMS-378806 works by preventing HIV from 鈥渄ocking鈥� with a cell, and then squeezing inside. The molecule attaches itself to a protein on the surface on HIV鈥檚 outer coat that would otherwise dock with a molecule called CD4 on the surface of cells.
Tests in the lab showed 鈥減otent inhibitory鈥� effects against HIV-1, but not HIV-2 or SIV. A two-week study in rats showed the drug could be safely given every day in an oral form. It was also safe in dogs and monkeys.
Importantly, preliminary data showed the drug was effective against HIV strains that were resistant to more conventional drug therapies.
The concept of stopping HIV by interfering with the first stage in its infection process is not new. However, this is the first time this particular docking system has been targeted.
McKnight and Weiss note that the HIV coat protein, called gp120, is one of the better preserved features of the highly changeable virus. HIV鈥檚 ability to rapidly evolve has been the major challenge in the search for a cure.
Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.1832214100)