Less than six years on, scientists are well on the way down a path to a cure. Almost 50 therapies are now in clinical trials, and many more will soon follow.
To the virus’s polymerase enzyme, nucleoside analogues look like any other genetic building block, ready to be incorporated into DNA as required to copy the virus — but they’re not. Once the imposter molecule gets into a growing strand of viral DNA, replication grinds to a halt, and viral growth is markedly blunted.
Zlotnick suspects that vebicorvir was not potent enough to fully prevent virus production. He hopes that next-generation CAMs now in early clinical testing might do better. Still, results from the vebicorvir trial have forced him and others to rethink their approach. Antiviral drugs directed at a few crucial proteins might have been able to wipe out hepatitis C.
These RNA-blocking strategies, which include both antisense therapies and small interfering RNA molecules, have produced dramatic results, often driving down indicators of HBV infection quickly and durably.
“That helps to focus the response on the right antigens,” says Mala Maini, a viral immunologist at University College London. “But then it may need to be combined with some other approaches,” she adds, such as checkpoint-blocking molecules, common in cancer treatment, that help to lift the brakes on T-cell activity.