Drug & Device Development

Cyclophilin inhibitor acts against hepatitis C virus

Last Updated: 2006-10-04 16:11:29 -0400 (Reuters Health)

By David Douglas

NEW YORK (Reuters Health) - The cyclophilin inhibitor NIM811 alone, and in combination with alpha interferon, shows strong activity against hepatitis C virus (HCV) in vitro, according to Massachusetts-based researchers.

"We are very excited about this molecule," senior investigator Dr. Kai Lin told Reuters Health. The data "clearly demonstrated NIM811 as a potent HCV inhibitor in vitro and warrant clinical investigation of the compound in hepatitis C patients, which is currently ongoing."

In the September issue of Antimicrobial Agents and Chemotherapy, Dr. Lin and colleagues at the Novartis Institutes for Biomedical Research, Cambridge note that cyclosporine binds to a family of cellular proteins, the cyclophilins, and thus inhibits HCV replication in vitro.

In a series of studies, the researchers found that N1M811 binds to cyclophilins with higher affinity than cyclosporines, and they also observe that "is devoid of the significant immunosuppressive activity associated with cyclosporine."

Moreover, use of the agent along with alpha interferon enhanced anti-HCV activity without any increase in cytotoxicity.

Thus, concluded Dr. Lin, "the compound, with a unique mechanism of action targeting host factors, provides an opportunity for combination therapy, the principle of which has also been demonstrated in our in vitro study."

Antimicrob Agents Chemother 2006;50:2976-2982.