Researchers at the University of Alabama at Birmingham have reported that a set of novel methylenecyclopropane (MCP) nucleoside analogs, synthesized by Microbiotix, Inc., have shown increased activity against a broad spectrum of human herpesviruses. The new agents are derivations of the compound cyclopropavir (CPV), currently in human phase I clinical studies, which has previously been shown to exhibit good antiviral activity against human beta-and gamma-herpes viruses, including HCMV, EBV, HHV-6A, HHV-6B, and HHV-8. In addition, all but one of the new analogs had potent anti-viral activity against HHV-6B that was greater than that of cidofovir (CDV).
Furthermore, some of the new analogs have demonstrated an even broader spectrum of anti-herpes activity, with significant inhibition of the alpha-herpes viruses HSV-1, HSV-2, and VZV as well. The group also reports that the antiviral activity of these new compounds appears to be less dependent on HCM UL97 kinase activity than ganciclovir and CPV, and largely unaffected by the level of HSV thymidine kinase activity. These results suggest that the mechanism of antiviral action is distinct from that of CPV.
Terry Bowlin, Ph.D., CEO of Microbiotix, Inc, serves as the Principal Investigator of the NIH funded study. “These new MCP nucleoside analogs represent an exciting new broad spectrum approach to treating human herpes viruses, including HHV-6.” said Dr. Bowlin. The project is currently funded through a Phase II Small Business Innovation Research (SBIR) grant from the National Institutes of Health/NIAID, which was awarded in 2012 to “develop a novel series of purine nucleoside analogs for therapeutic efficacy against emerging infectious disease agents HHV-6 and HHV-8” (see Press Release for original SBIR Phase I award). Microbiotix, Inc. is a biopharmaceutical company focused on the discovery and development of drugs to target serious infectious diseases. The results in this publication are a result of the company’s innovative drug discovery program to identify agents for use in areas with significant unmet medical needs, such as the field of HHV-6.
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