Viral infection is the basis of most liver cancer and all cervical cancer. The best way to attack these cancers is by attacking the virus. The major focus of the Zlotnick lab is Hepatitis B Virus. More than 360 million people suffer from chronic HBV, more than 1 million in the US. Worldwide, HBV contributes to nearly 1 million deaths each year. It is the leading cause of hepatocellular carcinoma. Though there is an excellent vaccine, it is not therapeutic and some strains of HBV are insensitive to it. The current HBV antivirals focus on a single target, do not "cure" the patient, and lead to a life-threatening viral rebound if the patient is removed from therapy. There is a real need for a better therapeutics that have a chance of clearing the virus, a lower propensity to select for mutations, and do not lead to viral rebound. We have shown that the process of assembling HBV particles is a suitable antiviral target, engendering specificity and efficacy. Our focus is on target identification and molecular design. Our best compounds are effective in the nM concentration range. In collaboration, putative antivirals are tested in culture, and eventually in animals. We continue to identify new antivirals and on develop the best molecules that we now have in hand. We also study assembly of a structural relative of human papilloma virus and collaborated with Merck to examine assembly of a component of the Gardasil HPV vaccine.
