Hepatitis B virus (HBV) infection is a serious global health problem. Approximately 2 billion people have been infected worldwide and 400 million suffering from chronic HBV infection. The current standard therapies, mainly interferon and nucleoside analogues, are limited by their efficacy and viral resistance, therefore the demand for new anti-HBV drug is still high.

The research team led by Professors NAN Fajun  and  ZUO Jianping from Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, has been identifying novel agents from natural product-based synthetic compound libraries for anti-HBV therapy following more than 7 years' endeavors. Through SAR studies and hit optimizations, the team has identified a novel non-nucleoside anti-HBV drug candidate, isothiafludine (known as NZ-4 or W28F). SIMM has filed the patent applications in 8 major countries and areas including China, US, Europe and Japan. On March 5th, 2012, the first-in-class anti-HBV drug, isothiafludine and its capsule, has been approved by State Food and Drug Administration (SFDA) for Phase I clinical trial.

With novel anti-HBV replication mechanism, isothiafludine has demonstrated potent anti-viral activity both in vivo and in vitro. In addition, isothiafludine has shown inhibition effect against the nucleoside resistant HBV virus which means that it could potentially provide new therapy to the nucleoside resistant patients. The clinical trial is carried out by Shanghai HaiHe Pharmaceutical Co., Ltd., founded jointly by SIMM and Shanghai Zhangjiang Science & Technology Venture Captical.