Discovery Of Anti-HBV Drug Targets Based On Molecular Interaction Network

Hepatitis B virus (HBV) is well known as the major causative agent of human hepatitis in China. Approximate 80% of carriers have different levels of hepatocyte destruction, and most of them transfer to serious consequences progressively: liver cirrhosis and hepatocellular carcinoma (HCC). HBV is the target of most drugs developed so far, but HBV genome which is relatively small encode limited potential targets, which limited the development of anit-HBV drugs and resulted virus mutation and drug resistance easily, making lasting therapy impossible. In this article, we set about from viral infection in host, and inferred the key factors of host in the process of infection and their drugability basing on molecular interaction network between host and virus.We implemented flexible pathway queries and analysis through constructing HBVPathDB database including HBV infection related molecular interaction pathway. Based on HBVPathDB and HBV related gene expression data, the key pathways and molecules were found though the recursive correlation analyse, and we proofed our discovery in the HepG2.2.15 cell line.Defender against death 1 (DAD1) and fibronectin (Fn) play a key role in HBV infection and replication, and DAD1 can regulate the expression of fibronectin. Thio-FN and Thio-DAD1 antisense oligonucleotides which showed not overt toxicity to Hep2.2.15 proliferation can inhibit the secrection of HBeAg, HBsAg and HBV DNA in the Hep2.2.15 cell line effectively, and it indicates that Fn and DAD1 have fine drugability.To sum up, Fn and DAD1 as the key molecules in HBV infection and replication can be the targets of anti-HBV drugs.