The search for anti-HBV compounds targeting the unique transcriptional regulatory mechanism of the HBV HBx protein.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08439
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: University of Yamanashi
• Principal Investigator: Yamashita Atsuya 山梨大学, 大学院総合研究部, 助教 (00334871)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: HBV / 転写機構 / 抗HBV化合物

Outline of Final Research Achievements

We established a screening system in order to identify compounds inhibiting the enhancer I/X promoter, which regulates the expression of the hepatitis B virus (HBV) X protein. To identify an antiviral compound targeting the enhancer I/X promoter of HBV, we screened FDA-approved drug library by using this screening system. As a result, 22 primary hit compounds (compounds that inhibit the activity) were obtained. Next, we examined whether the primary hit compounds inhibited the growth of HBV, and obtained four secondary hit compounds. Furthermore, the four secondary hit compounds also inhibited HBV infection and reduced intracellular HBV cccDNA. The results suggest that the enhancer I/X promoter is a potential target site for the development of new therapeutic agents for hepatitis B.

Free Research Field

抗ウイルス薬

Academic Significance and Societal Importance of the Research Achievements

B型肝炎ウイルス（HBV）感染症の治療薬はインターフェロンや核酸アナログ製剤であるが、これらの治療薬は薬剤耐性ウイルスの出現や副作用などの問題あり、継続的な治療が困難なケースがある。また、これらの治療薬では感染者の肝臓に存在するHBV のウイルス遺伝子のHBV cccDNAの完全排除が困難な為、治療後、B型肝炎の症状が収まった後にも、再活性が起こるケースがある。その為、HBV cccDNAが完全排除出来る治療薬の開発が望まれている。従って、本研究の成果からHBV cccDNAの完全排除の治療薬の開発に繋がれば、その社会的な意義は大きなものになると思われる。