Antiviral mechanism of new endoperoxide compounds showing antimalarial activity

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15142
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Okayama University
• Principal Investigator: Kato Nobuyuki 岡山大学, 医歯薬学総合研究科, 教授 (40150883)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: ウイルス / 感染症 / 微生物 / 抗ウイルス剤 / 薬理作用機序 / 遺伝子解析 / マイクロアレイ解析

Outline of Final Research Achievements

We have carried out the study to clarify the anti-hepatitis C virus (HCV) mechanism of new anti-HCV compounds (N-89 and its derivative N-251). From N-89- or N-251-sensitive HCV-RNA-replicating cells (sensitive cells), we first established the cell lines possessing a N-89- or N-251-resistant phenotype (resistant cells). Using the sensitive and resistant cells, we analyzed the action mechanism of these compounds. The results appeared that both host and viral factors contribute to almost the same degree of the resistance to these compounds. Genetic analysis of HCVs derived from the resistant cells detected amino acids substitutions, which might be involved in the acquisition of resistance against these compounds. cDNA microarray analysis selected gene candidates, which might contribute to resistant acquisition. In addition, we demonstrated that these compounds showed antiviral effects against Japanese encephalitis virus, hepatitis B virus, and hepatitis E virus.

Free Research Field

ウイルス学、細胞生物学、分子生物学、肝臓学