Antiviral activity of amodiaquine derivatives against SFTSV

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04084
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Kagoshima University
• Principal Investigator: BABA MASANORI 鹿児島大学, 総合科学域総合研究学系, 教授 (70181039)
• Co-Investigator(Kenkyū-buntansha): 西條 政幸 国立感染症研究所, ウイルス第一部, 部長 (50300926)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: SFTSV / 抗ウイルス薬 / アモジアキン

Outline of Final Research Achievements

We have previously found that the anti-malaria agent amodiaquine is active against the replication of severe fever with thrombocytopenia syndrome virus (SFTSV). When the anti-SFTSV activity of 100 amodiaquine derivatives was examined, a novel derivative (# 90) was identified as a potent and selective inhibitor of SFTSV in vitro. Its antiviral activity was approximately 10-fold higher than that of amodiaquine. When its mechanism of action was studied, # 90 was appeared to act on a rather early event in the viral replication cycle and exert its anti-SFTSV activity. When # 90 and favipiravir was combined, it exhibited an additive antiviral effect. The results of mouse experiments revealed that # 90 had a problem of its pharmacokinetics, suggesting that its formulation change or chemical modification will be required.

Free Research Field

ウイルス学・化学療法学

Academic Significance and Societal Importance of the Research Achievements

重症熱性血小板減少症候群（SFTS）はマダニによって媒介される致死的なウイルス感染症である。現時点での治療は対症療法しかなく，有効なワクチンや抗ウイルス薬は存在しない。従って，SFTS に対する有効な治療薬に関する研究は学術的にも社会的にも大きな意義があると思われる。さらに，本研究で同定した新規アモジアキン誘導体は強いエボラウイルスに対する増殖抑制効果を示すことが分かっている。そこで，ボストン大学の Robert Davey 教授のグループと新規アモジアキン誘導体の抗エボラ薬としての開発に向けた国際共同研究を開始している。