2021 Fiscal Year Final Research Report

Development of therapeutics for intractable infections using diverse natural products combined with stress-inductive biosynthesis and chemical modification

Research Project

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Project/Area Number	19H03701
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 54030:Infectious disease medicine-related
Research Institution	Tohoku University
Principal Investigator	Kodama Eiichi 東北大学, 災害科学国際研究所, 教授 (50271151)
Co-Investigator(Kenkyū-buntansha)	林宏典東北大学, 災害科学国際研究所, 助教 (00752916) 浅井禎吾東北大学, 薬学研究科, 教授 (60572310) 菊地晴久慶應義塾大学, 薬学部(芝共立), 教授 (90302166)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	ウイルス学 / 薬学 / 感染症 / 天然物 / 化学合成
Outline of Final Research Achievements	Molecular and structural diversities of natural compound have been required to expand for drug development. Here, we produced novel natural derivatives by the biosynthetic pathway remodeled by genome mining technology and identified novel anti-HIV agent. We established a simple and rapid screening method to develop antiviral agents against adenovirus, which caused epidemic keratoconjunctivitis. Additionally, we also identified several novel classes of antibacterial agents, which blocked uridine kinase, thymidine synthetase and serine hydroxymethyl transferase. Moreover, anti-viral and -bacterial mechanisms of compounds we identified were analyzed by time-of-addition method and crystal structural analysis. These results are important not only to expand molecular and structural diversities of natural compounds but also to develop therapeutic agents against antimicrobial resistances, unpredictable outbreaks and wildly destructive health consequences.
Free Research Field	ウイルス学
Academic Significance and Societal Importance of the Research Achievements	本研究における天然物の生合成経路を人工的に拡張させる手法は、現在、創薬分野で問題となっている化合物の多様性枯渇に対する有効な解決手段となる。新規作用機序を持つ抗HIV薬や抗菌薬の新規標的タンパクの同定といった研究成果は、薬剤耐性を有する微生物に対する新薬開発の発展に資する。流行性角結膜炎の原因となるアデノウイルスに対して簡便かつ迅速に治療薬候補の同定が可能となるスクリーニング系を開発した。化合物ライブラリーの多様化、標的タンパクの同定、スクリーニング系の開発や治療薬候補化合物の同定など本研究成果は重要な創薬基盤であり、将来、パンデミックを起こし得る新興・再興感染症への対策に資する。