Development of anti-adenovirus agents with carbocyclic nucleosides via a novel assay

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17934
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: International University of Health and Welfare
• Principal Investigator: Konno Kiju 国際医療福祉大学, 薬学部, 助教 (50807493)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 核酸化学 / 医薬品化学 / 抗ウイルス剤 / アデノウイルス

Outline of Final Research Achievements

To develop antiviral agents against adenovirus infections, we investigated the structure-activity relationship of nucleobase moieties using 2’-deoxy-carbocyclic guanosine as the lead compound, based on prior research. Subsequently, to efficiently identify lead compounds, we generated cells expressing HSV-TK, which phosphorylates a variety of nucleic acid analogs. These cells were then employed as an antiviral activity evaluation system against adenovirus. Unfortunately, no significant antiviral activity against adenovirus was observed for the nine synthesized compounds. However, laboratory evaluation of nucleic acid analogs using HSV-TK-positive cells has led to the discovery of a new hit compound.

Free Research Field

医薬品化学

Academic Significance and Societal Importance of the Research Achievements

本研究で新たに抗アデノウイルス活性を有するヒット化合物を見出すことができた。アデノウイルス感染症に有効な治療薬はないため、2'-デオキシ炭素環グアノシンを軸とした創薬研究を展開することで、抗アデノウイルス剤の開発につなげたい。また、本研究で作製した、核酸アナログのリン酸化代謝に着目したアッセイ系は、他ウイルス感染症治療薬の創製研究に応用が可能であると考えられる。本研究で得られた知見を基に、水平展開が期待される。