Development of a degrader for SARS-CoV-2 3CL protease

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22723
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Konno Sho 東京薬科大学, 薬学部, 助教 (70882190)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 3CLプロテアーゼ / SARS-CoV-2 / プロテアーゼ阻害剤 / プロテインノックダウン / COVID-19 / PROTAC

Outline of Final Research Achievements

The novel coronavirus, SARS-CoV-2, has been identified as the causative agent for the current coronavirus disease (COVID-19) pandemic. 3CL protease plays a pivotal role in the processing of viral polyproteins. Herein, we developed 3CL protease degraders based on our original 3CL protease inhibitor YH-53. We demonstrated that most of synthesized 3CL protease degraders showed comparable inhibitory activities of SARS-CoV-2 3CL protease with YH-53, which suggests that these molecules have a potential to induce the degradation of 3CL protease. This study would offer a new therapeutic strategy for a development of antiviral agents.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

COVID-19は人類共通の災禍であり、治療薬開発は急務である。一方、新薬開発は膨大な資金と時間、人的資源を必要とすることから、新たな創薬アプローチの提案および確立は喫緊の課題である。本研究では、タンパク質分解誘導と呼ばれる技術をCOVID-19治療に応用可能か検証しており、SARS-CoV-2を含めたウイルス感染症に対する新しい治療戦略となる可能性を秘めている。