2023 Fiscal Year Final Research Report
Development of a novel therapeutic agent against COVID-19 by targeting newly synthesized spike protein in cells
| Project/Area Number |
21K19344
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 47:Pharmaceutical sciences and related fields
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| Research Institution | Doshisha University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
和久 剛 同志社大学, 生命医科学部, 准教授 (40613584)
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| Project Period (FY) |
2021-07-09 – 2024-03-31
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| Keywords | COVID-19 / Sタンパク / ペプチドライブラリー / スクリーニング / 多価型ペプチド |
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| Outline of Final Research Achievements |
The main purpose of this study is to develop a novel therapeutic agent against SARS-CoV-2 by targeting the receptor binding region (RBD) of the spike protein (S-protein). Since S-protein functions by forming a trimeric structure, here we developed a novel technique, in which a series of tetravalent peptides with high-affinity binding capacity to RBD was identified by screening a cellulose sheet with hundreds of tetravalent peptide-libraries synthesized on it. We identified 10 tetravalent peptides with high affinity binding to RBD. Three of them inhibited the binding of RBD with its receptor ACE2 with thouthands fold potency compared to a peptide derived from ACE2 that has been shown to inhibit the binding, indicating that these peptides can be a novel type of therapeutic agent against COVID-19.
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| Free Research Field |
生化学
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| Academic Significance and Societal Importance of the Research Achievements |
COVID-19はSARS-CoV-2を原因ウイルスとする感染症である。すでにワクチン開発が強力に進められその有効性が認められているが、その一方で未だに有効性な治療薬は存在しない。本研究で取得した４価型RBD阻害ペプチドは、RBDとその受容体であるACE2との結合を極めて強力に阻害することが示されたことから、新たなCOVID-19治療薬として期待できる。これまでの技術では、RBDとACE2との３量体同士の極めて強い結合を阻害する分子の同定は極めて困難であった。本研究で取得した分子は、新たに開発した手法を用いて既知の配列に依存することなく同定したものであり、この点高い優位性を持つ。
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