Role of Pin1 in the proliferation of SARS-CoV-2

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19380
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Hiroshima University
• Principal Investigator: ASANO TOMOICHIRO 広島大学, 医系科学研究科(医), 教授 (70242063)
• Co-Investigator(Kenkyū-buntansha): 中津 祐介 広島大学, 医系科学研究科(医), 准教授 (20452584) ; 山本屋 武 広島大学, 医系科学研究科(医), 助教 (50760013)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: Pin1 / SARS-CoV-2 / COVID-19

Outline of Final Research Achievements

Pin1 is involved in the pathogenesis of many diseases including cancers and metabolic syndrome. Furthermore, Pin1 is required to grow human immunodeficiency virus, hepatitis B virus, and other viruses. In this project, it was demonstrated that applying Pin1 knockdown or Pin1 inhibitors inhibited SARS-CoV-2 growth. Indeed, Pin1 was reported to bind to phosphorylated Ser79 in the Ser79-Pro sequence of the N protein. In addition, viral transcription of SARS-CoV-2 is inhibited by the use of Pin1 inhibitors, suggesting RNA synthesis of SARS-CoV-2 to likely be promoted by Pin1. The N protein has a sequence that is highly conserved among coronaviruses, but this Ser79-Pro sequence is not found in closely related viruses such as SARS-CoV and MERS-CoV and is specific to SARS-CoV-2. The Ser-Pro site of this N protein might be one of the causes of SARS-CoV2 exacerbation and spread of the infection.

Free Research Field

病態生化学

Academic Significance and Societal Importance of the Research Achievements

新型コロナウイルスSARS-CoV-2によるパンデミックが起こり、多くの方が亡くなるなど多大な損失が生じ、私たちの生活も大きく変わってしまった。この感染症COVID-19を制御するための抗ウイルス剤は、まだ種類が限られており、新たな薬剤の開発が急務である。我々は、Pin1 siRNAによるPin1の阻害、あるいはPin1阻害薬の添加によって、培養細胞でのSARS-CoV-2の増殖を阻害することを見出した。我々が研究開発したPin1阻害薬は、他のCOVID-19治療薬とは異なる作用点をもつ薬剤であり、このようにPin1阻害薬をCOVID-19に対して使用することは新規の試みである。