Functional analysis of microRNAs in SARS-CoV-2 propagation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07039
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Osaka University
• Principal Investigator: Ono Chikako 大阪大学, 感染症総合教育研究拠点, 特任准教授(常勤) (30626437)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: SARS-CoV-2 / siRNA / 5’UTR

Outline of Final Research Achievements

In this study, we found that three siRNAs targeting SL1, SL2, SL3, and SL5 of the stem-loop (SL) structures in the 5'UTR of SARS-CoV-2 have an inhibitory effect on viral propagation. The inhibitory mechanism is suggested to be viral genome RNA degradation, and the inhibitory effect was observed against various epidemic strains of SARS-CoV-2 and SARS-CoV. In addition, the inhibitory effect was also observed when treated with siRNA at post-infection. On the other hand, during serial passages of SARS-CoV-2 in the presence of each siRNA, resistant mutants were obtained, respectively, but all of them had reduced virus production efficiency, and the introduced mutations were detected in small amounts in the public database but were not maintained, suggesting that they are not advantageous mutations for viral propagation.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた3つのsiRNAは、標的部位がSARS-CoV-2のみならずSARS-CoVを含めたサルベコウイルス属でも保存されており、いずれに対しても抑制効果が認められたため、今後出現しうるサルベコウイルス属から派生した新興・再興ウイルスに対しても有効であることが期待される。またこのようなウイルス増殖にとって重要な保存性の高い領域を標的とすることは、有効なウイルス治療戦略となると考えられる。
またウイルス感染後にsiRNAを導入しても抑制効果が認められたことから、ウイルスゲノムを直接標的とする新規SARS-CoV-2治療法の開発につながると期待される。