G-quadruplex-forming small RNA inhibits coronavirus and influenza A virus replication
Abstract Future pandemic threats may be caused by novel coronaviruses and influenza A viruses. Here we show that when directly added to a cell culture, 12mer guanine RNA (G12) and its phosphorothioate-linked derivatives (G12(S)), rapidly entered cytoplasm and suppressed the propagation of human coro...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07351-7 |
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| author | Ryoya Sekine Kouki Takeda Tsukasa Suenaga Satsuki Tsuno Takumi Kaiya Maki Kiso Seiya Yamayoshi Yoshihide Takaku Shiho Ohno Yoshiki Yamaguchi Seiichi Nishizawa Kazuhiro Sumitomo Kazufumi Ikuta Teru Kanda Yoshihiro Kawaoka Hidekazu Nishimura Shusuke Kuge |
| author_facet | Ryoya Sekine Kouki Takeda Tsukasa Suenaga Satsuki Tsuno Takumi Kaiya Maki Kiso Seiya Yamayoshi Yoshihide Takaku Shiho Ohno Yoshiki Yamaguchi Seiichi Nishizawa Kazuhiro Sumitomo Kazufumi Ikuta Teru Kanda Yoshihiro Kawaoka Hidekazu Nishimura Shusuke Kuge |
| author_sort | Ryoya Sekine |
| collection | DOAJ |
| description | Abstract Future pandemic threats may be caused by novel coronaviruses and influenza A viruses. Here we show that when directly added to a cell culture, 12mer guanine RNA (G12) and its phosphorothioate-linked derivatives (G12(S)), rapidly entered cytoplasm and suppressed the propagation of human coronaviruses and influenza A viruses to between 1/100 and nearly 1/1000 of normal virus infectivity without cellular toxicity and induction of innate immunity. Moreover, G12(S) alleviated the weight loss caused by coronavirus infection in mice. G12(S) might exhibit a stable G-tetrad with left-handed parallel-stranded G-quadruplex, and inhibit the replication process by impeding interaction between viral nucleoproteins and viral RNA in the cytoplasm. Unlike previous antiviral strategies that target the G-quadruplexes of the viral genome, we now show that excess exogenous G-quadruplex-forming small RNA displaces genomic RNA from ribonucleoprotein, effectively inhibiting viral replication. The approach has the potential to facilitate the creation of versatile middle-molecule antivirals featuring lipid nanoparticle-free delivery. |
| format | Article |
| id | doaj-art-e92c4b4a21f6422ea74f1fda45815993 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-e92c4b4a21f6422ea74f1fda458159932025-01-19T12:35:21ZengNature PortfolioCommunications Biology2399-36422025-01-018112110.1038/s42003-024-07351-7G-quadruplex-forming small RNA inhibits coronavirus and influenza A virus replicationRyoya Sekine0Kouki Takeda1Tsukasa Suenaga2Satsuki Tsuno3Takumi Kaiya4Maki Kiso5Seiya Yamayoshi6Yoshihide Takaku7Shiho Ohno8Yoshiki Yamaguchi9Seiichi Nishizawa10Kazuhiro Sumitomo11Kazufumi Ikuta12Teru Kanda13Yoshihiro Kawaoka14Hidekazu Nishimura15Shusuke Kuge16Division of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityDivision of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityDivision of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityDivision of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityDivision of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityDivision of Virology, Institute of Medical Sciences, The University of TokyoDivision of Virology, Institute of Medical Sciences, The University of TokyoDepartment of Chemistry, Graduate School of Science, Tohoku UniversityDivision of Structural Glycobiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityDivision of Structural Glycobiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityDepartment of Chemistry, Graduate School of Science, Tohoku UniversityDivision of Geriatric and Community Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical UniversityDivision of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical UniversityDivision of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical UniversityDivision of Virology, Institute of Medical Sciences, The University of TokyoVirus Research Center, Clinical Research Division, National Hospital Organization Sendai Medical CenterDivision of Microbiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityAbstract Future pandemic threats may be caused by novel coronaviruses and influenza A viruses. Here we show that when directly added to a cell culture, 12mer guanine RNA (G12) and its phosphorothioate-linked derivatives (G12(S)), rapidly entered cytoplasm and suppressed the propagation of human coronaviruses and influenza A viruses to between 1/100 and nearly 1/1000 of normal virus infectivity without cellular toxicity and induction of innate immunity. Moreover, G12(S) alleviated the weight loss caused by coronavirus infection in mice. G12(S) might exhibit a stable G-tetrad with left-handed parallel-stranded G-quadruplex, and inhibit the replication process by impeding interaction between viral nucleoproteins and viral RNA in the cytoplasm. Unlike previous antiviral strategies that target the G-quadruplexes of the viral genome, we now show that excess exogenous G-quadruplex-forming small RNA displaces genomic RNA from ribonucleoprotein, effectively inhibiting viral replication. The approach has the potential to facilitate the creation of versatile middle-molecule antivirals featuring lipid nanoparticle-free delivery.https://doi.org/10.1038/s42003-024-07351-7 |
| spellingShingle | Ryoya Sekine Kouki Takeda Tsukasa Suenaga Satsuki Tsuno Takumi Kaiya Maki Kiso Seiya Yamayoshi Yoshihide Takaku Shiho Ohno Yoshiki Yamaguchi Seiichi Nishizawa Kazuhiro Sumitomo Kazufumi Ikuta Teru Kanda Yoshihiro Kawaoka Hidekazu Nishimura Shusuke Kuge G-quadruplex-forming small RNA inhibits coronavirus and influenza A virus replication Communications Biology |
| title | G-quadruplex-forming small RNA inhibits coronavirus and influenza A virus replication |
| title_full | G-quadruplex-forming small RNA inhibits coronavirus and influenza A virus replication |
| title_fullStr | G-quadruplex-forming small RNA inhibits coronavirus and influenza A virus replication |
| title_full_unstemmed | G-quadruplex-forming small RNA inhibits coronavirus and influenza A virus replication |
| title_short | G-quadruplex-forming small RNA inhibits coronavirus and influenza A virus replication |
| title_sort | g quadruplex forming small rna inhibits coronavirus and influenza a virus replication |
| url | https://doi.org/10.1038/s42003-024-07351-7 |
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