tetano
Editor, Senior Moderator
Commun Biol
. 2025 Jan 15;8(1):27.
doi: 10.1038/s42003-024-07351-7. G-quadruplex-forming small RNA inhibits coronavirus and influenza A virus replication
Ryoya Sekine[SUP] #[/SUP][SUP] 1 [/SUP], Kouki Takeda[SUP] 1 [/SUP], Tsukasa Suenaga[SUP] 1 [/SUP], Satsuki Tsuno[SUP] 1 [/SUP], Takumi Kaiya[SUP] 1 [/SUP], Maki Kiso[SUP] 2 3 [/SUP], Seiya Yamayoshi[SUP] 2 3 4 [/SUP], Yoshihide Takaku[SUP] 5 [/SUP], Shiho Ohno[SUP] 6 [/SUP], Yoshiki Yamaguchi[SUP] 6 [/SUP], Seiichi Nishizawa[SUP] 5 [/SUP], Kazuhiro Sumitomo[SUP] 7 [/SUP], Kazufumi Ikuta[SUP] 8 [/SUP], Teru Kanda[SUP] 8 [/SUP], Yoshihiro Kawaoka[SUP] 2 3 4 [/SUP], Hidekazu Nishimura[SUP] 9 [/SUP], Shusuke Kuge[SUP] #[/SUP][SUP] 10 [/SUP]
Affiliations
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.
. 2025 Jan 15;8(1):27.
doi: 10.1038/s42003-024-07351-7. G-quadruplex-forming small RNA inhibits coronavirus and influenza A virus replication
Ryoya Sekine[SUP] #[/SUP][SUP] 1 [/SUP], Kouki Takeda[SUP] 1 [/SUP], Tsukasa Suenaga[SUP] 1 [/SUP], Satsuki Tsuno[SUP] 1 [/SUP], Takumi Kaiya[SUP] 1 [/SUP], Maki Kiso[SUP] 2 3 [/SUP], Seiya Yamayoshi[SUP] 2 3 4 [/SUP], Yoshihide Takaku[SUP] 5 [/SUP], Shiho Ohno[SUP] 6 [/SUP], Yoshiki Yamaguchi[SUP] 6 [/SUP], Seiichi Nishizawa[SUP] 5 [/SUP], Kazuhiro Sumitomo[SUP] 7 [/SUP], Kazufumi Ikuta[SUP] 8 [/SUP], Teru Kanda[SUP] 8 [/SUP], Yoshihiro Kawaoka[SUP] 2 3 4 [/SUP], Hidekazu Nishimura[SUP] 9 [/SUP], Shusuke Kuge[SUP] #[/SUP][SUP] 10 [/SUP]
Affiliations
- PMID: 39815031
- DOI: 10.1038/s42003-024-07351-7
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.