Open AccessA siRNA targets and inhibits a broad range of SARS‐CoV‐2 infections including Delta variant
Author(s) -
Chang YiChung,
Yang ChiFan,
Chen YiFen,
Yang ChiaChun,
Chou YuanLin,
Chou HungWen,
Chang TeinYao,
Chao TaiLing,
Hsu ShuChen,
Ieong SiMan,
Tsai YaMin,
Liu PingCheng,
Chin YuanFan,
Fang JunTung,
Kao HanChieh,
Lu HsuanYing,
Chang JiaYu,
Weng RenShiuan,
Tu QianWen,
Chang FangYu,
Huang KuoYen,
Lee TongYoung,
Chang SuiYuan,
Yang PanChyr
Publication year - 2022
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202115298
Subject(s) - china , library science , visualization , political science , computer science , artificial intelligence , law
The emergence of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) variants has altered the trajectory of the COVID‐19 pandemic and raised some uncertainty on the long‐term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS‐CoV‐2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS‐CoV‐2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC 50 in vitro . Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18‐hACE2‐transgenic mice, accompanied by a significant prevention of virus‐associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID‐19 pandemic.