A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant
Journal
EMBO molecular medicine
Journal Volume
14
Journal Issue
4
Date Issued
2022-04-07
Author(s)
Chang, Yi-Chung
Yang, Chi-Fan
Chen, Yi-Fen
Yang, Chia-Chun
Chou, Yuan-Lin
Chou, Hung-Wen
Chang, Tein-Yao
Hsu, Shu-Chen
Ieong, Si-Man
Tsai, Ya-Min
Liu, Ping-Cheng
Chin, Yuan-Fan
Fang, Jun-Tung
Kao, Han-Chieh
Lu, Hsuan-Ying
Chang, Jia-Yu
Weng, Ren-Shiuan
Tu, Qian-Wen
Chang, Fang-Yu
Huang, Kuo-Yen
Lee, Tong-Young
Abstract
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 IC50 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.
Subjects
COVID-19; K18-hACE2-transgenic mice; SARS-CoV-2; inhalation; siRNA
SDGs
Publisher
WILEY
Type
journal article