Yi-Chung Chang, Chi-Fan Yang, Yi-Fen Chen, Chia-Chun Yang, Yuan-Lin Chou, Hung-Wen Chou, Tein-Yao Chang, Tai-Ling Chao, Shu-Chen Hsu, Si-Man Ieong, Ya-Min Tsai, Ping-Cheng Liu, Yuan-Fan Chin, Jun-Tung Fang, Han-Chieh Kao, Hsuan-Ying Lu, Jia-Yu Chang, Ren-Shiuan Weng, Qian-Wen Tu, Fang-Yu Chang, Kuo-Yen Huang, Tong-Young Lee, Sui-Yuan Chang, Pan-Chyr Yang

EMBO Mol Med. 2022 Feb 8;e15298.

https://pubmed.ncbi.nlm.nih.gov/35138028/

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.

Keywords: COVID-19; K18-hACE2-transgenic mice; SARS-CoV-2; inhalation; siRNA.