tetano
Editor, Senior Moderator
EMBO Mol Med
. 2022 Feb 8;e15298.
doi: 10.15252/emmm.202115298. Online ahead of print.
A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant
Yi-Chung Chang[SUP] 1 [/SUP], Chi-Fan Yang[SUP] 2 [/SUP], Yi-Fen Chen[SUP] 1 [/SUP], Chia-Chun Yang[SUP] 2 [/SUP], Yuan-Lin Chou[SUP] 2 [/SUP], Hung-Wen Chou[SUP] 1 [/SUP], Tein-Yao Chang[SUP] 3 [/SUP], Tai-Ling Chao[SUP] 4 [/SUP], Shu-Chen Hsu[SUP] 3 [/SUP], Si-Man Ieong[SUP] 4 [/SUP], Ya-Min Tsai[SUP] 4 [/SUP], Ping-Cheng Liu[SUP] 3 [/SUP], Yuan-Fan Chin[SUP] 3 [/SUP], Jun-Tung Fang[SUP] 4 [/SUP], Han-Chieh Kao[SUP] 4 [/SUP], Hsuan-Ying Lu[SUP] 3 [/SUP], Jia-Yu Chang[SUP] 3 [/SUP], Ren-Shiuan Weng[SUP] 1 [/SUP], Qian-Wen Tu[SUP] 1 [/SUP], Fang-Yu Chang[SUP] 1 [/SUP], Kuo-Yen Huang[SUP] 5 [/SUP], Tong-Young Lee[SUP] 2 [/SUP], Sui-Yuan Chang[SUP] 4 6 [/SUP], Pan-Chyr Yang[SUP] 7 8 9 [/SUP]
Affiliations
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 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[SUB]50[/SUB] in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by co-treatment in K18-hACE2-transgenic mice, accompanying with a significant prevention of virus-associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggests that C6G25S provides an alternative and effective approach to combating the COVID-19 pandemic.
Keywords: COVID-19; Inhalation; K18-hACE2-transgenic mice; SARS-CoV-2; siRNA.
. 2022 Feb 8;e15298.
doi: 10.15252/emmm.202115298. Online ahead of print.
A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant
Yi-Chung Chang[SUP] 1 [/SUP], Chi-Fan Yang[SUP] 2 [/SUP], Yi-Fen Chen[SUP] 1 [/SUP], Chia-Chun Yang[SUP] 2 [/SUP], Yuan-Lin Chou[SUP] 2 [/SUP], Hung-Wen Chou[SUP] 1 [/SUP], Tein-Yao Chang[SUP] 3 [/SUP], Tai-Ling Chao[SUP] 4 [/SUP], Shu-Chen Hsu[SUP] 3 [/SUP], Si-Man Ieong[SUP] 4 [/SUP], Ya-Min Tsai[SUP] 4 [/SUP], Ping-Cheng Liu[SUP] 3 [/SUP], Yuan-Fan Chin[SUP] 3 [/SUP], Jun-Tung Fang[SUP] 4 [/SUP], Han-Chieh Kao[SUP] 4 [/SUP], Hsuan-Ying Lu[SUP] 3 [/SUP], Jia-Yu Chang[SUP] 3 [/SUP], Ren-Shiuan Weng[SUP] 1 [/SUP], Qian-Wen Tu[SUP] 1 [/SUP], Fang-Yu Chang[SUP] 1 [/SUP], Kuo-Yen Huang[SUP] 5 [/SUP], Tong-Young Lee[SUP] 2 [/SUP], Sui-Yuan Chang[SUP] 4 6 [/SUP], Pan-Chyr Yang[SUP] 7 8 9 [/SUP]
Affiliations
- PMID: 35138028
- DOI: 10.15252/emmm.202115298
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 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[SUB]50[/SUB] in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by co-treatment in K18-hACE2-transgenic mice, accompanying with a significant prevention of virus-associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggests that C6G25S provides an alternative and effective approach to combating the COVID-19 pandemic.
Keywords: COVID-19; Inhalation; K18-hACE2-transgenic mice; SARS-CoV-2; siRNA.