Journal
EMBO MOLECULAR MEDICINE
Volume 14, Issue 4, Pages -Publisher
WILEY
DOI: 10.15252/emmm.202115298
Keywords
COVID-19; inhalation; K18-hACE2-transgenic mice; SARS-CoV-2; siRNA
Categories
Funding
- Ministry of Science and Technology, Taiwan [MOST-110-2740-B-002-006, MOST109-2327-B-002-009, MOST 109-2124-M-002-012, MOST 109-0210-01-18-02, MOST 110-0210-01-22-02, 110-2314-B-002-282]
- Oneness Biotech Company
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The inhalable siRNA drug C6G25S, covering 99.8% of SARS-CoV-2 variants, shows effectiveness in inhibiting dominant strains and preventing lung damage in animal models.
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.
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