In only two years, the coronavirus disease 2019 (COVID-19) pandemic has had a devastating effect on public health all over the world and caused irreparable economic damage across all countries. Due to the limited therapeutic management of COVID-19 and the lack of tailor-made antiviral agents, finding new methods to combat this viral illness is now a priority. Herein, we report on a specific oligonucleotide-based RNA inhibitor targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It displayed remarkable spontaneous cellular uptake, >94% efficiency in reducing RNA-dependent RNA polymerase (RdRp) RNA levels in transfected lung cell lines, and >98% efficiency in reducing SARS-CoV-2 RNA levels in samples from patients hospitalized with COVID-19 following a single application.

The persistent coronavirus pandemic and the high mortality associated with COVID-19 demand urgent solutions. In this study, we reported the antiviral potential of a tailor-made oligonucleotide-based inhibitor targeting SARS-CoV-2, which is capable of spontaneously penetrating the cells, binding to viral RNA, and inducing its enzymatic degradation with a remarkable > 98% efficacy after a single application. The therapeutic potential of ASC1R demonstrated herein could translate into substantial clinical benefits for patients with COVID-19. Furthermore, in the context of infectious diseases, our results provide implications for the research and development of analogous antivirals for other diseases of viral origin. The findings could help to meet the global challenge of developing new and safe treatment modalities…

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