Dear Editor, Since the declaration of COVID-19 as a global pandemic on March 11, 2020, this pandemic has been circulating for 17 months throughout the world, leading to more than 200 million infections and nearly 4.4 million deaths as of August 15, 2021. The pathogen of COVID-19 is a novel coronavirus named SARS-CoV-2, which shares~ 79% genome sequence identity with SARS-CoV. 1 At the early stage of the COVID-19 outbreak, SARS-CoV-2 caused great panic in the hardest-hit areas due to its high transmissibility and pathogenicity. To fight the COVID-19 crisis, drug repurposing was immediately pursued in order to find potential therapeutics. Until now, though some treatment options are available, there still lack effective antiviral agents. Vaccination is considered as the best way to control this global pandemic, but the emerging SARS-CoV-2 variants pose a great challenge to the protective efficacy of the existing vaccines. Hence, in the long run, finding an effective antiviral medication against the SARS-CoV-2 infection is a pressing need.

Great efforts have been put into the development of novel drugs against SARS-CoV-2 infection. Currently, remdesivir (RDV)(Fig. 1 a), an intravenously administered nucleotide prodrug, is the only approved anti-SARS-CoV-2 drug. However, it displays limited therapeutic efficacy especially for severe COVID-19 cases. 2 Nucleoside analogs are an important class of antivirals acting by interfering with the viral polymerases that are highly conserved in the active center. Besides RDV, two oral nucleoside analogs, molnupiravir (EIDD-2801) 3 and AT-527, 4 have entered phase II/III clinical studies. Herein, we reported the discovery of an oral anti-SARS-CoV-2 nucleoside candidate, VV116, which displays favorable drug-like properties, and is going to be evaluated in clinical study for treating COVID-19.