Evaluation of the Antiviral Potential of Modified Heterocyclic Base and 5’-Norcarbocyclic Nucleoside Analogs Against SARS-CoV-2

Abstract

The pandemic caused by the novel betacoronavirus SARS-CoV-2 has already claimed more than3.5 million lives. Despite the development and use of anti-COVID-19 vaccines, the disease remains a majorpublic health challenge throughout the world. Large-scale screening of the drugs already approved for thetreatment of other viral, bacterial, and parasitic infections, as well as autoimmune, oncological, and otherdiseases is currently underway as part of their repurposing for development of effective therapeutic agentsagainst SARS-CoV-2. In this work, we present the results of a phenotypic screening of libraries of modifiedheterocyclic bases and 5’-norcarbocyclic nucleoside analogs previously synthesized by us. We identified twoleading compounds with apparent potential to inhibit SARS-CoV-2 replication and EC50 values in a range of20–70 μM. The structures of these compounds can be further optimized to develop an antiviral drug.