Potential therapeutic effects of ester derivatives of Ribavirin against SARS-CoV-2

Ribavirin (1) esters 4–36 have been synthesized and tested for their anti-inflammatory and anti-viral properties against SARS-CoV-2. The impaired host immune response known as cytokine release syndrome is one of the major causes of COVID-19 infection-related death. The current study aimed to assess compounds 4–36 against viral infection in Vero cells (viral titration, cytopathic effects, anti-viral efficacy, and results of treatment points) and anti-inflammatory activity against cytokines (IL-2, GM-CSF, IL-6, TNF-α, IFN-γ and IL-1β) were quantified at the protein level by using ELISA, oxidative burst assay, nitric oxide inhibition assay, anti-proliferative activity. Cytotoxicity of compounds was also determined. Compound 13 showed promising results against anti-inflammatory activity (100.80%, IC₅₀ = 0.40 ± 0.01 µM) and SARS-CoV-2 infection inhibition up to 80% (IC₅₀ = 1.42 ± 0.28). Nonetheless, further investigation is necessary to enhance and synthesize long-acting Ribavirin esters-based anti-inflammatory and SARS-CoV-2 medications based on the identified patterns.