Influenza viruses, which have the ability to mutate rapidly and cause outbreaks worldwide, remain poorly controlled. Today the development of new organofluorine compounds is one of the current areas of medical chemistry. The aim of our work is to determine the antiviral activity of 2-(2,4-dioxopyrimidin-1-yl)-5-hydroxymethyl-5-(trifluoromethyl)tetrahydrothiophene (10S-46) against influenza virus in vitro, to define the probable target of its action with a further increase in affinity for the target by methods in silico.

In vitro studies were performed on MDCK culture, cytotoxicity was determined by the MTT assay. Antiviral activity (influenza A virus type H1N1) was determined by a post-exposure scheme with detection of the CPE using gentian violet. The 10S-46 target was searched using the simulation of molecular dynamics and molecular docking. An iterative approach was used to increase the affinity of the test compound for a pre-identified target.

The cytotoxic concentration (CC50) of the test compound was 530 μg/ml. Antiviral activity against H1N1 was recorded in the range of 60 – 70% at concentrations from 50 to 0.5 μg/ml. The probable target for 10S-46 was the Cap-binding domain of H1N1 RdRp. The obtained derivatives 10S-46-m2, 10S-46-m16 and 10S-46-m18 in complex with the target protein showed greater stability compared to the 10S-46.

The presence of anti-influenza effect of the 10S-46 was established, a possible target of its action was identified, and three potentially more active compounds were developed, which indicates the prospects of their further study in vitro.