Molecular Model of Inhibition of the Catalytic Fragment of Domain ExoN of Exoribonuclease of Virus SARS-CoV-2-betacoronavirus B by Drug FS-1 Containing Molecular Iodine and Lithium and Magnesium Halides.

Abstract

Abstract Background: The 2020 pandemic has clearly shown the relevance of creating antiviral drugs. One of the targets of the drug is the active center of the vital enzymes of the virus. Such drugs include the antibacterial. and antiviral drug FS-1. Method: For the study, a coronavirus cell culture line was used. The VERO C1008 cell culture [Vero 76, clone E6, Vero E6] (ATCC® CRL1586™) was adapted for use in the COVID-19 model. Antiviral activity of TI investigates in vitro by therapeutic, prophylactic and virus inhibition scheme. Structures modeling the mechanism anticoronavirus effect of drug FS-1 are calculated using the approach DFT/B3PW91/6-31G**. Total energies of the complexes in aqueous solution calculated using model COSMO. Result: Drug FS-1 substance has virus inhibitory activity at a concentration of 3.36 mg/ml in Vero E6 cell culture against coronavirus infection COVID-19 (strain hCoV19/Kazakhstan/KazNAU-NSCEDI-481/2020) in a dose of 100 TCID50/0.2 ml. For the genome of the virus taken from isolate of SARS-CoV-2/INMI1/human/2020/ITA, the frequency of occurrence of nucleotide triplets has been analyzed. The most common triplet is AAA (281). Using the DFT/B3PW91/6-31G** approach, it is shown the active complexes of drug FS-1: [MgI3LiII2]+ and Li(Cl)I3, can segregate from the dextrin helix and can form a complex with donor-active atoms of the triplet AAA of viral RNA. Complexes of active center of nanocomplex FS-1 with triplet AAA destroy the complex formed by a phosphate group of viral RNA and a catalytic fragment of domain ExoN of exoribonuclease, and form a new nucleoprotein complex where lithium chloride and [MgI3LiII2]+ bind both viral RNA and magnesium ions of the catalytic fragment of domain ExoN of exoribonuclease. The conditions of cleavage of RNA are violated. Conclusion Results of experimental research and the proposed molecular model show that the nanocomplex of drug FS-1 have anticoronavirus effect.