నైరూప్య

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.

Gulnara Abdrashidovna Yuldasheva*, Ilya Sergeevich Korotetskiy, Kaissar Tabynov, Kairat Tabynov, Aleksandr Ivanovich Ilin

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 was proposed by the molecular modeling method.

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 analysed. 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.

The 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. Result of experimental research and the proposed molecular model show that the nanocomplex of drug FS-1 have anticoronavirus effect.