[Antiviral properties of synthetic histidine derivatives containing membranotropic volumetrical carbocycles in their molecule against SARS-CoV-2 virus in vitro ].

Autor:	Garaev TM; National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya., Grebennikova TV; National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya., Avdeeva VV; Kurnakov Institute of General and Inorganic Chemistry of Russian Academy of Sciences., Lebedeva VV; National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya., Larichev VF; National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya.
Jazyk:	ruština
Zdroj:	Voprosy virusologii [Vopr Virusol] 2023 Mar 11; Vol. 68 (1), pp. 18-25. Date of Electronic Publication: 2023 Mar 11.
DOI:	10.36233/0507-4088-147
Abstrakt:	Introduction: Currently, low molecular-weight compounds are being developed as potential inhibitors of CoVs replication, targeting various stages of the replication cycle, such as major protease inhibitors and nucleoside analogs. Viroporins can be alternative protein targets. The aim of this study is to identify antiviral properties of histidine derivatives with cage substituents in relation to pandemic strain SARS-CoV-2 in vitro. Materials and Methods: Combination of histidine with aminoadamantane and boron cluster anion [B10H10]2 (compounds IIV) was carried out by classical peptide synthesis. Compound were identified by modern physicochemical methods. Antiviral properties were studied in vitro on a monolayer of Vero E6 cells infected with SARS-CoV-2 (alpha strain) with simultaneous administration of compounds and virus. Results: Derivatives of amino acid histidine with carbocycles and boron cluster were synthesized and their antiviral activity against SARS-CoV-2 was studied in vitro. Histidine derivatives with carbocycles and [B10H10]2 have the ability to suppress virus replication. The solubility of substances in aqueous media can be increased due to formation of hydrochloride or sodium salt. Discussion: 2HCl*H-His-Rim (I) showed some effect of suppressing replication of SARS-CoV-2 at a viral load of 100 doses and concentration 31.2 g/ml. This is explained by the weakly basic properties of compound I. Conclusion: The presented synthetic compounds showed moderate antiviral activity against SARS-CoV-2. The obtained compounds can be used as model structures for creating new direct-acting drugs against modern strains of coronaviruses.
Databáze:	MEDLINE
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