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

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.

Antiviral activity of benzydamine hydrochloride against SARS-CoV-2 in vitro model

Due to the emergence of a new coronavirus infection COVID-19, scientists around the world are actively working on a vaccine against the SARS-CoV-2 coronavirus. At the same time, it is possible that existing medications can help in the fight against this disease. The local antiseptic drug benzidamine hydrochloride in the early stages of illness can prevent the virus from entering the lower respiratory tract and potentially reduce the severe illness associated with pneumonia and, as a result, reduce COVID-19-related hospitalizations, which can significantly reduce the burden on the health care system. The aim: to evaluate the antiviral activity of benzidamine hydrochloride against SARS-CoV-2 in vitro. Material and methods. Antiviral properties of benzidamine hydrochloride were studied in vitro in non-toxic concentrations on monolayer of Vero-E6 cells infected with pandemic strain of SARS-CoV-2 coronavirus in treatment and prophylactic scheme of the compound and virus administration. Results. Benzidamine hydrochloride has antiviral activity (15,0 mcg/ml), the efficiency of its antiviral action is directly proportional to the concentration of the substance. Conclusions. Taking into account very limited range of antiviral drugs with direct action on SARS-CoV-2 virus, the studied preparation can be used in complex therapy at early stages of the disease, which can prevent virus penetration into lower respiratory tract and potentially reduce the number of complications. © 2021, Numikom. All rights reserved.