[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.

New type of RNA virus replication inhibitor based on decahydro-closo-decaborate anion containing amino acid ester pendant group.

In this work, a synthetic approach to prepare an example of new class of the derivatives of the closo-decaborate anion with amino acids detached from the boron cluster by pendant group has been proposed and implemented. Compound Na2[B10H9-O(CH2)4C(O)-His-OMe] was isolated and characterized. This compound has an inorganic hydrophobic core which is the 10-vertex boron cage and the -O(CH2)4C(O)-His-OMe organic substituent. It has been shown to possess strong antiviral activity in vitro against modern strains of A/H1N1 virus at 10 and 5 µg/mL. The compound has been found to be non-cytotoxic up to 160 µg/mL. At the same time, the compound has been found to be inactive against SARS-CoV-2, indicating specific activity against RNA virus replication. Molecular docking of the target derivative of the closo-decaborate anion with a model of the transmembrane region of the M2 protein has been performed and the mechanism of its antiviral action is discussed.

Performance of electrochemical immunoassays for clinical diagnostics of SARS-CoV-2 based on selective nucleocapsid N protein detection: Boron-doped diamond, gold and glassy carbon evaluation.

The 21st century has already brought us a plethora of new threats related to viruses that emerge in humans after zoonotic transmission or drastically change their geographic distribution or prevalence. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first spotted at the end of 2019 to rapidly spread in southwest Asia and later cause a global pandemic, which paralyzes the world since then. We have designed novel immunosensors targeting conserved protein sequences of the N protein of SARS-CoV-2 based on lab-produced and purified anti-SARS-CoV-2 nucleocapsid antibodies that are densely grafted onto various surfaces (diamond/gold/glassy carbon). Titration of antibodies shows very strong reactions up to 1:72 900 dilution. Next, we showed the mechanism of interactions of our immunoassay with nucleocapsid N protein revealing molecular recognition by impedimetric measurements supported by hybrid modeling results with both density functional theory and molecular dynamics methods. Biosensors allowed for a fast (in less than 10 min) detection of SARS-CoV-2 virus with a limit of detection from 0.227 ng/ml through 0.334 ng/ml to 0.362 ng/ml for glassy carbon, boron-doped diamond, and gold surfaces, respectively. For all tested surfaces, we obtained a wide linear range of concentrations from 4.4 ng/ml to 4.4 pg/ml. Furthermore, our sensor leads to a highly specific response to SARS-CoV-2 clinical samples versus other upper respiratory tract viruses such as influenza, respiratory syncytial virus, or Epstein-Barr virus. All clinical samples were tested simultaneously on biosensors and real-time polymerase chain reactions.

First electrochemical evaluation of favipiravir used as an antiviral option in the treatment of COVID-19: A study of its enhanced voltammetric determination in cationic surfactant media using a boron-doped diamond electrode.

Favipiravir, a promising antiviral agent, is undergoing clinical trials for the potential treatment of the novel coronavirus disease 2019 (COVID-19). This is the first report for the electrochemical activity of favipiravir and its electroanalytical sensing. For this purpose, the effect of cationic surfactant, CTAB was demonstrated on the enhanced accumulation of favipiravir at the surface of cathodically pretreated boron-doped diamond (CPT-BDD) electrode. At first, the electrochemical properties of favipiravir were investigated in the surfactant-free solutions by the means of cyclic voltammetry. The compound presented a single oxidation step which is irreversible and adsorption controlled. A systematic study of various operational conditions, such as electrode pretreatment, pH of the supporting electrolyte, concentration of CTAB, accumulation variables, and instrumental parameters on the adsorptive stripping response, was examined using square-wave voltammetry. An oxidation signal at around +1.21 V in Britton-Robinson buffer at pH 8.0 containing 6 × 10-4 M CTAB allowed to the adsorptive stripping voltammetric determination of favipiravir (after 60 s accumulation step at open-circuit condition). The process could be used in the concentration range with two linear segments of 0.01-0.1 µg mL-1 (6.4 × 10-8-6.4 × 10-7 M) and 0.1-20.0 µg mL-1 (6.4 × 10-7-1.3 × 10-4 M). The limit of detection values were found to be 0.0028 µg mL-1 (1.8 × 10-8 M), and 0.023 µg mL-1 (1.5 × 10-7 M) for the first and second segments of calibration graph, respectively. The feasibility of developed methodology was tested to the analysis of the commercial tablet formulations and model human urine samples.

Could boron-containing compounds (BCCs) be effective against SARS-CoV-2 as anti-viral agent?

BACKGROUND: Seven dioxaborole compounds are investigated in this study. Structural and spectral characterizations are done at the M062X/6-31+G(d,p) level in water. Active sites of these compounds are determined by contour plots of frontier molecular orbital and molecular electrostatic potential (MEP) maps. Electrophilic and nucleophilic attack regions are determined. Since SARS-CoV-2 is a worldwide health problem, antiviral properties of studied boron-containing compounds are investigated by molecular docking calculations. In addition to these calculations, MM/PSBA calculations are performed. RESULTS AND CONCLUSION: It is found that the studied boron compounds can be good drug candidates against the main protease of SARS-CoV-2, while the best of them is 4,6-di-tert-butyl-2-(4-methoxyphenyl)benzo[d][1,3,2] dioxaborole (B2) (Tab. 3, Fig. 8, Ref. 23).