Cyclic lipopeptides as membrane fusion inhibitors against SARS-CoV-2: New tricks for old dogs.

With the resurgence of the coronavirus pandemic, the repositioning of FDA-approved drugs against coronovirus and finding alternative strategies for antiviral therapy are both important. We previously identified the viral lipid envelope as a potential target for the prevention and treatment of SARS-CoV-2 infection with plant alkaloids (Shekunov et al., 2021).

Synthesis of isomeric 4-(-methyltetrazolylamino)-2-phenyl-4-thiopyrano[2,3-]quinoline-3-carbaldehydes and 4-hydroxy-2-phenyl-4-thiopyrano[2,3-]quinoline-3-carbaldehyde based on tandem thiol-Michael and (aza)-Morita-Baylis-Hillman reactions and an study of the activity of the obtained compounds against influenza virus.

Unlabelled: 3-{[(1-Methyl-1-tetrazol-5-yl)imino]methyl}quinoline-2-thiol and 3-{[(2-methyl-2-tetrazol-5-yl)imino]methyl}quinoline-2-thiol were synthesized. The sequence of the thiol-Michael reaction and the (aza)-Morita-Baylis-Hillman reaction yielded 4-[(1-methyl-1-tetrazol-5-yl)amino]-2-phenyl-4-thiopyrano[2,3-]quinoline-3-carbaldehyde, 4-[(2-methyl-2-tetrazol-5-yl)amino]-2-phenyl-4-thiopyrano[2,3-]-quinoline-3-carbaldehyde, and 4-hydroxy-2-phenyl-4-thiopyrano[2,3-]quinoline-3-carbaldehyde. Cytotoxicity and antiviral activity against the A/Puerto Rico/8/34 (H1N1) influenza virus strain in MDCK cell culture were determined for the obtained compounds.

Plant Alkaloids Inhibit Membrane Fusion Mediated by Calcium and Fragments of MERS-CoV and SARS-CoV/SARS-CoV-2 Fusion Peptides.

To rationalize the antiviral actions of plant alkaloids, the ability of 20 compounds to inhibit calcium-mediated fusion of lipid vesicles composed of phosphatidylglycerol and cholesterol was investigated using the calcein release assay and dynamic light scattering. Piperine, tabersonine, hordenine, lupinine, quinine, and 3-isobutyl-1-methylxanthine demonstrated the most potent effects (inhibition index greater than 50%). The introduction of phosphatidylcholine into the phosphatidylglycerol/cholesterol mixture led to significant changes in quinine, hordenine, and 3-isobutyl-1-methylxanthine efficiency.

Synthesis, structure, and antiviral properties of novel 2-adamantyl-5-aryl-2-tetrazoles.

Unlabelled: The reaction of 5-aryl--tetrazoles with adamantan-1-ol in concentrated sulfuric acid proceeds regioselectively with the formation of the corresponding 2-adamantyl-5-aryl-2-tetrazoles. Nitration of these compounds leads to 2-(adamantan-1-yl)-5-(3-nitroaryl)-2tetrazoles. The structures and composition of the obtained novel 2-adamantyl-5-aryltetrazoles were proven by IR spectroscopy, H and C NMR spectroscopy, high-resolution mass spectrometry, and also by X-ray structural analysis.

Synthesis and antiviral activity of nonannulated tetrazolylpyrimidines.

Nonannulated tetrazolylpyrimidines in the structure of which the heterocyclic fragments are separated by hydrazinocarbonylmethyl, methylpyrazolyl groups or a sulfur atom were synthesized. Some of these compounds showed moderate activity against H1N1 subtype of influenza A virus. The selectivity index of the anti-influenza action of {5-[(4,6-dimethylpyrimidin-2-yl)sulfanyl]-1-tetrazol-1-yl}acetic acid, which has very low cytotoxicity, was twice as high as the selectivity index of the reference drug rimantadine.