1,2,3-Triazole-Benzofused Molecular Conjugates as Potential Antiviral Agents against SARS-CoV-2 Virus Variants

Abstract

SARS-CoV-2 and its variants, especially the Omicron variant, remain a great threat to human health. The need to discover potent compounds that may control the SARS-CoV-2 virus pandemic and the emerged mutants is rising. A set of 1,2,3-triazole and/or 1,2,4-triazole was synthesized either from benzimidazole or isatin precursors. Molecular docking studies and in vitro enzyme activity revealed that most of the investigated compounds demonstrated promising binding scores against the SARS-CoV-2 and Omicron spike proteins, in comparison to the reference drugs. In particular, compound 9 has the highest scoring affinity against the SARS-CoV-2 and Omicron spike proteins in vitro with its IC50 reaching 75.98 nM against the Omicron spike protein and 74.51 nM against the SARS-CoV-2 spike protein. The possible interaction between the synthesized triazoles and the viral spike proteins was by the prevention of the viral entry into the host cells, which led to a reduction in viral reproduction and infection. A cytopathic inhibition assay in the human airway epithelial cell line (Vero E6) infected with SARS-CoV-2 revealed the effectiveness and safety of the synthesized compound (compound 9) (EC50 and CC50 reached 80.4 and 1028.28 µg/mL, respectively, with a selectivity index of 12.78). Moreover, the antiinflammatory effect of the tested compound may pave the way to reduce the reported SARS-CoV-2-induced hyperinflammation.

An Overview of 1,2,3-triazole-Containing Hybrids and Their Potential Anticholinesterase Activities

“…In addition to being structurally and chemically diverse, triazole-based molecules, as central scaffolds, are capable of interacting with a variety of receptors and enzymes, showing broad biological activities [ 19 , 20 ]. As a result, a wide range of triazole-containing compounds has been frequently employed as clinical drugs or candidates, and they are vital for treating a wide variety of diseases, including antibacterial [ 21 ], antifungal [ 22 ], antitubercular [ 23 ], antiviral [ 24 ], anti-Alzheimer’s [ 25 ], anticancer [ 26 ], antiparasitic [ 27 ], and antidiabetic treatments [ 28 ]. On the global market, triazole ring-containing drugs with medicinal value are actively exploited.…”

“…Recent studies on triazoles have utilized the principles of conjugate chemistry to assemble active pharmacophores to produce hybrid molecules with the desired activities. Triazoles clubbed with other pharmacophores have been found to have a broader spectrum with antimicrobial [ 52 ], anti-inflammatory [ 53 ], antineoplastic [ 26 ], antiobesity [ 54 ], antidiabetic [ 28 ], immunomodulatory [ 55 ], anticholinesterase [ 56 ], and antiviral activities [ 24 ]. In addition to the available triazole drugs, researchers are interested in exploring and developing new triazole-based scaffolds with major applications in biomedical and biotechnology fields.…”

Phenylpyrazolone-1,2,3-triazole Hybrids as Potent Antiviral Agents with Promising SARS-CoV-2 Main Protease Inhibition Potential

“…As a continuation of our interest in the click chemistry and biological properties of 1,2,3-triazoles [ 40 , 41 , 42 , 43 , 44 , 45 ], we have attempted to design and synthesize novel 1,2,3-triazoles linked to pyrazolone moiety for further investigation as lead compounds in medicinal chemistry. Thus, the general synthetic protocols adopted for the synthesis of the targeted 1,2,3-triazole-pyrazolone hybrids are represented in Scheme 1 , Scheme 2 and Scheme 3 .…”

Fungal Secondary Metabolites/Dicationic Pyridinium Iodide Combinations in Combat against Multi-Drug Resistant Microorganisms

“…The co-crystallized ligand LN1-255 was chosen as the comparison standard for the docking study in the experiment as a positive control (reference values). In the end, conformers that had the greatest binding scores and the best ligand–enzyme interactions were detected and examined [ 35 ].…”