Synthesis of 1,3,5-Triazine-Indole Conjugates as Broad-Spectrum Coronavirus Entry Inhibitors
Shazia Asghar1, Leentje Persoons2, Yanicka Smolders2
1Department of Chemistry, Quaid-I-Azam University, Islamabad, Pakistan.
Abstract:
A series of hybrid molecules containing indole and 1,3,5-triazine scaffolds was synthesized and evaluated for their antiviral activity against several human RNA and DNA viruses. The conjugates displayed overall low cytotoxicity (CC50 > 50 µM) and potent antiviral activity across a coronavirus panel, with the most promising analogs (compounds 5d, 5g and 5o) showing sub- to low-micromolar EC50 values against HCoV-OC43, HCoV-229E, and SARS-CoV-2. Structure-activity relationship studies highlighted that the substitution pattern on the anilino moiety allowed to modulate antiviral activity. Time-of-drug addition, adsorption, and fusion assays indicated inhibition of viral replication at an early viral entry step, consistent with inhibition of spike-mediated membrane fusion. Overall, these data suggest that 1,3,5-triazine-indole conjugates are a promising scaffold to develop broad-spectrum coronavirus entry inhibitors. ADMET profiling of lead compounds (5d, 5g, and 5o) revealed favorable pharmacokinetic properties, including high oral absorption, limited CNS penetration, and non-mutagenic safety profiles.
More Related Videos
06:34Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)
Published on: June 20, 2014
10:29Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Related Concept Videos
Inhibitors of Viral Protein Synthesis
Inhibitors Of Virion Release
Inhibitors of Bacterial DNA Synthesis
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Inhibitors of Virion Maturation and Assembly
Inhibitors of Bacterial Protein Synthesis
