Halogen-guided kottamide d derivatives as potent inhibitors of influenza a h1n1 (pa endonuclease) and h5n1 (neuraminidase)

Abstract

The present invention is a Halogen-Guided Kottamide D Derivatives in which Kottamide D used as the core scaffold. Fluorinated (KD-1) and chlorinated (KD-2) analogues are produced via halogen replacements at the C-5 and C-6 locations of the indole ring. Due to their functions in viral transcription and egress, the H5N1 neuraminidase and H1N1 PA endonuclease are targeted. Due to their superior bioavailability and compliance with drug-likeness criteria, KD-1 and KD-2 are found to be viable candidates. According to docking tests, KD-1 exhibited a strong affinity for H5N1, whereas KD-2 had the best binding energy for H1N1. Their potential as dual-mechanism antiviral options against influenza A is supported by quantum investigations that revealed optimum electrical characteristics and demonstrated efficient halogenation.

Images