Plant halides as potential norovirus 3CLpro inhibitors: An in silico approach

Abstract

Norovirus, a member of Caliciviridae causes severe gastroenteritis in all phases of human life. Norovirus is a major global cause of acute gastroenteritis with high mortality in children and immunocompromised individuals. The norovirus 3CL protease (3CLpro) is a cysteine protease that post-translationally cleaves ORF1 (open reading frame 1)-encoded polyproteins into six non-structural proteins (nsPs). These nsPs p48, NTPase, p22, VPg, Pro, and Pol are essential for the replication and transcription of the viral genome hence 3CLpro is inevitable for norovirus multiplication. The indispensable role multiplication and conserved nature of 3CLpro makes it an attractive target for anti-norovirus therapeutics. Currently there is no approved drug or vaccine against norovirus. In the current investigation, an in silico approach has been employed to find lead halide secondary metabolite from higher plants against 3CLpro. The library of 66 halide plant metabolites from terrestrial habitats has been screened for drug likeliness and ADME qualified 36 molecules were subjected to molecular docking. The molecule, gravacridonechlorine in complex with 3CLpro exhibited the highest binding affinity (-6.9 kcal/mol) and validated through MD simulation and MMPBSA (ΔG_bind -134.142 kJ/mol). The findings concluded that the gravacridonechlorine-3CLpro complex is favoured energetically and can be a suitable inhibitor for norovirus.