Developing Monotherapy against Hepatitis E Virus by Combining Phytochemicals Using Viro-Bioinformatics

Abstract

Hepatitis E virus (HEV) is a prominent cause of acute viral hepatitis worldwide, particularly threatening pregnant women and immunocompromised individuals due to the absence of specific antiviral treatments. This research employs an integrative in silico approach to identify phytochemical inhibitors against HEV, utilizing structure-based drug design and viroinformatics. Three essential HEV proteins—ORF1, ORF2, and ORF3—were selected for virtual screening. Phytochemicals from 15 medicinal plants were computationally screened, revealing seven promising candidates (Glycyrrhizin, Withanolides A, Rosmarinic acid, Zingerone, Chicoric acid, Acetogenins, Andrographolide) with strong binding affinities and favorable ADMET characteristics. Glycyrrhizin showed the highest binding affinity to the ORF2 capsid protein with a binding energy of −13.5 kcal/mol, indicating strong antiviral potential. To enhance phytochemical production, biosynthetic genes (4CL, SDR, RAS1, CYP88D6) were in silico cloned into plant expression vectors and computationally integrated into Ocimum sanctum and Glycyrrhiza glabra. KEGG pathway analysis confirmed increased metabolite synthesis and stress tolerance. This comprehensive computational pipeline supports the development of cost-effective, plant-based antivirals for HEV, paving the way for experimental validation and clinical application.