Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening

Abstract

Hepatitis E virus (HEV) is the notable causative agent of acute and chronic hepatic, renal, pancreatic, neurological, and hematopoietic blood cell infections with high risk in immunocompromised patients. Hepatic failure is mostly documented among adults, pregnant women, and patients with preexisting liver disease. HEV is a positive sense RNA virus of 7.2 kb genome size with typically three open reading frames (ORFs) which play essential roles in viral replication, genome assembly, and transcription. The mutational substitution in the viral RNA genome makes more it difficult to understand the actual relationship in the host–virus association. ORFs of HEV encode different structural and non-structural proteins and one of them is the capsid protein which is coded by ORF2. The capsid protein mediates the encapsulation of the viral genome as well as being involved in virion assembly. In the current study, the ligand-based docking approach was employed to inhibit the active amino acids of the viral capsid protein. Depending upon S-score, ADMET profiling, and drug scanning, the top ten tetrapeptides were selected as potential drug candidates with no toxicity counter to HEV receptor protein. The S-score or docking score is a mathematical function which predicts the binding affinities of docked complexes. The binding affinity of the predicted drug–target complexes helps in the selectivity of the desired compound as a potential drug. The best two selected peptides (i.e., TDGH with S-score of −8.5 and EGDE with S-score of −8.0) interacted with the active site amino acids of the capsid protein (i.e., Arg399, Gln420, and Asp444). The molecular dynamics simulations of RMSD trajectories of TDGH–capsid protein and EDGE–capsid protein have revealed that both docked complexes were structurally stable. The study revealed that these tetrapeptides would serve as strong potential inhibitors and a starting point for the development of new drug molecules against the HEV capsid protein. In future, in vivo studies are needed to explore selected peptides as potential drug candidates.

Network Pharmacology and Experimental Validation to Explore the Potential Mechanism of Nigella sativa for the Treatment of Breast Cancer

“…In this study, molecular docking was performed for phytocompounds sourced from N. sativa against five target proteins (i.e., EGFR, MAPK1, MAPK3, PTGS2, and ESR1), with the objective of investigating their potential for treating or suppressing breast cancer. PyRx software (v0.8) was used for molecular docking analysis to reveal the binding modes of ligand-protein interactions [13,53]. This approach complements the findings of NP and confirms the phytochemicals as lead compounds.…”

“…The compounds analyzed violated only one of the five Ro5 rules (Table 3). According to previous research [13], a compound can be considered as a potential drug candidate if it violates one rule (out of five). To further evaluate the pharmacological potential of the selected phytochemicals from a medical perspective, the admetSAR tool was used.…”

Research progress on natural products against hepatocellular carcinoma

“…Natural products are widely used in the treatment process before and after surgery, helping to reduce surgical risk, reduce postoperative complications [169], and promote tissue repair [40]. In addition, natural products exhibit unique value in interventional therapy, such as serving as sensitizers or adjunctive therapy drugs during interventional radiation therapy, which helps to improve treatment efficacy and reduce side effects [170]. This comprehensive treatment model uses natural products as supplements or adjuncts to comprehensively apply in the overall treatment strategy of HCC, to achieve better treatment effects and improve patient survival rate.…”

“…In searching for treatment options for patients with HCC, we utilize targeted therapy to identify potential natural product drug candidates. The goal is to precisely target the genes associated with HCC, characterize ligandtarget protein interactions, and validate the selected ligand as a potential drug candidate [170]. This approach offers an efficient means of screening target genes in HCC research, leveraging the benefits of time-savings and selective treatment with precise targeting of HCC.…”

Underlying Mechanisms of Bergenia spp. to Treat Hepatocellular Carcinoma Using an Integrated Network Pharmacology and Molecular Docking Approach

“…The molecular docking study identifies the ligand–target protein interactions to verify the potential of selected ligands as drug candidates [ 45 ]. The results of network pharmacology and the potential of selected phytochemicals were further confirmed by the molecular docking approach.…”