Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening
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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/6/2675 |
| _version_ | 1797609888423084032 |
|---|---|
| author | Ghulam Mustafa Hafiza Salaha Mahrosh Syed Awais Attique Rawaba Arif Mohammad Abul Farah Khalid Mashay Al-Anazi Sajad Ali |
| author_facet | Ghulam Mustafa Hafiza Salaha Mahrosh Syed Awais Attique Rawaba Arif Mohammad Abul Farah Khalid Mashay Al-Anazi Sajad Ali |
| author_sort | Ghulam Mustafa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T06:07:53Z |
| format | Article |
| id | doaj.art-e748c2a58d724b1fa388278148690cde |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T06:07:53Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-e748c2a58d724b1fa388278148690cde2023-11-17T12:53:37ZengMDPI AGMolecules1420-30492023-03-01286267510.3390/molecules28062675Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual ScreeningGhulam Mustafa0Hafiza Salaha Mahrosh1Syed Awais Attique2Rawaba Arif3Mohammad Abul Farah4Khalid Mashay Al-Anazi5Sajad Ali6Department of Biochemistry, Government College University Faisalabad, Faisalabad 38000, PakistanDepartment of Biochemistry, University of Agriculture Faisalabad, Faisalabad 38000, PakistanSchool of Interdisciplinary Engineering & Science (SINES), National University of Sciences & Technology (NUST), Islamabad 44000, PakistanDepartment of Biochemistry, University of Jhang, Jhang 35200, PakistanDepartment of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of KoreaHepatitis 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.https://www.mdpi.com/1420-3049/28/6/2675capsid proteinEDGEMD simulationmolecular dockingORF2TDGH |
| spellingShingle | Ghulam Mustafa Hafiza Salaha Mahrosh Syed Awais Attique Rawaba Arif Mohammad Abul Farah Khalid Mashay Al-Anazi Sajad Ali Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening Molecules capsid protein EDGE MD simulation molecular docking ORF2 TDGH |
| title | Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening |
| title_full | Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening |
| title_fullStr | Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening |
| title_full_unstemmed | Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening |
| title_short | Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening |
| title_sort | identification of plant peptides as novel inhibitors of orthohepevirus a hev capsid protein by virtual screening |
| topic | capsid protein EDGE MD simulation molecular docking ORF2 TDGH |
| url | https://www.mdpi.com/1420-3049/28/6/2675 |
| work_keys_str_mv | AT ghulammustafa identificationofplantpeptidesasnovelinhibitorsoforthohepevirusahevcapsidproteinbyvirtualscreening AT hafizasalahamahrosh identificationofplantpeptidesasnovelinhibitorsoforthohepevirusahevcapsidproteinbyvirtualscreening AT syedawaisattique identificationofplantpeptidesasnovelinhibitorsoforthohepevirusahevcapsidproteinbyvirtualscreening AT rawabaarif identificationofplantpeptidesasnovelinhibitorsoforthohepevirusahevcapsidproteinbyvirtualscreening AT mohammadabulfarah identificationofplantpeptidesasnovelinhibitorsoforthohepevirusahevcapsidproteinbyvirtualscreening AT khalidmashayalanazi identificationofplantpeptidesasnovelinhibitorsoforthohepevirusahevcapsidproteinbyvirtualscreening AT sajadali identificationofplantpeptidesasnovelinhibitorsoforthohepevirusahevcapsidproteinbyvirtualscreening |