Computational structure-based design of antiviral peptides as potential protein–protein interaction inhibitors of rabies virus phosphoprotein and human LC8
Rabies is a serious zoonotic disease caused by the rabies virus (RABV). Despite the successful development of vaccines and efforts made in drug discovery, rabies is incurable. Therefore, development of novel drugs is of interest to the scientific community. Antiviral peptides can be designed based o...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024175512 |
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| author | Saman Rahmati Fatemeh Zandi Khadijeh Ahmadi Ahmad Adeli Niloofar Rastegarpanah Massoud Amanlou Behrouz Vaziri |
| author_facet | Saman Rahmati Fatemeh Zandi Khadijeh Ahmadi Ahmad Adeli Niloofar Rastegarpanah Massoud Amanlou Behrouz Vaziri |
| author_sort | Saman Rahmati |
| collection | DOAJ |
| description | Rabies is a serious zoonotic disease caused by the rabies virus (RABV). Despite the successful development of vaccines and efforts made in drug discovery, rabies is incurable. Therefore, development of novel drugs is of interest to the scientific community. Antiviral peptides can be designed based on the known structures of viral proteins and their biological targets. Cytoplasmic dynein light chain LC8, one of the first identified host partners of RABV phosphoprotein (RABV P), is an essential factor for RABV transcription and replication. As part of the search for new potential drugs against rabies, we used structure-based drug design using the in silico tools. The binding site of LC8 with RABV P was used for peptide design. Four potential peptide inhibitors (Pep1-4) were selected, modeled, and docked with RABV P. The highest binding affinity was observed for the RABV P-Pep2 complex. Molecular dynamics (MD) simulations were performed and the stability of the peptides and complexes was confirmed. Finally, Pep2 can be used as a potential candidate for peptide-based antiviral therapy against RABV. The identified small peptides may prevent RABV infection based on the results of the current investigation. Further in vitro and in vivo studies are needed to confirm these results. |
| format | Article |
| id | doaj-art-919e77532d384f6daf6b97106c3c4bb1 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-919e77532d384f6daf6b97106c3c4bb12025-01-17T04:51:31ZengElsevierHeliyon2405-84402025-01-01111e41520Computational structure-based design of antiviral peptides as potential protein–protein interaction inhibitors of rabies virus phosphoprotein and human LC8Saman Rahmati0Fatemeh Zandi1Khadijeh Ahmadi2Ahmad Adeli3Niloofar Rastegarpanah4Massoud Amanlou5Behrouz Vaziri6Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran; Division of Oncological Sciences, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USABiotechnology Research Center, Pasteur Institute of Iran, Tehran, IranDepartment of Medical Biotechnology, School of Paramedicine, Bushehr University of Medical Sciences, Bushehr, IranBiotechnology Research Center, Pasteur Institute of Iran, Tehran, IranDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Corresponding author. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O.Box 14155-6451, Tehran, Iran.Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran; Corresponding author. Protein Chemistry Unit, Biotechnology Research Center, Pasteur Institute of Iran, 69, Pasteur St, 13164, Tehran, Iran.Rabies is a serious zoonotic disease caused by the rabies virus (RABV). Despite the successful development of vaccines and efforts made in drug discovery, rabies is incurable. Therefore, development of novel drugs is of interest to the scientific community. Antiviral peptides can be designed based on the known structures of viral proteins and their biological targets. Cytoplasmic dynein light chain LC8, one of the first identified host partners of RABV phosphoprotein (RABV P), is an essential factor for RABV transcription and replication. As part of the search for new potential drugs against rabies, we used structure-based drug design using the in silico tools. The binding site of LC8 with RABV P was used for peptide design. Four potential peptide inhibitors (Pep1-4) were selected, modeled, and docked with RABV P. The highest binding affinity was observed for the RABV P-Pep2 complex. Molecular dynamics (MD) simulations were performed and the stability of the peptides and complexes was confirmed. Finally, Pep2 can be used as a potential candidate for peptide-based antiviral therapy against RABV. The identified small peptides may prevent RABV infection based on the results of the current investigation. Further in vitro and in vivo studies are needed to confirm these results.http://www.sciencedirect.com/science/article/pii/S2405844024175512RABV phosphoproteinLC8Antiviral peptidesDockingMolecular dynamics simulation |
| spellingShingle | Saman Rahmati Fatemeh Zandi Khadijeh Ahmadi Ahmad Adeli Niloofar Rastegarpanah Massoud Amanlou Behrouz Vaziri Computational structure-based design of antiviral peptides as potential protein–protein interaction inhibitors of rabies virus phosphoprotein and human LC8 Heliyon RABV phosphoprotein LC8 Antiviral peptides Docking Molecular dynamics simulation |
| title | Computational structure-based design of antiviral peptides as potential protein–protein interaction inhibitors of rabies virus phosphoprotein and human LC8 |
| title_full | Computational structure-based design of antiviral peptides as potential protein–protein interaction inhibitors of rabies virus phosphoprotein and human LC8 |
| title_fullStr | Computational structure-based design of antiviral peptides as potential protein–protein interaction inhibitors of rabies virus phosphoprotein and human LC8 |
| title_full_unstemmed | Computational structure-based design of antiviral peptides as potential protein–protein interaction inhibitors of rabies virus phosphoprotein and human LC8 |
| title_short | Computational structure-based design of antiviral peptides as potential protein–protein interaction inhibitors of rabies virus phosphoprotein and human LC8 |
| title_sort | computational structure based design of antiviral peptides as potential protein protein interaction inhibitors of rabies virus phosphoprotein and human lc8 |
| topic | RABV phosphoprotein LC8 Antiviral peptides Docking Molecular dynamics simulation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024175512 |
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