Methotrexate, an anti-inflammatory drug, inhibits Hepatitis E viral replication
AbstractHepatitis E Virus (HEV) is a positively oriented RNA virus having a 7.2 kb genome. HEV consists of three open reading frames (ORF1-3). Of these, ORF1 codes for the enzymes Methyltransferase (Mtase), Papain-like cysteine protease (PCP), RNA helicase, and RNA-dependent RNA polymerase (RdRp). U...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2280500 |
| _version_ | 1797400978857656320 |
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| author | Akash Kumar Preeti Hooda Anindita Puri Radhika Khatter Mohammed S. Al-Dosari Neha Sinha Mohammad K. Parvez Deepak Sehgal |
| author_facet | Akash Kumar Preeti Hooda Anindita Puri Radhika Khatter Mohammed S. Al-Dosari Neha Sinha Mohammad K. Parvez Deepak Sehgal |
| author_sort | Akash Kumar |
| collection | DOAJ |
| description | AbstractHepatitis E Virus (HEV) is a positively oriented RNA virus having a 7.2 kb genome. HEV consists of three open reading frames (ORF1-3). Of these, ORF1 codes for the enzymes Methyltransferase (Mtase), Papain-like cysteine protease (PCP), RNA helicase, and RNA-dependent RNA polymerase (RdRp). Unavailability of a vaccine or effective drug against HEV and considering the side effects associated with the off-label use of ribavirin (RBV) and pegylated interferons, an alternative approach is required by the modulation of specific enzymes to prevent the infection. HEV helicase is involved in unwinding the double-stranded RNA, RNA processing, transcriptional regulation, and pre-mRNA processing. Therefore, we screened FDA-approved compounds from the ZINC15 database against the modelled 3D structure of HEV helicase and found that methotrexate and compound A (Pubchem ID BTB07890) inhibit the NTPase and dsRNA unwinding activity leading to inhibition of HEV RNA replication. This may be further authenticated by in vivo study. |
| first_indexed | 2024-03-09T02:03:17Z |
| format | Article |
| id | doaj.art-ebbdb346923c4ef9be783f2fa3d76e6e |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-09T02:03:17Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-ebbdb346923c4ef9be783f2fa3d76e6e2023-12-08T03:24:21ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2280500Methotrexate, an anti-inflammatory drug, inhibits Hepatitis E viral replicationAkash Kumar0Preeti Hooda1Anindita Puri2Radhika Khatter3Mohammed S. Al-Dosari4Neha Sinha5Mohammad K. Parvez6Deepak Sehgal7Department of Life Sciences, Virology lab, Shiv Nadar Institution of Eminence, Greater Noida, IndiaDepartment of Life Sciences, Virology lab, Shiv Nadar Institution of Eminence, Greater Noida, IndiaDepartment of Life Sciences, Virology lab, Shiv Nadar Institution of Eminence, Greater Noida, IndiaDepartment of Life Sciences, Virology lab, Shiv Nadar Institution of Eminence, Greater Noida, IndiaDepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USADepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Life Sciences, Virology lab, Shiv Nadar Institution of Eminence, Greater Noida, IndiaAbstractHepatitis E Virus (HEV) is a positively oriented RNA virus having a 7.2 kb genome. HEV consists of three open reading frames (ORF1-3). Of these, ORF1 codes for the enzymes Methyltransferase (Mtase), Papain-like cysteine protease (PCP), RNA helicase, and RNA-dependent RNA polymerase (RdRp). Unavailability of a vaccine or effective drug against HEV and considering the side effects associated with the off-label use of ribavirin (RBV) and pegylated interferons, an alternative approach is required by the modulation of specific enzymes to prevent the infection. HEV helicase is involved in unwinding the double-stranded RNA, RNA processing, transcriptional regulation, and pre-mRNA processing. Therefore, we screened FDA-approved compounds from the ZINC15 database against the modelled 3D structure of HEV helicase and found that methotrexate and compound A (Pubchem ID BTB07890) inhibit the NTPase and dsRNA unwinding activity leading to inhibition of HEV RNA replication. This may be further authenticated by in vivo study.https://www.tandfonline.com/doi/10.1080/14756366.2023.2280500Hepatitis E virushelicaseRNA replicationantiviralmethotrexate |
| spellingShingle | Akash Kumar Preeti Hooda Anindita Puri Radhika Khatter Mohammed S. Al-Dosari Neha Sinha Mohammad K. Parvez Deepak Sehgal Methotrexate, an anti-inflammatory drug, inhibits Hepatitis E viral replication Journal of Enzyme Inhibition and Medicinal Chemistry Hepatitis E virus helicase RNA replication antiviral methotrexate |
| title | Methotrexate, an anti-inflammatory drug, inhibits Hepatitis E viral replication |
| title_full | Methotrexate, an anti-inflammatory drug, inhibits Hepatitis E viral replication |
| title_fullStr | Methotrexate, an anti-inflammatory drug, inhibits Hepatitis E viral replication |
| title_full_unstemmed | Methotrexate, an anti-inflammatory drug, inhibits Hepatitis E viral replication |
| title_short | Methotrexate, an anti-inflammatory drug, inhibits Hepatitis E viral replication |
| title_sort | methotrexate an anti inflammatory drug inhibits hepatitis e viral replication |
| topic | Hepatitis E virus helicase RNA replication antiviral methotrexate |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2280500 |
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