Miltefosine inhibits Chikungunya virus replication in human primary dermal fibroblasts [version 1; referees: 2 approved, 1 approved with reservations]
Background: Chikungunya virus (CHIKV) is a re-emerging pathogen that has caused widespread outbreaks affecting millions of people around the globe. Currently, there is no specific therapeutic drug against CHIKV, with symptomatic treatment only to manage the disease. Pi3-akt signaling has been implic...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2018-01-01
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| Series: | F1000Research |
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| Online Access: | https://f1000research.com/articles/7-9/v1 |
| _version_ | 1818203491155312640 |
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| author | Anuj Sharma Manish Bhomia Tze-Jou Yeh Jay Singh Radha K. Maheshwari |
| author_facet | Anuj Sharma Manish Bhomia Tze-Jou Yeh Jay Singh Radha K. Maheshwari |
| author_sort | Anuj Sharma |
| collection | DOAJ |
| description | Background: Chikungunya virus (CHIKV) is a re-emerging pathogen that has caused widespread outbreaks affecting millions of people around the globe. Currently, there is no specific therapeutic drug against CHIKV, with symptomatic treatment only to manage the disease. Pi3-akt signaling has been implicated in infection of several viruses including that of CHIKV. Effect of Pi3-akt signaling inhibitors on CHIKV replication was evaluated in this study. Methods: Human primary dermal fibroblast cells were treated with inhibitors of the Pi3-akt signaling pathway. Suppression of CHIKV replication was evaluated as reduction in virus titer in cell supernatants. Effect of miltefosine (MF) on CHIKV replication was evaluated in pre and post treatment regimen. Inhibition of virus replication was determined by cell growth, virus titer and western blot. Results: Inhibition of Akt-phosphorylation significantly inhibited CHIKV replication. No effect on CHIKV replication was observed after treatment with Pi3-kinase and mTOR activation inhibitors. Further, MF, an FDA-approved Akt-inhibitor, inhibited CHIKV replication in pre- and post-infection treatment regimens. Conclusion: Data suggests that Akt-phosphorylation can be an amenable target of therapy against CHIKV infection. This is the first study to show inhibition of CHIKV replication by MF, and presents a case for further development of MF as an anti-CHIKV drug. |
| first_indexed | 2024-12-12T03:26:11Z |
| format | Article |
| id | doaj.art-043764fa86dc40b18f7eb6b82de7f4ed |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-12T03:26:11Z |
| publishDate | 2018-01-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-043764fa86dc40b18f7eb6b82de7f4ed2022-12-22T00:40:02ZengF1000 Research LtdF1000Research2046-14022018-01-01710.12688/f1000research.13242.114366Miltefosine inhibits Chikungunya virus replication in human primary dermal fibroblasts [version 1; referees: 2 approved, 1 approved with reservations]Anuj Sharma0Manish Bhomia1Tze-Jou Yeh2Jay Singh3Radha K. Maheshwari4Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USADepartment of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USADepartment of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USADepartment of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USADepartment of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USABackground: Chikungunya virus (CHIKV) is a re-emerging pathogen that has caused widespread outbreaks affecting millions of people around the globe. Currently, there is no specific therapeutic drug against CHIKV, with symptomatic treatment only to manage the disease. Pi3-akt signaling has been implicated in infection of several viruses including that of CHIKV. Effect of Pi3-akt signaling inhibitors on CHIKV replication was evaluated in this study. Methods: Human primary dermal fibroblast cells were treated with inhibitors of the Pi3-akt signaling pathway. Suppression of CHIKV replication was evaluated as reduction in virus titer in cell supernatants. Effect of miltefosine (MF) on CHIKV replication was evaluated in pre and post treatment regimen. Inhibition of virus replication was determined by cell growth, virus titer and western blot. Results: Inhibition of Akt-phosphorylation significantly inhibited CHIKV replication. No effect on CHIKV replication was observed after treatment with Pi3-kinase and mTOR activation inhibitors. Further, MF, an FDA-approved Akt-inhibitor, inhibited CHIKV replication in pre- and post-infection treatment regimens. Conclusion: Data suggests that Akt-phosphorylation can be an amenable target of therapy against CHIKV infection. This is the first study to show inhibition of CHIKV replication by MF, and presents a case for further development of MF as an anti-CHIKV drug.https://f1000research.com/articles/7-9/v1Viral Infections (without HIV) |
| spellingShingle | Anuj Sharma Manish Bhomia Tze-Jou Yeh Jay Singh Radha K. Maheshwari Miltefosine inhibits Chikungunya virus replication in human primary dermal fibroblasts [version 1; referees: 2 approved, 1 approved with reservations] F1000Research Viral Infections (without HIV) |
| title | Miltefosine inhibits Chikungunya virus replication in human primary dermal fibroblasts [version 1; referees: 2 approved, 1 approved with reservations] |
| title_full | Miltefosine inhibits Chikungunya virus replication in human primary dermal fibroblasts [version 1; referees: 2 approved, 1 approved with reservations] |
| title_fullStr | Miltefosine inhibits Chikungunya virus replication in human primary dermal fibroblasts [version 1; referees: 2 approved, 1 approved with reservations] |
| title_full_unstemmed | Miltefosine inhibits Chikungunya virus replication in human primary dermal fibroblasts [version 1; referees: 2 approved, 1 approved with reservations] |
| title_short | Miltefosine inhibits Chikungunya virus replication in human primary dermal fibroblasts [version 1; referees: 2 approved, 1 approved with reservations] |
| title_sort | miltefosine inhibits chikungunya virus replication in human primary dermal fibroblasts version 1 referees 2 approved 1 approved with reservations |
| topic | Viral Infections (without HIV) |
| url | https://f1000research.com/articles/7-9/v1 |
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