Miltefosine inhibits Chikungunya virus replication in human

Chikungunya virus (CHIKV) is a re-emerging pathogen that has Background 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. : Human primary dermal fibroblast cells were treated with inhibitors of Methods 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. : Inhibition of Akt-phosphorylation significantly inhibited CHIKV Results 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 preand post-infection treatment regimens. : Data suggests that Akt-phosphorylation can be an amenable Conclusion 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. Anuj Sharma ( ) Corresponding author: [email protected] : Conceptualization, Data Curation, Formal Analysis, Methodology, Project Administration, Supervision, Writing – Original Author roles: Sharma A Draft Preparation, Writing – Review & Editing; : Methodology; : Methodology; : Methodology; : Funding Bhomia M Yeh TJ Singh J Maheshwari RK Acquisition, Project Administration, Supervision, Writing – Original Draft Preparation No competing interests were disclosed. Competing interests: Sharma A, Bhomia M, Yeh TJ How to cite this article: et al. Miltefosine inhibits Chikungunya virus replication in human primary dermal 2018, :9 (doi: ) fibroblasts [version 1; referees: 1 approved] F1000Research 7 10.12688/f1000research.13242.1 © 2018 Sharma A . This is an open access article distributed under the terms of the , which Copyright: et al Creative Commons Attribution Licence permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the (CC0 1.0 Public domain dedication). Creative Commons Zero "No rights reserved" data waiver This study was funded by a grant from Defense Threat Reduction Agency. Grant information: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 04 Jan 2018, :9 (doi: ) First published: 7 10.12688/f1000research.13242.1 +