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Evaluation of the antiviral activity of orlistat (tetrahydrolipstatin) against dengue virus, Japanese encephalitis virus, Zika virus and chikungunya virus

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  • Atitaya Hitakarun
  • Sarawut Khongwichit
  • Nitwara Wikan
  • Sittiruk Roytrakul
  • Sutee Yoksan
  • Supoth Rajakam
  • Andrew D. Davidson
  • Duncan R. Smith
Original languageEnglish
Article number1499 (2020)
Number of pages11
JournalScientific Reports
Volume10
Issue number1
DOIs
DateAccepted/In press - 15 Jan 2020
DatePublished (current) - 30 Jan 2020

Abstract

Many mosquito transmitted viruses of the genera Alphavirus and Flavivirus are human pathogens of significant concern, and there is currently no specific antiviral for any member of these two genera. This study sought to investigate the broad utility of orlistat (tetrahydrolipstatin) in reducing virus infection for several mosquito borne viruses including flaviviruses (dengue virus (DENV; nine isolates analyzed), Japanese encephalitis virus (JEV; one isolate analyzed) and Zika virus (ZIKV; 2 isolates analyzed)) as well as an alphavirus (chikungunya virus; CHIKV; 2 isolates analyzed). Three different treatment regimens were evaluated, namely pre-treatment (only), post-treatment (only) and pre- and post-treatment, and three factors were evaluated, namely level of infection, virus titer and genome copy number. Results showed that all three treatment modalities were able to significantly reduce virus titer for all viruses investigated, with the exception of three isolates of DENV in the pre-treatment only regimen. Pre- and post-treatment was more effective in reducing the level of infection and genome copy number of all viruses investigated than either pre-treatment or post-treatment alone. Collectively, these results suggest orlistat has potential as a broad-spectrum agent against multiple mosquito transmitted viruses.

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Springer Nature at https://www.nature.com/articles/s41598-020-58468-8. Please refer to any applicable terms of use of the publisher.

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