Blog
About

0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Posaconazole is a novel inhibitor for alphavirus viral entry

      Read this article at

      ScienceOpenPublisher
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes millions of infection globally. Posaconazole (PCZ) is an antifungal drug, which we and others have previously found to inhibit replication of a number of viruses, including dengue virus, a member of the Flaviviridae family. In this study, we analyzed the antiviral activity of PCZ against alphaviruses. We found that PCZ potently inhibits a number of alphaviruses, including Semliki forest virus (SFV), Sindbis virus (SINV) and CHIKV with half maximal effective concentration (EC50) of 2.3 μM, 4.0 μM and 0.8 μM, respectively. Time-of-addition assays indicated that PCZ treatment before and at the time of SFV infection showed potent inhibition, whereas addition of PCZ at later time points post infection showed minor to no inhibition, suggesting inhibition at an early stage of the replication cycle. In accordance, PCZ treatment of a temperature sensitive mutant of SFV that is capable of cell entry and translation, but not RNA replication, resulted in an almost 90% reduction in luciferase activity. To confirm these findings, PCZ resistant mutant virus were generated and we identified mutations in E1 (V148A) and E2 (H255R) viral glycoproteins, of which the E2 mutation confers partial resistance to PCZ when introduced into wild-type SFV. To see whether PCZ alters clathrin-mediated endocytosis, we analyzed the uptake of fluorescence-tagged transferrin and found that PCZ reduced transferrin uptake by 50% compared to DMSO-treated cells. Together, these results establish PCZ as a novel inhibitor of alphaviruses and identify viral entry as its target.

          Related collections

          Author and article information

          Journal
          Access Microbiology
          acmi
          acmi
          Access Microbiology
          acmi
          Microbiology Society
          2516-8290
          December 2019
          20 December 2019
          : 1
          : 10
          Affiliations
          Radboud Institute for Molecular Life Sciences , Radboudumc, Nijmegen
          Institute of Technology , University of Tartu, Tartu
          Author notes
          * Correspondence: Febrina Meutiawati, febrinameutia@ 123456gmail.com
          Article
          acmi.imav2019.po0027
          10.1099/acmi.imav2019.po0027
          © 2019 The Authors

          This is an open-access article distributed under the terms of the Creative Commons Attribution License.

          Categories
          Poster
          Abstracts from the International Meeting on Arboviruses and their Vectors 2019
          Custom metadata
          0

          Comments

          Comment on this article