Exploring the antiviral activities of the FDA-approved drug sulfadoxine and its derivatives against Chikungunya virus.

Autor: Martins DOS; Institute of Biomedical Science - ICBIM, Federal University of Uberlândia - UFU, Avenida Amazonas, 4C- Room 216, Umuarama, Uberlândia, MG, CEP: 38405-302, Brazil.; Institute of Bioscience, Language and Exact Sciences - IBILCE, São Paulo State University - UNESP, São José do Rio Preto, SP, Brazil., Ruiz UEA; Institute of Biomedical Science - ICBIM, Federal University of Uberlândia - UFU, Avenida Amazonas, 4C- Room 216, Umuarama, Uberlândia, MG, CEP: 38405-302, Brazil., Santos IA; Institute of Biomedical Science - ICBIM, Federal University of Uberlândia - UFU, Avenida Amazonas, 4C- Room 216, Umuarama, Uberlândia, MG, CEP: 38405-302, Brazil., Oliveira IS; Institute of Chemistry, University of Campinas - UNICAMP, Campinas, SP, Brazil., Guevara-Vega M; Institute of Biomedical Science - ICBIM, Federal University of Uberlândia - UFU, Avenida Amazonas, 4C- Room 216, Umuarama, Uberlândia, MG, CEP: 38405-302, Brazil., de Paiva REF; Donostia International Physics Center- DIPC, Paseo Manuel de Lardizabal 4, 20018 Donostia, Euskadi, Gipuzkoa, Spain., Abbehausen C; Institute of Chemistry, University of Campinas - UNICAMP, Campinas, SP, Brazil., Sabino-Silva R; Institute of Biomedical Science - ICBIM, Federal University of Uberlândia - UFU, Avenida Amazonas, 4C- Room 216, Umuarama, Uberlândia, MG, CEP: 38405-302, Brazil., Corbi PP; Institute of Chemistry, University of Campinas - UNICAMP, Campinas, SP, Brazil., Jardim ACG; Institute of Biomedical Science - ICBIM, Federal University of Uberlândia - UFU, Avenida Amazonas, 4C- Room 216, Umuarama, Uberlândia, MG, CEP: 38405-302, Brazil. jardim@ufu.br.; Institute of Bioscience, Language and Exact Sciences - IBILCE, São Paulo State University - UNESP, São José do Rio Preto, SP, Brazil. jardim@ufu.br.
Jazyk: angličtina
Zdroj: Pharmacological reports : PR [Pharmacol Rep] 2024 Aug 16. Date of Electronic Publication: 2024 Aug 16.
DOI: 10.1007/s43440-024-00635-z
Abstrakt: Background: Currently, there is no antiviral licensed to treat chikungunya fever, a disease caused by the infection with Alphavirus chikungunya (CHIKV). Treatment is based on analgesic and anti-inflammatory drugs to relieve symptoms. Our study aimed to evaluate the antiviral activity of sulfadoxine (SFX), an FDA-approved drug, and its derivatives complexed with silver(I) (AgSFX), salicylaldehyde Schiff base (SFX-SL), and with both Ag and SL (AgSFX-SL) against CHIKV.
Methods: The anti-CHIKV activity of SFX and its derivatives was investigated using BHK-21 cells infected with CHIKV-nanoluc, a marker virus-carrying nanoluciferase reporter. Dose-response and time of drug-addition assays were performed in order to assess the antiviral effects of the compounds, as well as in silico data and ATR-FTIR analysis for insights on their mechanisms of action.
Results: The SFX inhibited 34% of CHIKV replication, while AgSFX, SFX-SL, and AgSFX-SL enhanced anti-CHIKV activity to 84%, 89%, and 95%, respectively. AgSFX, SFX-SL, and AgSFX-SL significantly decreased viral entry and post-entry to host cells, and the latter also protected cells against infection. Additionally, molecular docking calculations and ATR-FTIR analysis demonstrated interactions of SFX-SL, AgSFX, and AgSFX-SL with CHIKV.
Conclusions: Collectively, our findings suggest that the addition of metal ions and/or Schiff base to SFX improved its antiviral activity against CHIKV.
(© 2024. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)
Databáze: MEDLINE
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