Thamires Rodrigues Freitas1, Raul Marques Novais1, Igor Andrade Santos2, Daniel Oliveira Silva Martins2,3, Amanda Danuello1, Vanderlan da Silva Bolzani4, Ana Carolina Gomes Jardim5,6, Marcos Pivatto7. 1. Núcleo de Pesquisa em Compostos Bioativos (NPCBio), Instituto de Química, Universidade Federal de Uberlândia, Uberlândia, MG, 38400-902, Brazil. 2. Laboratório de Pesquisa em Antivirais, Instituto de Ciências Biomédicas (ICBIM), Universidade Federal de Uberlândia, MG, 38405-317, Uberlândia, Brazil. 3. Universidade Estadual Paulista "Júlio de Mesquita Filho", São José Do Rio Preto, SP, 15054-000, Brazil. 4. Núcleo de Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE), Departamento de Química Orgânica, Instituto de Química, Universidade Estadual Paulista, P.O. Box 355, Araraquara, SP, 14801-970, Brazil. 5. Laboratório de Pesquisa em Antivirais, Instituto de Ciências Biomédicas (ICBIM), Universidade Federal de Uberlândia, MG, 38405-317, Uberlândia, Brazil. jardim@ufu.br. 6. Universidade Estadual Paulista "Júlio de Mesquita Filho", São José Do Rio Preto, SP, 15054-000, Brazil. jardim@ufu.br. 7. Núcleo de Pesquisa em Compostos Bioativos (NPCBio), Instituto de Química, Universidade Federal de Uberlândia, Uberlândia, MG, 38400-902, Brazil. pivatto@ufu.br.
Abstract
BACKGROUND: Chikungunya fever is an endemic disease caused by the Chikungunya virus (CHIKV). To date there is no antiviral treatment against this infection or licensed vaccine to prevent it. Our study aims to evaluate whether (-)-cassine (1) and (-)-spectaline (2), the main alkaloids of Senna spectabilis, display anti-CHIKV activity. Both compounds have been described to be biologically active against neglected tropical diseases, including malaria, leishmaniasis, and schistosomiasis, which emphasizes that these molecules could be repurposed for chikungunya fever treatment. METHODS: The structures of the isolated compounds 1 and 2 were identified by NMR and HRESIMS analyses, and their antiviral activity against CHIKV was assessed by a dose-response assay employing BHK-21 cells and CHIKV-nanoluc, a recombinant virus carrying the nanoluciferase gene reporter. RESULTS: Compound 1 presented CC50 of 126.5 µM and EC50 of 14.9 µM, while compound 2 presented CC50 of 91.9 µM and EC50 of 8.3 µM. The calculated selectivity index (SI) was 8.5 for 1 and 11.3 for 2. CONCLUSION: The data presented herein show that compounds 1 and 2 have potential for being repurposed as anti-CHIKV drug. Our promising in vitro results encourage further in vitro and in vivo assays. This is the first description of the antiviral activity of compounds 1 and 2 against CHIKV infection, which can impact the development of antiviral drug candidates against chikungunya fever, which sometimes can be debilitating.
BACKGROUND: Chikungunya fever is an endemic disease caused by the Chikungunya virus (CHIKV). To date there is no antiviral treatment against this infection or licensed vaccine to prevent it. Our study aims to evaluate whether (-)-cassine (1) and (-)-spectaline (2), the main alkaloids of Senna spectabilis, display anti-CHIKV activity. Both compounds have been described to be biologically active against neglected tropical diseases, including malaria, leishmaniasis, and schistosomiasis, which emphasizes that these molecules could be repurposed for chikungunya fever treatment. METHODS: The structures of the isolated compounds 1 and 2 were identified by NMR and HRESIMS analyses, and their antiviral activity against CHIKV was assessed by a dose-response assay employing BHK-21 cells and CHIKV-nanoluc, a recombinant virus carrying the nanoluciferase gene reporter. RESULTS: Compound 1 presented CC50 of 126.5 µM and EC50 of 14.9 µM, while compound 2 presented CC50 of 91.9 µM and EC50 of 8.3 µM. The calculated selectivity index (SI) was 8.5 for 1 and 11.3 for 2. CONCLUSION: The data presented herein show that compounds 1 and 2 have potential for being repurposed as anti-CHIKV drug. Our promising in vitro results encourage further in vitro and in vivo assays. This is the first description of the antiviral activity of compounds 1 and 2 against CHIKV infection, which can impact the development of antiviral drug candidates against chikungunya fever, which sometimes can be debilitating.
Authors: Roy Matkovic; Eric Bernard; Jean-Marie Péloponèse; Simon Fontanel; Patrick Eldin; Nathalie Chazal; Deka Hassan Hersi; Andres Merits; Laurence Briant Journal: J Virol Date: 2019-02-05 Impact factor: 5.103
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