| Autor: |
Mandova T; AsterBioChem Research Team, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-020, SP, Brazil.; Gilson Purification, 22 rue Bourseul, 56890 Saint Avé, France., Saivish MV; Laboratórios de Pesquisas em Virologia, Departamento de Doenças Dermatológicas, Infecciosas e Parasitárias, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto 15090-000, SP, Brazil.; Brazilian Biosciences National Laboratory, Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas 13083-100, SP, Brazil., Menezes GL; Bioinformatics Multidisciplinary Environment, Programa de Pós Graduação em Bioinformática, Universidade Federal do Rio Grande do Norte, Natal 59078-400, RN, Brazil., Bezerra KS; Bioinformatics Multidisciplinary Environment, Programa de Pós Graduação em Bioinformática, Universidade Federal do Rio Grande do Norte, Natal 59078-400, RN, Brazil., Fulco UL; Bioinformatics Multidisciplinary Environment, Programa de Pós Graduação em Bioinformática, Universidade Federal do Rio Grande do Norte, Natal 59078-400, RN, Brazil., da Silva RA; Núcleo Colaborativo de Biosistemas, Universidade Federal de Jataí, Jataí 75801-615, GO, Brazil., Da Costa FB; AsterBioChem Research Team, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-020, SP, Brazil., Nogueira ML; Laboratórios de Pesquisas em Virologia, Departamento de Doenças Dermatológicas, Infecciosas e Parasitárias, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto 15090-000, SP, Brazil.; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. |
| Abstrakt: |
The Oropouche virus (OROV) is a member of the family Peribunyaviridae (order Bunyavirales ) and the cause of a dengue-like febrile illness transmitted mainly by biting midges and mosquitoes. In this study, we aimed to explore acylphloroglucinols and xanthohumol from hops ( Humulus lupulus L.) as a promising alternative for antiviral therapies. The evaluation of the inhibitory potential of hops compounds on the viral cycle of OROV was performed through two complementary approaches. The first approach applies cell-based assay post-inoculation experiments to explore the inhibitory potential on the latest steps of the viral cycle, such as genome translation, replication, virion assembly, and virion release from the cells. The second part covers in silico methods evaluating the ability of those compounds to inhibit the activity of the endonuclease domain, which is essential for transcription, binding, and cleaving RNA. In conclusion, the beta acids showed strongest inhibitory potential in post-treatment assay (EC 50 = 26.7 µg/mL). Xanthohumol had the highest affinity for OROV endonuclease followed by colupulone and cohumulone. This result contrasts with that observed for docking and MM/PBSA analysis, where cohumulone was found to have a higher affinity. Finally, among the three tested ligands, Lys92 and Arg33 exhibited the highest affinity with the protein. |
