Antiviral Activity and Molecular Dynamics Simulation of Hops Compounds against Oropouche Virus (<i>Peribunyaviridae</i>)
Tsvetelina Mandova,
Marielena Vogel Saivish,
Gabriela de Lima Menezes,
Katyanna Sales Bezerra,
Umberto Laino Fulco,
Roosevelt Alves da Silva,
Fernando Batista Da Costa,
Maurício Lacerda Nogueira
Affiliations
Tsvetelina Mandova
AsterBioChem Research Team, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-020, SP, Brazil
Marielena Vogel Saivish
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
Gabriela de Lima Menezes
Bioinformatics Multidisciplinary Environment, Programa de Pós Graduação em Bioinformática, Universidade Federal do Rio Grande do Norte, Natal 59078-400, RN, Brazil
Katyanna Sales Bezerra
Bioinformatics Multidisciplinary Environment, Programa de Pós Graduação em Bioinformática, Universidade Federal do Rio Grande do Norte, Natal 59078-400, RN, Brazil
Umberto Laino Fulco
Bioinformatics Multidisciplinary Environment, Programa de Pós Graduação em Bioinformática, Universidade Federal do Rio Grande do Norte, Natal 59078-400, RN, Brazil
Roosevelt Alves da Silva
Núcleo Colaborativo de Biosistemas, Universidade Federal de Jataí, Jataí 75801-615, GO, Brazil
Fernando Batista Da Costa
AsterBioChem Research Team, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-020, SP, Brazil
Maurício Lacerda Nogueira
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
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 (EC50 = 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.
