2. Academic Validation
  3. Acridones as promising drug candidates against Oropouche virus

Acridones as promising drug candidates against Oropouche virus

  • Curr Res Microb Sci. 2023 Dec 23:6:100217. doi: 10.1016/j.crmicr.2023.100217.
Marielena Vogel Saivish 1,  Gabriela de Lima Menezes 2 3,  Roosevelt Alves da Silva 2,  Leticia Ribeiro de Assis 4,  Igor da Silva Teixeira 1,  Umberto Laino Fulco 3,  Clarita Maria Secco Avilla 1 4,  Raphael Josef Eberle 5 6,  Igor de Andrade Santos 7,  Karolina Korostov 5,  Mayara Lucia Webber 1,  Gislaine Celestino Dutra da Silva 1,  Maurício Lacerda Nogueira 1,  Ana Carolina Gomes Jardim 4 7,  Luis Octavio Regasin 4,  Mônika Aparecida Coronado 5,  Carolina Colombelli Pacca 1 4
Affiliations

Affiliations

  • 1 Laboratório 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, SP 15090-000, Brazil.
  • 2 Unidade Especial de Ciências Exatas, Universidade Federal de Jataí, Jataí, GO 75801-615, Brazil.
  • 3 Bioinformatics Multidisciplinary Environment, Programa de Pós-graduação em Bioinformática, Universidade Federal do Rio Grande do Norte, Natal 59078-400, RN, Brazil.
  • 4 Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University, São José do Rio Preto, SP 15054-000, Brazil.
  • 5 Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, Jülich 52428, Germany.
  • 6 Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Physical Biology, Universitätsstraße, Düsseldorf 40225, Germany.
  • 7 Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia-MG 38405-302, Brazil.
PMID: 38234431 DOI: 10.1016/j.crmicr.2023.100217
Abstract

Oropouche virus (OROV) is an emerging vector-borne arbovirus found in South America that causes Oropouche fever, a febrile Infection similar to dengue fever. It has a high epidemic potential, causing illness in over 500,000 cases diagnosed since the virus was first discovered in 1955. Currently, the prevention of human viral Infection depends on vaccination, but availability for many viruses is limited, and they are classified as neglected viruses. At present, there are no vaccines or Antiviral treatments available. An alternative approach to limiting the spread of the virus is to selectively disrupt viral replication mechanisms. Here, we demonstrate the inhibitory effect of acridones, which efficiently inhibited viral replication by 99.9 % in vitro. To evaluate possible mechanisms of action, we conducted tests with dsRNA, an intermediate in virus replication, as well as MD simulations, docking, and binding free energy analysis. The results showed a strong interaction between FAC21 and the OROV Endonuclease, which possibly limits the interaction of viral RNA with Other proteins. Therefore, our results suggest a dual mechanism of Antiviral action, possibly caused by ds-RNA intercalation. In summary, our findings demonstrate that a new generation of Antiviral drugs could be developed based on the selective optimization of molecules.

Keywords

Acridone; Antiviral; Drug discovery; Endonuclease; Oropouche.

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