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Acridones as promising drug candidates against Oropouche virus

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Saivish, Marielena Vogel ; Menezes, Gabriela de Lima ; da Silva, Roosevelt Alves ; de Assis, Leticia Ribeiro ; Teixeira, Igor da Silva ; Fulco, Umberto Laino ; Avilla, Clarita Maria Secco ; Eberle, Raphael Josef ; Santos, Igor de Andrade ; Korostov, Karolina ; Webber, Mayara Lucia ; da Silva, Gislaine Celestino Dutra ; Nogueira, Mauricio Lacerda ; Jardim, Ana Carolina Gomes ; Regasin, Luis Octavio ; Coronado, Monika Aparecida ; Pacca, Carolina Colombelli
Total Authors: 17
Document type: Journal article
Source: CURRENT RESEARCH IN MICROBIAL SCIENCES; v. 6, p. 11-pg., 2023-12-31.
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. (AU)

FAPESP's process: 23/09590-7 - Development of a diagnostic method for the rocio virus and the use of new compounds as inhibitors of the flavivirus NS2B-NS3 protease-helicase
Grantee:Marielena Vogel Saivish
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 18/15083-2 - Synthesis and biological evaluation of isobavachalcone (IBC) and analogs as potential agents against tuberculosis
Grantee:Luis Octávio Regasini
Support Opportunities: Regular Research Grants
FAPESP's process: 20/12875-5 - Development of the diagnostic method for Rocio virus and use of new compounds as inhibitors of flavivirus protease-helicase NS2B-NS3
Grantee:Marielena Vogel Saivish
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 13/21719-3 - Epidemiological study of dengue (serotypes1-4) in a cohort of São José do Rio Preto, São Paulo, Brazil, during 2014-2018
Grantee:Maurício Lacerda Nogueira
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 17/13341-1 - Search of compounds and peptides with potential antiviral activity against Arbovirus of clinical importance
Grantee:Carolina Colombelli Pacca
Support Opportunities: Regular Research Grants