TY  - JOUR
AU  - Saivish, Marielena Vogel
AU  - Menezes, Gabriela de Lima
AU  - da Silva, Roosevelt Alves
AU  - de Assis, Leticia Ribeiro
AU  - Teixeira, Igor da Silva
AU  - Fulco, Umberto Laino
AU  - Avilla, Clarita Maria Secco
AU  - Eberle, Raphael Josef
AU  - Santos, Igor de Andrade
AU  - Korostov, Karolina
AU  - Webber, Mayara Lucia
AU  - da Silva, Gislaine Celestino Dutra
AU  - Nogueira, Maurício Lacerda
AU  - Jardim, Ana Carolina Gomes
AU  - Regasin, Luis Octavio
AU  - Coronado, Mônika Aparecida
AU  - Pacca, Carolina Colombelli
TI  - Acridones as promising drug candidates against Oropouche virus
JO  - Current research in microbial sciences
VL  - 6
SN  - 2666-5174
CY  - Amsterdam
PB  - Elsevier B.V.
M1  - FZJ-2024-01308
SP  - 100217 -
PY  - 2024
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 38234431
UR  - <Go to ISI:>//WOS:001152529700001
DO  - DOI:10.1016/j.crmicr.2023.100217
UR  - https://juser.fz-juelich.de/record/1022187
ER  -