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001022187 0247_ $$2doi$$a10.1016/j.crmicr.2023.100217
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001022187 1001_ $$00000-0002-7627-621X$$aSaivish, Marielena Vogel$$b0
001022187 245__ $$aAcridones as promising drug candidates against Oropouche virus
001022187 260__ $$aAmsterdam$$bElsevier B.V.$$c2024
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001022187 520__ $$aOropouche 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.
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001022187 7001_ $$0P:(DE-HGF)0$$aMenezes, Gabriela de Lima$$b1
001022187 7001_ $$0P:(DE-HGF)0$$ada Silva, Roosevelt Alves$$b2
001022187 7001_ $$0P:(DE-HGF)0$$ade Assis, Leticia Ribeiro$$b3
001022187 7001_ $$0P:(DE-HGF)0$$aTeixeira, Igor da Silva$$b4
001022187 7001_ $$0P:(DE-HGF)0$$aFulco, Umberto Laino$$b5
001022187 7001_ $$0P:(DE-HGF)0$$aAvilla, Clarita Maria Secco$$b6
001022187 7001_ $$0P:(DE-Juel1)179561$$aEberle, Raphael Josef$$b7$$ufzj
001022187 7001_ $$0P:(DE-HGF)0$$aSantos, Igor de Andrade$$b8
001022187 7001_ $$0P:(DE-Juel1)179345$$aKorostov, Karolina$$b9$$ufzj
001022187 7001_ $$0P:(DE-HGF)0$$aWebber, Mayara Lucia$$b10
001022187 7001_ $$0P:(DE-HGF)0$$ada Silva, Gislaine Celestino Dutra$$b11
001022187 7001_ $$0P:(DE-HGF)0$$aNogueira, Maurício Lacerda$$b12
001022187 7001_ $$0P:(DE-HGF)0$$aJardim, Ana Carolina Gomes$$b13
001022187 7001_ $$0P:(DE-HGF)0$$aRegasin, Luis Octavio$$b14
001022187 7001_ $$0P:(DE-Juel1)180738$$aCoronado, Mônika Aparecida$$b15$$eCorresponding author$$ufzj
001022187 7001_ $$0P:(DE-HGF)0$$aPacca, Carolina Colombelli$$b16$$eCorresponding author
001022187 773__ $$0PERI:(DE-600)3035226-5$$a10.1016/j.crmicr.2023.100217$$gVol. 6, p. 100217 -$$p100217 -$$tCurrent research in microbial sciences$$v6$$x2666-5174$$y2024
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