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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

• Tipo de documento: Artigo Científico
• Fonte: CURRENT RESEARCH IN MICROBIAL SCIENCES; v. 6, p. 11-pg., 2023-12-31.

Resumo

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)

• Processo FAPESP: 23/09590-7 - Desenvolvimento de um método diagnóstico para o rocio vírus e uso de novos compostos como inibidores da NS2B-NS3 protease-helicase de flavivirus
• Beneficiário: Marielena Vogel Saivish
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 18/15083-2 - Síntese e avaliação biológica de isobavachalcona (IBC) e análogos como potenciais agentes contra a tuberculose
• Beneficiário: Luis Octávio Regasini
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/12875-5 - Desenvolvimento de método de diagnóstico para o vírus Rocio e utilização de compostos novos como inibidores da NS2B-NS3 protease-helicase de flavivirus
• Beneficiário: Marielena Vogel Saivish
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/21719-3 - Estudo epidemiológico da dengue (sorotipos 1 a 4) em coorte prospectiva de São José do Rio Preto, São Paulo, Brasil, durante 2014 a 2018
• Beneficiário: Maurício Lacerda Nogueira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/13341-1 - Busca de compostos e peptídeos com potencial atividade antiviral contra Arbovírus de importância clínica
• Beneficiário: Carolina Colombelli Pacca
• Modalidade de apoio: Auxílio à Pesquisa - Regular