| Full text | |
| Author(s): Show less - |
Coimbra, Lais D.
;
Shimizu, Jacqueline F.
;
Nagai, Alice
;
Borin, Alexandre
;
Fontoura, Marina A.
;
Concha, Juan O.
;
Leme, Luiza
;
do Carmo, Ketleen Lucas
;
de Oliveira, Leonardo C.
;
Soprano, Adriana S.
;
Felipe, Jaqueline S.
;
Silva, Amanda B.
;
Forato, Julia
;
Scachetti, Gabriel C.
;
Crump, Colin M.
;
Sacchetto, Livia
;
Nogueira, Mauricio L.
;
Bezerra, Eduardo H. S.
;
Guimaraes, Samuel L.
;
Cordeiro, Artur T.
;
Proenca-Modena, Jose Luiz
;
Dasilva, Luis L. P.
;
Boratto, Paulo V. M.
;
Hanchuk, Talita D. Melo
;
Marques, Rafael Elias
Total Authors: 25
|
| Document type: | Journal article |
| Source: | Antiviral Research; v. 238, p. 12-pg., 2025-04-24. |
| Abstract | |
Oropouche virus (OROV) has caused a new outbreak, with thousands of cases of febrile disease in South and Central America, including regions where the virus was not detected before. Oropouche fever is a neglected mosquito-borne disease that still lacks options for antiviral treatment. We developed a high-throughput screening phenotypic assay using human hepatocyte-derived HuH-7.0 cells to screen over 7700 compounds against OROV infection. We identified 13 hit compounds that were protective against OROV-induced cytopathic effect in cell culture, of which 3 were confirmed: lysergol, amiloride hydrochloride, and pyridostatin TFA, with EC50 values below 2 mu M. Orthogonal assays indicate that both lysergol and pyridostatin present antiviral activity against OROV in HuH-7.0 and T24 cell lines, but lysergol is far more potent, causing up to a 100,000-fold reduction in viral load in the low micromolar range. Mechanistic studies indicate that the antiviral effect of lysergol affects early stages of viral replication, and that lysergol is also active against a recently isolated OROV strain. In conclusion, our phenotypical screening campaign led to the identification of a first-in-class compound with potent antiviral activity against the emerging OROV in cell culture. We conclude that high-throughput screening assays can be implemented in response to the emergence of arboviruses and accelerate the discovery of candidate treatments. (AU) | |
| FAPESP's process: | 22/01379-2 - The role of gut microbiota in susceptibility to experimental infection with St. Louis encephalitis virus (SLEV) |
| Grantee: | Jaqueline de Souza Felipe |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 21/05519-0 - Understanding the role of neutrophil recruitment and activation in arboviral diseases |
| Grantee: | Rafael Elias Marques Pereira Silva |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 22/02278-5 - SELECTION OF COMPOUNDS THROUGH DRUG REPURPOSING AND CHARACTERIZATION OF ANTIVIRAL ACTIVITY AGAINST OROPOUCHE ORTHOBUNYAVIRUS |
| Grantee: | Alexandre Borin Pereira |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 19/02418-9 - Molecular mechanisms of Oropouche Virus assembly |
| Grantee: | Luis Lamberti Pinto da Silva |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 23/16611-0 - Study of immune innate cell migration in a zebrafish model infected with Orthobunyavirus oropoucheense |
| Grantee: | Alexandre Borin Pereira |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 23/10771-6 - Functional study of Envelope Protein N-Glycosylation on St. Louis encephalitis virus Infection. |
| Grantee: | Luiza Leme |
| Support Opportunities: | Scholarships in Brazil - Doctorate |