Drug repurposing screens identify Tubercidin as a potent antiviral agent against porcine nidovirus infections.
Virus Res
; 339: 199275, 2024 01 02.
Article
en En
| MEDLINE
| ID: mdl-38008220
ABSTRACT
The emergence of new coronaviruses poses a significant threat to animal husbandry and human health. Porcine epidemic diarrhea virus (PEDV) is considered a re-emerging porcine enteric coronavirus, which causes fatal watery diarrhea in piglets. Currently, there are no effective drugs to combat PEDV. Drug repurposing screens have emerged as an attractive strategy to accelerate antiviral drug discovery and development. Here, we screened 206 natural products for antiviral activity using live PEDV infection in Vero cells and identified ten candidate antiviral agents. Among them, Tubercidin, a nucleoside analog derived from Streptomyces tubercidicus, showed promising antiviral activity against PEDV infection. Furthermore, we demonstrated that Tubercidin exhibited significant antiviral activity against both classical and variant PEDV. Time of addition assay showed that Tubercidin displayed a significant inhibitory effect on viral post-entry events but not during other periods. Molecular docking analysis indicated that Tubercidin had better docking efficiency and formed hydrophobic interactions with the active pocket of RNA-dependent RNA polymerase (RdRp) of PEDV and other nidoviruses. Additionally, Tubercidin can effectively suppress other porcine nidoviruses, such as SADS-CoV and PRRSV, demonstrating its broad-spectrum antiviral properties. In summary, our findings provide valuable evidence for the antiviral activity of Tubercidin and offer insights into the development of new strategies for the prevention and treatment of coronavirus infections.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades de los Porcinos
/
Infecciones por Coronavirus
/
Coronavirus
/
Nidovirales
/
Virus de la Diarrea Epidémica Porcina
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Virus Res
Asunto de la revista:
VIROLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos