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Unveiling tetrahydroquinolines as promising BVDV entry inhibitors: Targeting the envelope protein.
Leal, Emilse S; Pascual, María J; Adler, Natalia S; Arrupe, Nicolás; Merwaiss, Fernando; Giordano, Luciana; Fidalgo, Daniela; Álvarez, Diego; Bollini, Mariela.
Afiliação
  • Leal ES; Centro de Investigaciones en Bionanociencias (CIBION)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
  • Pascual MJ; Instituto de Investigaciones Biotecnológicas, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de San Martín, Argentina.
  • Adler NS; Centro de Investigaciones en Bionanociencias (CIBION)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
  • Arrupe N; Centro de Investigaciones en Bionanociencias (CIBION)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
  • Merwaiss F; Instituto de Investigaciones Biotecnológicas, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de San Martín, Argentina.
  • Giordano L; Centro de Investigaciones en Bionanociencias (CIBION)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
  • Fidalgo D; Centro de Investigaciones en Bionanociencias (CIBION)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
  • Álvarez D; Instituto de Investigaciones Biotecnológicas, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de San Martín, Argentina. Electronic address: dalvarez@iib.unsam.edu.ar.
  • Bollini M; Centro de Investigaciones en Bionanociencias (CIBION)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Electronic address: mariela.bollini@cibion.conicet.gov.ar.
Virology ; 590: 109968, 2024 02.
Article em En | MEDLINE | ID: mdl-38141499
ABSTRACT
Bovine viral diarrhea virus (BVDV) is known to cause financial losses and decreased productivity in the cattle industry worldwide. Currently, there are no available antiviral treatments for effectively controlling BVDV infections in laboratories or farms. The BVDV envelope protein (E2) mediates receptor recognition on the cell surface and is required for fusion of virus and cell membranes after the endocytic uptake of the virus during the entry process. Therefore, E2 is an attractive target for the development of antiviral strategies. To identify BVDV antivirals targeting E2 function, we defined a binding site in silico located in domain IIIc at the interface between monomers in the disulfide linked dimer of E2. Employing a de novo design methodology to identify compounds with the potential to inhibit the E2 function, compound 9 emerged as a promising candidate with remarkable antiviral activity and minimal toxicity. In line with targeting of E2 function, compound 9 was found to block the virus entry into host cells. Furthermore, we demonstrated that compound 9 selectively binds to recombinant E2 in vitro. Molecular dynamics simulations (MD) allowed describing a possible interaction pattern between compound 9 and E2 and indicated that the S enantiomer of compound 9 may be responsible for the antiviral activity. Future research endeavors will focus on synthesizing enantiomerically pure compounds to further support these findings. These results highlight the usefulness of de novo design strategies to identify a novel class of BVDV inhibitors that block E2 function inhibiting virus entry into the host cell.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus da Diarreia Viral Bovina / Vírus da Diarreia Viral Bovina Tipo 1 Limite: Animals Idioma: En Revista: Virology Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus da Diarreia Viral Bovina / Vírus da Diarreia Viral Bovina Tipo 1 Limite: Animals Idioma: En Revista: Virology Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos