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Disruption of disulfides within RBD of SARS-CoV-2 spike protein prevents fusion and represents a target for viral entry inhibition by registered drugs.
Mancek-Keber, Mateja; Hafner-Bratkovic, Iva; Lainscek, Dusko; Bencina, Mojca; Govednik, Tea; Orehek, Sara; Plaper, Tjasa; Jazbec, Vid; Bergant, Valter; Grass, Vincent; Pichlmair, Andreas; Jerala, Roman.
Afiliación
  • Mancek-Keber M; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
  • Hafner-Bratkovic I; Centre of Excellence EN-FIST, Ljubljana, Slovenia.
  • Lainscek D; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
  • Bencina M; Centre of Excellence EN-FIST, Ljubljana, Slovenia.
  • Govednik T; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
  • Orehek S; Centre of Excellence EN-FIST, Ljubljana, Slovenia.
  • Plaper T; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
  • Jazbec V; Centre of Excellence EN-FIST, Ljubljana, Slovenia.
  • Bergant V; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
  • Grass V; Graduate School of Biomedicine, University of Ljubljana, Ljubljana, Slovenia.
  • Pichlmair A; Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
  • Jerala R; Graduate School of Biomedicine, University of Ljubljana, Ljubljana, Slovenia.
FASEB J ; 35(6): e21651, 2021 06.
Article en En | MEDLINE | ID: mdl-34004056
The SARS-CoV-2 pandemic imposed a large burden on health and society. Therapeutics targeting different components and processes of the viral infection replication cycle are being investigated, particularly to repurpose already approved drugs. Spike protein is an important target for both vaccines and therapeutics. Insights into the mechanisms of spike-ACE2 binding and cell fusion could support the identification of compounds with inhibitory effects. Here, we demonstrate that the integrity of disulfide bonds within the receptor-binding domain (RBD) plays an important role in the membrane fusion process although their disruption does not prevent binding of spike protein to ACE2. Several reducing agents and thiol-reactive compounds are able to inhibit viral entry. N-acetyl cysteine amide, L-ascorbic acid, JTT-705, and auranofin prevented syncytia formation, viral entry into cells, and infection in a mouse model, supporting disulfides of the RBD as a therapeutically relevant target.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetilcisteína / Ácido Ascórbico / Compuestos de Sulfhidrilo / Auranofina / Disulfuros / Ésteres / Internalización del Virus / Glicoproteína de la Espiga del Coronavirus / Amidas / SARS-CoV-2 Límite: Humans Idioma: En Revista: FASEB J Asunto de la revista: BIOLOGIA / FISIOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Eslovenia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetilcisteína / Ácido Ascórbico / Compuestos de Sulfhidrilo / Auranofina / Disulfuros / Ésteres / Internalización del Virus / Glicoproteína de la Espiga del Coronavirus / Amidas / SARS-CoV-2 Límite: Humans Idioma: En Revista: FASEB J Asunto de la revista: BIOLOGIA / FISIOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Eslovenia Pais de publicación: Estados Unidos