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Fluorogenic reporter enables identification of compounds that inhibit SARS-CoV-2.
Yang, Junjiao; Xiao, Yinghong; Lidsky, Peter V; Wu, Chien-Ting; Bonser, Luke R; Peng, Shiming; Garcia-Knight, Miguel A; Tassetto, Michel; Chung, Chan-I; Li, Xiaoquan; Nakayama, Tsuguhisa; Lee, Ivan T; Nayak, Jayakar V; Ghias, Khadija; Hargett, Kirsten L; Shoichet, Brian K; Erle, David J; Jackson, Peter K; Andino, Raul; Shu, Xiaokun.
Afiliación
  • Yang J; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
  • Xiao Y; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
  • Lidsky PV; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Wu CT; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Bonser LR; Department of Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University, Stanford, CA, USA.
  • Peng S; Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Garcia-Knight MA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
  • Tassetto M; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Chung CI; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Li X; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
  • Nakayama T; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
  • Lee IT; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
  • Nayak JV; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
  • Ghias K; Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA, USA.
  • Hargett KL; Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Shoichet BK; Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA, USA.
  • Erle DJ; Department of Otolaryngology-Head and Neck Surgery, VA Palo Alto Health Care System, Palo Alto, CA, USA.
  • Jackson PK; Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Andino R; Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Shu X; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Nat Microbiol ; 8(1): 121-134, 2023 01.
Article en En | MEDLINE | ID: mdl-36604514
ABSTRACT
The coronavirus SARS-CoV-2 causes the severe disease COVID-19. SARS-CoV-2 infection is initiated by interaction of the viral spike protein and host receptor angiotensin-converting enzyme 2 (ACE2). We report an improved bright and reversible fluorogenic reporter, named SURF (split UnaG-based reversible and fluorogenic protein-protein interaction reporter), that we apply to monitor real-time interactions between spike and ACE2 in living cells. SURF has a large dynamic range with a dark-to-bright fluorescence signal that requires no exogenous cofactors. Utilizing this reporter, we carried out a high-throughput screening of small-molecule libraries. We identified three natural compounds that block replication of SARS-CoV-2 in both Vero cells and human primary nasal and bronchial epithelial cells. Cell biological and biochemical experiments validated all three compounds and showed that they block the early stages of viral infection. Two of the inhibitors, bruceine A and gamabufotalin, were also found to block replication of the Delta and Omicron variants of SARS-CoV-2. Both bruceine A and gamabufotalin exhibited potent antiviral activity in K18-hACE2 and wild-type C57BL6/J mice, as evidenced by reduced viral titres in the lung and brain, and protection from alveolar and peribronchial inflammation in the lung, thereby limiting disease progression. We propose that our fluorescent assay can be applied to identify antiviral compounds with potential as therapeutic treatment for COVID-19 and other respiratory diseases.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: SARS-CoV-2 / COVID-19 Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Microbiol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: SARS-CoV-2 / COVID-19 Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Microbiol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos