Evidence map›Paper›PMID 36604514›Full record

ArticleNature microbiology2023

Fluorogenic reporter enables identification of compounds that inhibit SARS-CoV-2.

Junjiao Yang, Yinghong Xiao, Peter V Lidsky, Chien-Ting Wu, Luke R Bonser, Shiming Peng, Miguel A Garcia-Knight, Michel Tassetto, Chan-I Chung, Xiaoquan Li and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature microbiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Protein Engineering for Spatiotemporally Resolved Cellular Monitoring.Annual review of analytical chemistry (Palo Alto, Calif.) · 2025
    Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. COVID-19 and Diarylamidines: The Parasitic Connection.International journal of molecular sciences · 2023
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 3 institutions in 1 country.

Junjiao Yang *Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0003-4844-2492
Yinghong Xiao *Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-6850-6521
Peter V Lidsky *Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
Chien-Ting WuDepartment of Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University, Stanford, CA, USA.
Luke R BonserLung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-9942-5567
Shiming PengDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-5830-243X
Miguel A Garcia-KnightDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
Michel TassettoDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-5666-8796
Chan-I ChungDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Xiaoquan LiDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Tsuguhisa NakayamaDepartment of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA, USA.ORCID 0000-0001-8761-9292
Ivan T LeeDivision of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Jayakar V NayakDepartment of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA, USA.ORCID 0000-0003-4454-0861
Khadija GhiasLung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Kirsten L HargettLung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Brian K ShoichetDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
David J ErleLung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-2171-0648
Peter K JacksonDepartment of Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-1742-2539
Raul AndinoDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. raul.andino@ucsf.edu.ORCID 0000-0001-5503-9349
Xiaokun ShuDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA. xiaokun.shu@ucsf.edu.ORCID 0000-0001-9248-7095
University of California, San Francisco · USStanford University · USVA Palo Alto Health Care System · US

Funding

Understanding Asthma EndotypesU19AI077439 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI David J Erle · 2008 to 2026
$41.1M
Unbiased Functional Characterization of Enterovirus-Host InteractionsP01AI091575 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDINO, RAUL · 2011 to 2015
$10.5M
Airway epithelial cell gene regulation: new mechanisms and therapeutic strategiesR35HL145235 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ERLE, DAVID J · 2019 to 2025
$6.8M
RNA PROTEIN INTERACTIONS IN POLIOVIRUS REPLICATIONR01AI040085 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDINO, RAUL · 1998 to 2019
$5.8M
EQUIPMENT for Designing a new class of fluorescent reporters for imaging dynamic cell signaling in live animalsR35GM131766 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHU, XIAOKUN · 2019 to 2025
$4.0M
RECOMBINANT PICORNAVIRUSES AS AIDS VACCINESR01AI036178 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDINO, RAUL · 1994 to 2011
$3.6M
RNA PROTEIN INTERACTIONS IN POLIOVIRUS REPLICATIONR21AI040085 · NIAID · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI ANDINO, RAUL · 1996 to 1996
–
NHLBI NIH HHS R35 HL145235NIAID NIH HHS N01 AI040085NIAID NIH HHS P01 AI091575NIAID NIH HHS R01 AI036178NIAID NIH HHS R01 AI040085NIAID NIH HHS U19 AI077439NIGMS NIH HHS R35 GM131766
6 · The paper itself

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.

Indexed as

COVID-19SARS-CoV-2Angiotensin-Converting Enzyme 2AnimalsAntiviral AgentsChlorocebus aethiopsHumansMicePeptidyl-Dipeptidase AQuassinsVero CellsAngiotensin-Converting Enzyme 2Antiviral Agentsbruceine APeptidyl-Dipeptidase AQuassins

Identifiers

PMID36604514
PMCPMC9831272
OpenAlexW4313557302

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.