Evidence map›Paper›PMID 34811361›Full record

ArticleNature communications2021

Design of modular autoproteolytic gene switches responsive to anti-coronavirus drug candidates.

Nik Franko, Ana Palma Teixeira, Shuai Xue, Ghislaine Charpin-El Hamri, Martin Fussenegger

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

16 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. A programmable genetic platform for engineering noninvasive biosensors.bioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Synthetic Gene Circuits for Regulation of Next-Generation Cell-Based Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  10. Article
  11. Article
  12. Article
  13. Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022
    Review
  14. Review
  15. Article
  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Nik FrankoETH Zurich, Department of Biosystems Science and Engineering, Mattenstrasse 26, CH-4058, Basel, Switzerland.
Ana Palma TeixeiraETH Zurich, Department of Biosystems Science and Engineering, Mattenstrasse 26, CH-4058, Basel, Switzerland.
Shuai XueETH Zurich, Department of Biosystems Science and Engineering, Mattenstrasse 26, CH-4058, Basel, Switzerland.
Ghislaine Charpin-El HamriDépartement Génie Biologique, Institut Universitaire de Technologie, Université Claude Bernard Lyon 1, F-69622, Villeurbanne, Cedex, France.
Martin FusseneggerETH Zurich, Department of Biosystems Science and Engineering, Mattenstrasse 26, CH-4058, Basel, Switzerland. fussenegger@bsse.ethz.ch.ORCID 0000-0001-8545-667X
ETH Zurich · CHUniversité Claude Bernard Lyon 1 · FRUniversity of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The main (Mpro) and papain-like (PLpro) proteases encoded by SARS-CoV-2 are essential to process viral polyproteins into functional units, thus representing key targets for anti-viral drug development. There is a need for an efficient inhibitor screening system that can identify drug candidates in a cellular context. Here we describe modular, tunable autoproteolytic gene switches (TAGS) relying on synthetic transcription factors that self-inactivate, unless in the presence of coronavirus protease inhibitors, consequently activating transgene expression. TAGS rapidly report the impact of drug candidates on Mpro and PLpro activities with a high signal-to-noise response and a sensitivity matching concentration ranges inhibiting viral replication. The modularity of the TAGS enabled the study of other Coronaviridae proteases, characterization of mutations and multiplexing of gene switches in human cells. Mice implanted with Mpro or PLpro TAGS-engineered cells enabled analysis of the activity and bioavailability of protease inhibitors in vivo in a virus-free setting.

Indexed as

AnimalsAntiviral AgentsCOVID-19 Drug TreatmentMiceSARS-CoV-2Virus ReplicationAntiviral Agents

Identifiers

PMID34811361
PMCPMC8609006
OpenAlexW3214964141

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.