Evidence map›Paper›PMID 38889796›Full record

ArticleOpen biology2024

A pan-respiratory antiviral chemotype targeting a transient host multi-protein complex.

Maya Michon, Andreas Müller-Schiffmann, Anuradha F Lingappa, Shao Feng Yu, Li Du, Fred Deiter, Sean Broce, Suguna Mallesh, Jackelyn Crabtree, Usha F Lingappa and 47 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Open biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

57 authors.

Maya MichonProsetta Biosciences, San Francisco, CA, USA.
Andreas Müller-SchiffmannInstitute of Neuropathology, Heinrich Heine University, Düsseldorf, 40225 Germany.
Anuradha F LingappaProsetta Biosciences, San Francisco, CA, USA.
Shao Feng YuProsetta Biosciences, San Francisco, CA, USA.
Li DuVitalant Research Institute, San Francisco, CA, 94118-4417 USA.
Fred DeiterVeterans Administration Medical Center, San Francisco, CA, USA.
Sean BroceProsetta Biosciences, San Francisco, CA, USA.
Suguna MalleshProsetta Biosciences, San Francisco, CA, USA.
Jackelyn CrabtreeUniversity of Georgia, Animal Health Research Center, Athens, GA, 28130 USA.
Usha F LingappaProsetta Biosciences, San Francisco, CA, USA.
Amanda MacieikProsetta Biosciences, San Francisco, CA, USA.
Lisa MüllerInstitute of Virology, Heinrich Heine University, Düsseldorf, 40225 Germany.
Philipp Niklas OstermannInstitute of Virology, Heinrich Heine University, Düsseldorf, 40225 Germany.
Marcel AndréeInstitute of Virology, Heinrich Heine University, Düsseldorf, 40225 Germany.
Ortwin AdamsInstitute of Virology, Heinrich Heine University, Düsseldorf, 40225 Germany.
Heiner SchaalInstitute of Virology, Heinrich Heine University, Düsseldorf, 40225 Germany.
Robert J HoganVitalant Research Institute, San Francisco, CA, 94118-4417 USA.
Ralph A TrippVitalant Research Institute, San Francisco, CA, 94118-4417 USA.
Umesh AppaiahProsetta Biosciences, San Francisco, CA, USA.
Sanjeev K AnandSanto Biotech, LLC, Pendleton, IN, USA.
Thomas W CampiSanto Biotech, LLC, Pendleton, IN, USA.
Michael J FordMS Bioworks, Ann Arbor, MI, USA.
Jonathan C ReedOnipro LLC, Kensington, CA, USA.
Jim LinProsetta Biosciences, San Francisco, CA, USA.
Olayemi AkintundeProsetta Biosciences, San Francisco, CA, USA.
Kiel CopelandProsetta Biosciences, San Francisco, CA, USA.
Christine NicholsProsetta Biosciences, San Francisco, CA, USA.
Emma PetrouskiProsetta Biosciences, San Francisco, CA, USA.
Ana R MoreiraProsetta Biosciences, San Francisco, CA, USA.
I-Ting JiangProsetta Biosciences, San Francisco, CA, USA.
Nicholas DeYarmanProsetta Biosciences, San Francisco, CA, USA.
Ian BrownProsetta Biosciences, San Francisco, CA, USA.
Sharon LauProsetta Biosciences, San Francisco, CA, USA.
Ilana SegalProsetta Biosciences, San Francisco, CA, USA.
Danielle GoldsmithProsetta Biosciences, San Francisco, CA, USA.
Shi HongProsetta Biosciences, San Francisco, CA, USA.
Vinod AsundiProsetta Biosciences, San Francisco, CA, USA.
Erica M BriggsProsetta Biosciences, San Francisco, CA, USA.
Ngwe Sin PhyoProsetta Biosciences, San Francisco, CA, USA.
Markus FroehlichProsetta Biosciences, San Francisco, CA, USA.
Bruce OniskoOnipro LLC, Kensington, CA, USA.
Kent MatlackProsetta Biosciences, San Francisco, CA, USA.
Debendranath DeyProsetta Biosciences, San Francisco, CA, USA.
Jaisri R LingappaDepartment of Global Health, University of Washington, Seattle, WA, 98195, USA.
Dharma M PrasadProsetta Biosciences, San Francisco, CA, USA.
Anatoliy KitaygorodskyyProsetta Biosciences, San Francisco, CA, USA.
Dennis SolasProsetta Biosciences, San Francisco, CA, USA.
Homer BousheyUniversity of California, San Francisco, CA, 94143, USA.
John GreenlandVeterans Administration Medical Center, San Francisco, CA, USA.
Satish PillaiVitalant Research Institute, San Francisco, CA, 94118-4417 USA.
Michael K LoViral Special Pathogens Branch, US Centers for Disease Control and Prevention, Atlanta, GA, USA.
Joel M MontgomeryViral Special Pathogens Branch, US Centers for Disease Control and Prevention, Atlanta, GA, USA.
Christina F SpiropoulouViral Special Pathogens Branch, US Centers for Disease Control and Prevention, Atlanta, GA, USA.
Carsten KorthInstitute of Neuropathology, Heinrich Heine University, Düsseldorf, 40225 Germany.
Suganya SelvarajahProsetta Biosciences, San Francisco, CA, USA.
Kumar PaulvannanProsetta Biosciences, San Francisco, CA, USA.
Vishwanath R LingappaProsetta Biosciences, San Francisco, CA, USA.ORCID 0000-0003-0962-6571

Funding

Targeting druggable coronavirus proteinsU19AI171443 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI SUMIT K CHANDA, Arnab Kumar Chatterjee · 2022 to 2026
$101.4M
NIAID NIH HHS U19 AI171443
6 · The paper itself

Abstract

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.

Indexed as

Antiviral Agents14-3-3 ProteinsAnimalsCell LineHost-Pathogen InteractionsHumansMultiprotein Complexes14-3-3 ProteinsAntiviral AgentsMultiprotein Complexesallosteric modulatordrug discoveryhost–viral interfacepan-respiratory antiviral therapeuticsphenotypic screenviral capsid assembly

Identifiers

PMID38889796
PMCPMC11285769

What Socratic 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 Socratic graph.