Rational Design of Capsid Protein VP1 Degraders to Overcome Pleconaril Resistance in Inhibiting Enterovirus D68.

Kan Li, Jiabin Ni, Guangjin Fan, Jun Wang

Abstract read

In one paragraph

Article in JACS Au, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing 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

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3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Kan LiDepartment of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.

Jiabin NiDepartment of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.

Guangjin FanDepartment of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.

Jun WangDepartment of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.ORCID https://orcid.org/0000-0002-4845-4621

Funding

Development of 2C inhibitors as broad-spectrum enterovirus antiviralsR01AI179926 · NIAID · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI Jun Wang · 2024 to 2026

$2.3M

NIAID NIH HHS R01 AI179926

6 · The paper itself

Abstract

Enterovirus D68 (EV-D68) is an emerging respiratory pathogen with pandemic potential, yet no vaccines or antivirals are available. Capsid inhibitors, such as pleconaril, that target the hydrophobic canyon on the viral capsid protein VP1, exhibit potent antiviral activity but have a low barrier to resistance. Here, we report a targeted protein degradation strategy to overcome antiviral resistance by selectively degrading the capsid protein VP1. Through a structure-based rational design, we developed a series of pleconaril-based PROTACs that recruit the cereblon (CRBN) E3 ligase to degrade the capsid VP1 protein. We established a single-cycle replication assay integrating immunofluorescence and Western blot to quantify VP1 protein levels when compounds were added postviral entry. Linker and CRBN ligand optimization led to the identification of

Indexed as

antiviralcapsid proteinenterovirusEV-D68PROTAC

Identifiers

PMID42063851

DOI10.1021/jacsau.6c00039

PMCPMC13126190

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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.