ArticleViruses2023
In Silico Screening of Inhibitors of the Venezuelan Equine Encephalitis Virus Nonstructural Protein 2 Cysteine Protease.
Article in Viruses, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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.
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.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Chikungunya virus nsP2: Insights into viral replication, pathogenesis, and therapeutic targeting.Virulence · 2026Review
- Computational identification of potential inhibitors for chikungunya virus nsP2pro.Royal Society open science · 2026Article
- Western equine encephalitis virus: A comprehensive review of epidemics, transmission, hosts, and strategies for mitigation.Virulence · 2025Review
- Article
- Alphavirus nsP2: A Multifunctional Regulator of Viral Replication and Promising Target for Anti-Alphavirus Therapies.Reviews in medical virology · 2025Review
- Identification of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Heterologous expression, purification, and biochemical characterization of protease 3075 from Cohnella sp. A01.PloS one · 2024Article
- Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs.Molecules (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Venezuelan equine encephalitis virus (VEEV) nonstructural protein 2 (nsP2) cysteine protease (EC 3.4.22.B79) is essential for viral replication. High throughput in silico/in vitro screening using a focused set of known cysteine protease inhibitors identified two epoxysuccinyl prodrugs, E64d and CA074 methyl ester (CA074me) and a reversible oxindole inhibitor. Here, we determined the X-ray crystal structure of the CA074-inhibited nsP2 protease and compared it with our E64d-inhibited structure. We found that the two inhibitors occupy different locations in the protease. We designed hybrid inhibitors with improved potency. Virus yield reduction assays confirmed that the viral titer was reduced by >5 logs with CA074me. Cell-based assays showed reductions in viral replication for CHIKV, VEEV, and WEEV, and weaker inhibition of EEEV by the hybrid inhibitors. The most potent was NCGC00488909-01 which had an EC
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Registered trials
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.