ArticleAntiviral research2021
Dual inhibition of SARS-CoV-2 and human rhinovirus with protease inhibitors in clinical development.
Article in Antiviral research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 56 citations in OpenAlex.
- Structural insights into the antiviral efficacy of AG7404 against human rhinovirus 3C proteases.IUCrJ · 2026Article
- Peptidomimetic Phenoxymethyl Ketone Warheads as Potent Dual-Mode Inhibitors against SARS-CoV-2 MJournal of medicinal chemistry · 2025Article
- EV-D68 cleaves LARP1 and PABPC1 by 3Cpro to redirect host mRNA translation machinery toward its genomic RNA.PLoS pathogens · 2025Article
- Molecular Dynamics Simulation of SARS-CoV-2 E Ion Channel: The Study of Lone Protein and its Conformational Changes in Complex with Potential Cage Inhibitors.Current computer-aided drug design · 2025Article
- DMSO might impact ligand binding, capsid stability, and RNA interaction in viral preparations.Scientific reports · 2024Article
- 3-chymotrypsin-like protease in SARS-CoV-2.Bioscience reports · 2024Review
- Breaking the Chain: Protease Inhibitors as Game Changers in Respiratory Viruses Management.International journal of molecular sciences · 2024Review
- Review
- Development of Fluorescence-Based Assays for Key Viral Proteins in the SARS-CoV-2 Infection Process and Lifecycle.International journal of molecular sciences · 2024Review
- On the origins of SARS-CoV-2 main protease inhibitors.RSC medicinal chemistry · 2024Review
- The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease InhibitormBio · 2023Article
- Discovery of All-d-Peptide Inhibitors of SARS-CoV-2 3C-like Protease.ACS chemical biology · 2023Article
- Structure-based lead optimization of peptide-based vinyl methyl ketones as SARS-CoV-2 main protease inhibitors.European journal of medicinal chemistry · 2023Article
- Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro.Frontiers in pharmacology · 2023Article
- Structure and inhibition of SARS-CoV-1 and SARS-CoV-2 main proteases by oral antiviral compound AG7404.Antiviral research · 2022Article
- Review of Developments in Combating COVID-19 by Vaccines, Inhibitors, Radiations, and Nonthermal Plasma.Current issues in molecular biology · 2022Review
- Allosteric inhibitors of the main protease of SARS-CoV-2.Antiviral research · 2022Article
- A Warhead Substitution Study on the Coronavirus Main Protease Inhibitor Nirmatrelvir.ACS medicinal chemistry letters · 2022Article
- Penicillin Derivatives Inhibit the SARS-CoV-2 Main Protease by Reaction with Its Nucleophilic Cysteine.Journal of medicinal chemistry · 2022Article
- [Nirmatrelvir plus ritonavir (Paxlovid) a potent SARS-CoV-2 3CLpro protease inhibitor combination].Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2022Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 3-chymotrypsin-like cysteine protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered a major target for the discovery of direct antiviral agents. We previously reported the evaluation of SARS-CoV-2 3CLpro inhibitors in a novel self-assembled monolayer desorption ionization mass spectrometry (SAMDI-MS) enzymatic assay (Gurard-Levin et al., 2020). The assay was further improved by adding the rhinovirus HRV3C protease to the same well as the SARS-CoV-2 3CLpro enzyme. High substrate specificity for each enzyme allowed the proteases to be combined in a single assay reaction without interfering with their individual activities. This novel duplex assay was used to profile a diverse set of reference protease inhibitors. The protease inhibitors were grouped into three categories based on their relative potency against 3CLpro and HRV3C including those that are: equipotent against 3CLpro and HRV3C (GC376 and calpain inhibitor II), selective for 3CLpro (PF-00835231, calpain inhibitor XII, boceprevir), and selective for HRV3C (rupintrivir). Structural analysis showed that the combination of minimal interactions, conformational flexibility, and limited bulk allows GC376 and calpain inhibitor II to potently inhibit both enzymes. In contrast, bulkier compounds interacting more tightly with pockets P2, P3, and P4 due to optimization for a specific target display a more selective inhibition profile. Consistently, the most selective viral protease inhibitors were relatively weak inhibitors of human cathepsin L. Taken together, these results can guide the design of cysteine protease inhibitors that are either virus-specific or retain a broad antiviral spectrum against coronaviruses and rhinoviruses.
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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.