Evidence map›Paper›PMID 15673742›Full record

ArticleAntimicrobial agents and chemotherapy2005

Conservation of amino acids in human rhinovirus 3C protease correlates with broad-spectrum antiviral activity of rupintrivir, a novel human rhinovirus 3C protease inhibitor.

S L Binford, F Maldonado, M A Brothers, P T Weady, L S Zalman, J W Meador, D A Matthews, A K Patick

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

79 citing papers in PubMed, 156 citations in OpenAlex.

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  8. Human Assembloid Model of Emergent Neurotropic Enteroviruses.bioRxiv : the preprint server for biology · 2025
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  19. PRSC chemical biology · 2023
    Review
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19 more citing papers are in PubMed but not listed here.

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

8 authors at 1 institution in 1 country.

S L BinfordDepartment of Virology, Pfizer Global Research and Development, 10777 Science Center Dr., San Diego, CA 92121, USA.
F Maldonado
M A Brothers
P T Weady
L S Zalman
J W Meador
D A Matthews
A K Patick
Pfizer (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The picornavirus 3C protease is required for the majority of proteolytic cleavages that occur during the viral life cycle. Comparisons of published amino acid sequences from 6 human rhinoviruses (HRV) and 20 human enteroviruses (HEV) show considerable variability in the 3C protease-coding region but strict conservation of the catalytic triad residues. Rupintrivir (formerly AG7088) is an irreversible inhibitor of HRV 3C protease with potent in vitro activity against all HRV serotypes (48 of 48), HEV strains (4 of 4), and untyped HRV field isolates (46 of 46) tested. To better understand the relationship between in vitro antiviral activity and 3C protease-rupintrivir binding interactions, we performed nucleotide sequence analyses on an additional 21 HRV serotypes and 11 HRV clinical isolates. Antiviral activity was also determined for 23 HRV clinical isolates and four additional HEV strains. Sequence comparison of 3C proteases (n = 58) show that 13 and 11 of the 14 amino acids that are involved in side chain interactions with rupintrivir are strictly conserved among HRV and HEV, respectively. These sequence analyses are consistent with the comparable in vitro antiviral potencies of rupintrivir against all HRV serotypes, HRV isolates, and HEV strains tested (50% effective concentration range, 3 to 183 nM; n = 125). In summary, the conservation of critical amino acid residues in 3C protease and the observation of potent, broad-spectrum antipicornavirus activity of rupintrivir highlight the advantages of 3C protease as an antiviral target.

Indexed as

3C Viral ProteasesAmino AcidsAntiviral AgentsConserved SequenceCysteine EndopeptidasesHeLa CellsHumansIsoxazolesMolecular Sequence DataPhenylalanineProtease InhibitorsPyrrolidinonesReverse Transcriptase Polymerase Chain ReactionRhinovirusRNA, ViralValine3C Viral ProteasesAmino AcidsAntiviral AgentsCysteine EndopeptidasesIsoxazolesPhenylalanineProtease InhibitorsPyrrolidinonesRNA, ViralrupintrivirValineViral Proteins

Identifiers

PMID15673742
PMCPMC547258
OpenAlexW2106051437

What OpenQuestion holds

Textmetadata
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.