Evidence map›Paper›PMID 33619959›Full record

ArticleACS chemical biology2021

Inhibiting HTLV-1 Protease: A Viable Antiviral Target.

Gordon J Lockbaum, Mina Henes, Nathaniel Talledge, Linah N Rusere, Klajdi Kosovrasti, Ellen A Nalivaika, Mohan Somasundaran, Akbar Ali, Louis M Mansky, Nese Kurt Yilmaz and 1 more

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

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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

11 authors at 2 institutions in 1 country.

Gordon J LockbaumDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.ORCID 0000-0003-2720-6984
Mina HenesDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.
Nathaniel TalledgeInstitute for Molecular Virology, Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, Minnesota 55455, United States.ORCID 0000-0002-4603-0120
Linah N RusereDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.
Klajdi KosovrastiDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.
Ellen A NalivaikaDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.
Mohan SomasundaranDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.
Akbar AliDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.ORCID 0000-0003-3491-791X
Louis M ManskyInstitute for Molecular Virology, Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, Minnesota 55455, United States.
Nese Kurt YilmazDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.ORCID 0000-0002-5036-676X
Celia A SchifferDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.ORCID 0000-0003-2270-6613
University of Massachusetts Chan Medical School · USUniversity of Minnesota · US

Funding

Training in PharmacoNeuroImmune Substance Abuse ResearchT32DA007097 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MOLITOR, THOMAS WILLIAM · 1985 to 2021
$13.1M
Tracking the evolution of drug resistance for highly potent HIV protease inhibitoP01GM109767 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SHERMAN, BRIAN WOODY · 2014 to 2018
$8.0M
HTLV-1 Particle Analysis and Gag InteractionsR01GM098550 · NIGMS · UNIVERSITY OF MINNESOTA · PI MANSKY, LOUIS M. · 2012 to 2020
$3.1M
High-Speed High-Sensitivity Detector for X-ray Micro-Crystallography at GM/CA@APSS10OD012289 · OD · UNIVERSITY OF CHICAGO · PI FISCHETTI, ROBERT F. · 2014 to 2014
$2.0M
Design of Protease Inhibitors to Target HTLV-1R21AI149716 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SCHIFFER, CELIA A. · 2020 to 2021
$461k
Molecular Determinants of Retroviral Capsid Morphology using a Novel Imaging ApproachF32AI150351 · NIAID · UNIVERSITY OF MINNESOTA · PI TALLEDGE, NATHANIEL LEE · 2020 to 2021
$141k
NIAID NIH HHS F32 AI150351NIAID NIH HHS R21 AI149716NIDA NIH HHS T32 DA007097NIGMS NIH HHS P01 GM109767NIGMS NIH HHS R01 GM098550NIH HHS S10 OD012289
6 · The paper itself

Abstract

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that can cause severe paralytic neurologic disease and immune disorders as well as cancer. An estimated 20 million people worldwide are infected with HTLV-1, with prevalence reaching 30% in some parts of the world. In stark contrast to HIV-1, no direct acting antivirals (DAAs) exist against HTLV-1. The aspartyl protease of HTLV-1 is a dimer similar to that of HIV-1 and processes the viral polyprotein to permit viral maturation. We report that the FDA-approved HIV-1 protease inhibitor darunavir (DRV) inhibits the enzyme with 0.8 μM potency and provides a scaffold for drug design against HTLV-1. Analogs of DRV that we designed and synthesized achieved submicromolar inhibition against HTLV-1 protease and inhibited Gag processing in viral maturation assays and in a chronically HTLV-1 infected cell line. Cocrystal structures of these inhibitors with HTLV-1 protease highlight opportunities for future inhibitor design. Our results show promise toward developing highly potent HTLV-1 protease inhibitors as therapeutic agents against HTLV-1 infections.

Indexed as

Amino Acid SequenceAntiviral AgentsAspartic Acid EndopeptidasesDarunavirDrug DiscoveryEscherichia coliHumansHuman T-lymphotropic virus 1Molecular Dynamics SimulationMolecular StructureMolecular Targeted TherapyProtease InhibitorsProtein BindingProtein ConformationStructure-Activity RelationshipAntiviral AgentsAspartic Acid EndopeptidasesDarunavirHTLV-1 proteaseProtease Inhibitors

Identifiers

PMID33619959
PMCPMC8126997
OpenAlexW3132715547

What OpenQuestion holds

Textmetadata
LicenceTDM
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.