Evidence map›Paper›PMID 34917260›Full record

ArticleACS medicinal chemistry letters2021

Nanoparticular Inhibitors of Flavivirus Proteases from Zika, West Nile and Dengue Virus Are Cell-Permeable Antivirals.

Barbara Schroeder, Peter Demirel, Christina Fischer, Enaam Masri, Stephanie Kallis, Lisa Redl, Thomas Rudolf, Silke Bergemann, Christoph Arkona, Christoph Nitsche and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS medicinal chemistry letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.8field-weighted citation impact, top 25% 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

1 citing paper in PubMed, 7 citations in OpenAlex.

  1. Review
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

12 authors at 3 institutions in 2 countries.

Barbara SchroederPharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2 + 4, 14195 Berlin, Germany.
Peter DemirelPharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2 + 4, 14195 Berlin, Germany.
Christina FischerPharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2 + 4, 14195 Berlin, Germany.
Enaam MasriPharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2 + 4, 14195 Berlin, Germany.
Stephanie KallisDepartment for Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, 69120 Heidelberg, Germany.
Lisa RedlPharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2 + 4, 14195 Berlin, Germany.
Thomas RudolfPharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2 + 4, 14195 Berlin, Germany.
Silke BergemannPharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2 + 4, 14195 Berlin, Germany.
Christoph ArkonaPharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2 + 4, 14195 Berlin, Germany.
Christoph NitscheResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID https://orcid.org/0000-0002-3704-2699
Ralf BartenschlagerDepartment for Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, 69120 Heidelberg, Germany.
Jörg RademannPharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2 + 4, 14195 Berlin, Germany.ORCID https://orcid.org/0000-0001-6678-3165
Freie Universität Berlin · DEHeidelberg University · DEAustralian National University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Viral proteases have been established as drug targets in several viral diseases including human immunodeficiency virus and hepatitis C virus infections due to the essential role of these enzymes in virus replication. In contrast, no antiviral therapy is available to date against flaviviral infections including those by Zika virus (ZIKV), West Nile virus (WNV), or dengue virus (DENV). Numerous potent inhibitors of flaviviral proteases have been reported; however, a huge gap remains between the in vitro and intracellular activities, possibly due to low cellular uptake of the charged compounds. Here, we present an alternative, nanoparticular approach to antivirals. Conjugation of peptidomimetic inhibitors and cell-penetrating peptides to dextran yielded chemically defined nanoparticles that were potent inhibitors of flaviviral proteases. Peptide-dextran conjugates inhibited viral replication and infection in cells at nontoxic, low micromolar or even nanomolar concentrations. Thus, nanoparticular antivirals might be alternative starting points for the development of broad-spectrum antiflaviviral drugs.

Identifiers

PMID34917260
PMCPMC8667303
OpenAlexW3215202261

What Socratic 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 Socratic graph.