Evidence map›Paper›PMID 33525505›Full record

ArticleViruses2021

Antiviral Activity of the G-Quadruplex Ligand TMPyP4 against Herpes Simplex Virus-1.

Sara Artusi, Emanuela Ruggiero, Matteo Nadai, Beatrice Tosoni, Rosalba Perrone, Annalisa Ferino, Irene Zanin, Luigi Xodo, Louis Flamand, Sara N Richter

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

28 citing papers in PubMed, 44 citations in OpenAlex.

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  16. Targeting G-quadruplexes to achieve antiviral activity.Bioorganic & medicinal chemistry letters · 2023
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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

10 authors at 3 institutions in 2 countries.

Sara ArtusiDepartment of Molecular Medicine, University of Padua, 35121 Padua, Italy.ORCID 0000-0003-0401-2538
Emanuela RuggieroDepartment of Molecular Medicine, University of Padua, 35121 Padua, Italy.ORCID 0000-0003-0989-4074
Matteo NadaiDepartment of Molecular Medicine, University of Padua, 35121 Padua, Italy.ORCID 0000-0003-3831-4892
Beatrice TosoniDepartment of Molecular Medicine, University of Padua, 35121 Padua, Italy.ORCID 0000-0002-1641-4537
Rosalba PerroneDepartment of Molecular Medicine, University of Padua, 35121 Padua, Italy.ORCID 0000-0001-8894-4548
Annalisa FerinoDepartment of Medicine, University of Udine, 33100 Udine, Italy.
Irene ZaninDepartment of Molecular Medicine, University of Padua, 35121 Padua, Italy.
Luigi XodoDepartment of Medicine, University of Udine, 33100 Udine, Italy.ORCID 0000-0003-3344-7207
Louis FlamandDepartment of Microbiology, Infectious Disease and Immunology, Faculty of Medicine, Laval University, Quebec, QC G1V 4G2, Canada.ORCID 0000-0001-5010-4586
Sara N RichterDepartment of Molecular Medicine, University of Padua, 35121 Padua, Italy.ORCID 0000-0002-5446-9029
University of Padua · ITUniversity of Udine · ITUniversité Laval · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The herpes simplex virus 1 (HSV-1) genome is extremely rich in guanine tracts that fold into G-quadruplexes (G4s), nucleic acid secondary structures implicated in key biological functions. Viral G4s were visualized in HSV-1 infected cells, with massive virus cycle-dependent G4-formation peaking during viral DNA replication. Small molecules that specifically interact with G4s have been shown to inhibit HSV-1 DNA replication. We here investigated the antiviral activity of TMPyP4, a porphyrin known to interact with G4s. The analogue TMPyP2, with lower G4 affinity, was used as control. We showed by biophysical analysis that TMPyP4 interacts with HSV-1 G4s, and inhibits polymerase progression in vitro; in infected cells, it displayed good antiviral activity which, however, was independent of inhibition of virus DNA replication or entry. At low TMPyP4 concentration, the virus released by the cells was almost null, while inside the cell virus amounts were at control levels. TEM analysis showed that virus particles were trapped inside cytoplasmatic vesicles, which could not be ascribed to autophagy, as proven by RT-qPCR, western blot, and immunofluorescence analysis. Our data indicate a unique mechanism of action of TMPyP4 against HSV-1, and suggest the unprecedented involvement of currently unknown G4s in viral or antiviral cellular defense pathways.

Indexed as

AnimalsAntiviral AgentsCell SurvivalChlorocebus aethiopsCytoplasmic VesiclesDNA, ViralG-QuadruplexesHerpesvirus 1, HumanLigandsMolecular StructurePorphyrinsVero CellsVirionVirus ReplicationAntiviral AgentsDNA, ViralLigandsPorphyrinstetra(4-N-methylpyridyl)porphineantiviral activityG-quadruplexG-quadruplex ligandsHSV-1TMPyP2TMPyP4

Identifiers

PMID33525505
PMCPMC7911665
OpenAlexW3123301455

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.