Evidence map›Paper›PMID 32181359›Full record

ArticleScience advances2020

Viral evolution identifies a regulatory interface between paramyxovirus polymerase complex and nucleocapsid that controls replication dynamics.

Julien Sourimant, Vidhi D Thakkar, Robert M Cox, Richard K Plemper

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.2field-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

12 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

4 authors at 1 institution in 1 country.

Julien SourimantInstitute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.ORCID 0000-0002-1660-1666
Vidhi D ThakkarInstitute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
Robert M CoxInstitute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
Richard K PlemperInstitute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.ORCID 0000-0003-2034-2107
Georgia State University · US

Funding

Identification and Pre-Clinical Evaluation of Measles Virus InhibitorsR01AI071002 · NIAID · GEORGIA STATE UNIVERSITY · PI PLEMPER, RICHARD K. · 2006 to 2022
$6.6M
Development of a Broad-Spectrum Inhibitor against Seasonal and Highly-Pathogenic Influenza VirusesR01AI141222 · NIAID · GEORGIA STATE UNIVERSITY · PI PLEMPER, RICHARD K. · 2019 to 2023
$5.0M
Novel Therapeutics against Respiratory Syncytial Virus InfectionR01HD079327 · NICHD · GEORGIA STATE UNIVERSITY · PI PLEMPER, RICHARD K. · 2014 to 2018
$2.8M
NIAID NIH HHS R01 AI071002NIAID NIH HHS R01 AI141222NICHD NIH HHS R01 HD079327
6 · The paper itself

Abstract

Paramyxoviruses are negative-polarity RNA viruses of major clinical importance. The dynamic interaction of the RNA-dependent RNA polymerase (RdRP) complex with the encapsidated RNA genome is mechanistically and structurally poorly understood. Having generated recombinant measles (MeV) and canine distemper (CDV) viruses with truncated nucleocapsid (N) protein showing defects in replication kinetics, we have applied a viral evolution approach to the problem. Passaging of recombinants resulted in long-range compensatory mutations that restored RdRP bioactivity in minigenome assays and efficient replication of engineered viruses. Compensatory mutations clustered at an electronically compatible acidic loop in N-core and a basic face of the phosphoprotein X domain (P-XD). Co-affinity precipitations, biolayer interferometry, and molecular docking revealed an electrostatic-driven transiently forming interface between these domains. The compensatory mutations reduced electrostatic compatibility of these microdomains and lowered coprecipitation efficiency, consistent with a molecular checkpoint function that regulates paramyxovirus polymerase mobility through modulation of conformational stability of the P-XD assembly.

Indexed as

AnimalsBinding SitesCell LineChlorocebus aethiopsCloning, MolecularCricetulusDistemper Virus, CanineEpithelial CellsEscherichia coliGene ExpressionMeasles virusMolecular Docking SimulationMutationNucleocapsid ProteinsPhosphoproteinsProtein BindingNucleocapsid ProteinsPhosphoproteinsRecombinant ProteinsRNA-Dependent RNA Polymerase

Identifiers

PMID32181359
PMCPMC7056317
OpenAlexW3009438914

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.