Evidence map›Paper›PMID 35982676›Full record

ArticlebioRxiv : the preprint server for biology2022

Breathing and tilting: mesoscale simulations illuminate influenza glycoprotein vulnerabilities.

Lorenzo Casalino, Christian Seitz, Julia Lederhofer, Yaroslav Tsybovsky, Ian A Wilson, Masaru Kanekiyo, Rommie E Amaro

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

Article in bioRxiv : the preprint server for biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 5 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Lorenzo CasalinoDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093, United States.
Christian SeitzDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093, United States.
Julia LederhoferVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Yaroslav TsybovskyElectron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, United States.
Ian A WilsonDepartment of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, United States.
Masaru KanekiyoVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Rommie E AmaroDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093, United States.
University of California San Diego · USNational Institutes of Health · USFrederick National Laboratory for Cancer Research · USScripps Research Institute · US

Funding

COLLABORATIVE INFLUENZA VACCINE INNOVATION CENTER: UNIVERSAL INFLUENZA VACCINE RESEARCH75N93019C00051 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KRAMMER, FLORIAN · 2019 to 2025
$105.4M
Training in Multi-Scale Analysis of Biological Structure and FunctionT32EB009380 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrew D. McCulloch, Padmini Rangamani · 2009 to 2026
$4.8M
High-throughput assays and small-molecule discovery of antiviral candidates targeting influenza hemagglutininR01AI150885 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI Seiya Kitamura, IAN A WILSON · 2021 to 2026
$3.6M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENIAID NIH HHS 75N93019C00051NIAID NIH HHS R01 AI150885NIBIB NIH HHS T32 EB009380
6 · The paper itself

Abstract

Influenza virus has resurfaced recently from inactivity during the early stages of the COVID-19 pandemic, raising serious concerns about the nature and magnitude of future epidemics. The main antigenic targets of influenza virus are two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Whereas the structural and dynamical properties of both glycoproteins have been studied previously, the understanding of their plasticity in the whole-virion context is fragmented. Here, we investigate the dynamics of influenza glycoproteins in a crowded protein environment through mesoscale all-atom molecular dynamics simulations of two evolutionary-linked glycosylated influenza A whole-virion models. Our simulations reveal and kinetically characterize three main molecular motions of influenza glycoproteins: NA head tilting, HA ectodomain tilting, and HA head breathing. The flexibility of HA and NA highlights antigenically relevant conformational states, as well as facilitates the characterization of a novel monoclonal antibody, derived from human convalescent plasma, that binds to the underside of the NA head. Our work provides previously unappreciated views on the dynamics of HA and NA, advancing the understanding of their interplay and suggesting possible strategies for the design of future vaccines and antivirals against influenza.

Identifiers

PMID35982676
PMCPMC9387122
OpenAlexW4289711118

What OpenQuestion holds

Textmetadata
LicenceCC BY-ND
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.