Publications

Notable Recent Publications

These are some recent publications which give a flavour of the research from the Barclay lab. For a complete list of publications, please see below.

Species difference in ANP32A underlies influenza A virus polymerase host restriction. Nature (2016).
Jason S. Long, Efstathios S. Giotis, Olivier Moncorgé, Rebecca Frise, Bhakti Mistry, Joe James, Mireille Morisson, Munir Iqbal, Alain Vignal, Michael A. Skinner & Wendy S. Barclay

This paper identified a key factor that explained why the polymerases from avian influenza viruses are restricted in humans.  For more, please see the associated New and Views.

See our latest ANP32 papers here: eLIFE, Journal of Virology, Journal of Virology.

The mechanism of resistance to favipiravir in influenza. PNAS (2018).
Daniel H. Goldhill, Aartjan J. W. te Velthuis, Robert A. Fletcher, Pinky Langat, Maria Zambon, Angie Lackenby & Wendy S. Barclay

This paper showed how influenza could evolve resistance to favipiravir, an antiviral that may be used to treat influenza. The residue that mutated to give resistance was highly conserved suggesting that the mechanism of resistance may be applicable to other RNA viruses.

Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice. Plos Path. (2018).
Hui Li*, Konrad C. Bradley*, Jason S. Long, Rebecca Frise, Jonathan W. Ashcroft, Lorian C. Hartgroves, Holly Shelton, Spyridon Makris, Cecilia Johansson, Bin Cao & Wendy S. Barclay

Why do avian influenza viruses like H5N1 cause such severe disease in humans? This paper demonstrated that H5N1 viruses replicate better than human viruses in myeloid cells from mice leading to a cytokine storm and more severe disease.

Citation

BibTex format

@article{Lesch:2019:10.1371/journal.ppat.1007601,
author = {Lesch, M and Luckner, M and Meyer, M and Weege, F and Gravenstein, I and Raftery, M and Sieben, C and Martin-Sancho, L and Imai-Matsushima, A and Welke, R-W and Frise, R and Barclay, W and Schoenrich, G and Herrmann, A and Meyer, TF and Karlas, A},
doi = {10.1371/journal.ppat.1007601},
journal = {PLoS Pathogens},
pages = {1--34},
title = {RNAi-based small molecule repositioning reveals clinically approved urea-based kinase inhibitors as broadly active antivirals},
url = {http://dx.doi.org/10.1371/journal.ppat.1007601},
volume = {15},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Influenza viruses (IVs) tend to rapidly develop resistance to virus-directed vaccines and common antivirals targeting pathogen determinants, but novel host-directed approaches might preclude resistance development. To identify the most promising cellular targets for a host-directed approach against influenza, we performed a comparative small interfering RNA (siRNA) loss-of-function screen of IV replication in A549 cells. Analysis of four different IV strains including a highly pathogenic avian H5N1 strain, an influenza B virus (IBV) and two human influenza A viruses (IAVs) revealed 133 genes required by all four IV strains. According to gene enrichment analyses, these strain-independent host genes were particularly enriched for nucleocytoplasmic trafficking. In addition, 360 strain-specific genes were identified with distinct patterns of usage for IAVs versus IBV and human versus avian IVs. The strain-independent host genes served to define 43 experimental and otherwise clinically approved drugs, targeting reportedly fourteen of the encoded host factors. Amongst the approved drugs, the urea-based kinase inhibitors (UBKIs) regorafenib and sorafenib exhibited a superior therapeutic window of high IV antiviral activity and low cytotoxicity. Both UBKIs appeared to block a cell signaling pathway involved in IV replication after internalization, yet prior to vRNP uncoating. Interestingly, both compounds were active also against unrelated viruses including cowpox virus (CPXV), hantavirus (HTV), herpes simplex virus 1 (HSV1) and vesicular stomatitis virus (VSV) and showed antiviral efficacy in human primary respiratory cells. An in vitro resistance development analysis for regorafenib failed to detect IV resistance development against this drug. Taken together, the otherwise clinically approved UBKIs regorafenib and sorafenib possess high and broad-spectrum antiviral activity along with substantial robustness against resistance development and thus constitute attractive hos
AU  - Lesch,M
AU  - Luckner,M
AU  - Meyer,M
AU  - Weege,F
AU  - Gravenstein,I
AU  - Raftery,M
AU  - Sieben,C
AU  - Martin-Sancho,L
AU  - Imai-Matsushima,A
AU  - Welke,R-W
AU  - Frise,R
AU  - Barclay,W
AU  - Schoenrich,G
AU  - Herrmann,A
AU  - Meyer,TF
AU  - Karlas,A
DO  - 10.1371/journal.ppat.1007601
EP  - 34
PY  - 2019///
SN  - 1553-7366
SP  - 1
TI  - RNAi-based small molecule repositioning reveals clinically approved urea-based kinase inhibitors as broadly active antivirals
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1007601
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000462996700015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007601
UR  - http://hdl.handle.net/10044/1/75921
VL  - 15
ER  -
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