Neutrons key to discovering new HIV drugs? An interview with Dr Matthew Blakeley

THOUGHT LEADERS SERIES...insight from the world’s leading experts.
A. Cashin-Garbutt. News-Medical Life Sciences, July 2016; https://www.news-medical.net/news/20160721/Neutrons-key-to-discovering-new-HIV-drugs-An-interview-with-Dr-Matthew-Blakeley.aspx

Neutrons probe structure of enzyme critical to development of next-generation HIV drugs

A team led by the Department of Energy's Oak Ridge National Laboratory used neutron analysis to better understand a protein implicated in the replication of HIV, the retrovirus that causes AIDS.
J. Rumsey. Phys.org, May 2016; https://phys.org/news/2016-05-neutrons-probe-enzyme-critical-next-generation.html

Fighting HIV with neutrons

When thinking about diffraction studies, X-rays most often come to mind, but neutrons can also provide important structural information – and could help in the fight against HIV.
M. Blakely. Science in School, February 2015; https://www.scienceinschool.org/content/fighting-hiv-neutrons

Neutron study aims to improve HIV drugs

A neutron study of a common component of HIV drugs has revealed that the component is not as good at bonding as had been thought.
J. Cartwright. Physics World, August 2013; https://physicsworld.com/a/neutron-study-aims-to-improve-hiv-drugs/

In the Spotlight: Neutron Crystallography

The potential has been acutely demonstrated in a recent study of interactions between a common clinical inhibitor and HIV-1 protease – an enzyme essential for the replication of the virus.
European Biopharmaceutical Review, Spring 2014; http://www.samedanltd.com/magazine/12/issue/215/article/3787

Neutron crystallography aids in drug design

Neutron crystallography can prove vital towards a better understanding of many biological processes, such as enzyme mechanisms and can help guide structure-based drug design.
International Union of Crystallography. ScienceDaily, September 2016; https://www.sciencedaily.com/releases/2016/09/160907112353.htm

Visualizing Tetrahedral Oxyanion Bound in HIV-1 Protease Using Neutrons: Implications for the Catalytic Mechanism and Drug Design

Mukesh Kumar, Kalyaneswar Mandal, Matthew P. Blakeley, Troy Wymore, Stephen B. H. Kent, John M. Louis, Amit Das, and Andrey Kovalevsky. ACS Omega 2020; https://doi.org/10.1021/acsomega.0c00835

Proton transfer and drug binding details revealed in neutron diffraction studies of wild-type and drug resistant HIV-1 protease

Kovalevsky A, Gerlits O, Beltran K, Weiss KL, Keen DA, Blakeley MP, Louis JM, Weber IT. Methods Enzymol. (2020) 634, 257-279; https://doi.org/10.1016/bs.mie.2019.12.002

Structure determination of the myristoylated human immunodeficiency virus-1 (HIV-1) Gag matrix

Biointerphases 12, 02D408 (2017); https://doi.org/10.1116/1.4983155

Room temperature neutron crystallography of drug resistant HIV-1 protease uncovers limitations of X-ray structural analysis at 100K

Gerlits OO, Keen DA, Blakeley MP, Louis JM, Weber IT, Kovalevsky AY. J. Medicinal Chemistry (2017) 60(5): 2018–2025; https://doi.org/10.1021/acs.jmedchem.6b01767

Joint X-ray/neutron crystallographic study of HIV-1 protease with clinical inhibitor amprenavir – insights for drug design

Weber IT, Waltman MJ, Mustyakimov M, Blakeley MP, Keen DA, Ghosh AK, Langan P, Kovalevsky AY. J. Medicinal Chemistry (2013) 56(13): 5631–5635; https://doi.org/10.1021/jm400684f

The helix-to-sheet transition of an HIV-1 fusion peptide derivative changes the mechanical properties of lipid bilayer membranes

William T. Heller, Piotr A. Zolnierczuk; https://doi.org/10.1016/j.bbamem.2018.12.004

Influenza and SANS: Large-Scale Conformational Dynamics Control H5N1 Influenza Polymerase PB2 Binding to Importin α
J. Am. Chem. Soc. 2015, 137, 48, 15122-15134
https://doi.org/10.1021/jacs.5b07765

Combined results from solution studies on intact influenza virus M1 protein and from a new crystal form of its N-terminal domain show that M1 is an elongated monomer
Arzt S., Baudin F., Barge A., Timmins P.A., Burmeister W.P., Ruigrok R.W.H. Virology 279, 439-446 (2001)
https://doi.org/10.1006/viro.2000.0727

Successful reprogramming of cellular protein production through mRNA delivered by functionalized lipid nanoparticles

Arteta MY, Kjellman T, Bartesaghi S, Wallin S, Wu X, Kvist AJ, Dabkowska A, Székely N, Radulescu A, Bergenholtz J, Lindfors L. PNAS (2018) 115(15): E3351–E3360; https://pubmed.ncbi.nlm.nih.gov/29588418/

Investigation of charge ratio variation in mRNA – DEAE-dextran polyplex delivery systems

C. Siewert, H. Haas, T. Nawroth, A. Ziller, S.S. Nogueira, M.A. Schroer, C.E. Blanchet, D.I. Svergun, A. Radulescu, F. Bates, Y. Huesemann, M.P. Radsak, U. Sahin, P. Langguth. Biomaterials 192 (2019) 612–620; https://doi.org/10.1016/j.biomaterials.2018.10.

ESS Data Scientist helps shed light on assembly mechanism of hepatitis B virus, ESS website
Ryan C. Oliver, Wojciech Potrzebowski, Seyed Morteza Najibi, Martin Nors Pedersen, Lise Arleth, Najet Mahmoudi, and Ingemar André. "Assembly of Capsids from Hepatitis B Virus Core Protein Progresses through Highly Populated Intermediates in the Presence and Absence of RNA". ACS Nano 2020, 14, 8, 10226–10238.
https://doi.org/10.1021/acsnano.0c03569

Coupling neutron reflectivity with cell-free protein synthesis to probe membrane protein structure in supported bilayers
Soranzo, T., Martin, D.K., Lenormand, J. et al. Coupling neutron reflectivity with cell-free protein synthesis to probe membrane protein structure in supported bilayers. Sci Rep 7, 3399 (2017).
https://doi.org/10.1038/s41598-017-03472-8

Neutrons reveal hidden secrets of the hepatitis C virus
https://www.ill.eu/news-press-events/press-corner/press-releases/neutrons-reveal-hidden-secrets-of-the-hepatitis-c-virus/

Intrinsic disorder in measles virus nucleocapsids
Jensen M.R., Communie G., Ribeiro Jr E.A., Martinez N., Desfosses A., Salmon L., Mollica L., Gabel F., Jamin M., Longhi S., Ruigrok R.W., Blackledge M. Proceedings of the National Academy of Sciences of the USA 108, 9839-9844 (2011)
https://doi.org/10.1073/pnas.1103270108

Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type I glycoprotein gH occurs through a cholesterol-dependent mechanism
Giuseppe Vitiello, Annarita Falanga, Ariel Alcides Petruk, Antonello Merlino, Giovanna Fragneto, Luigi Paduano, Stefania Galdiero, Gerardino D’Errico. Soft Matter 02/2015.
https://doi.org/10.1039/C4SM02769H

Cholesterol modulates the fusogenic activity of a membranotropic domain of the FIV glycoprotein gp36
Giuseppe Vitiello, Giovanna Fragneto, Ariel Alcides Petruk, Annarita Falanga, Stefania Galdiero, Anna Maria D ‘ursi, Antonello Merlino, Gerardino D Errico. Soft Matter 2013.
https://doi.org/10.1039/C3SM50553G

Destabilization of Lipid Membranes by a Peptide Derived from Glycoprotein gp36 of Feline Immunodeficiency Virus: A Combined Molecular Dynamics/Experimental Study
A. Merlino, G. Vitiello, M. Grimaldi, F. Sica, E. Busi, R. Basosi, A. M. D’Ursi, G. Fragneto, L. Paduano, and G. D’Errico
J. Phys. Chem. B, 2012, 116 (1), pp 401–412
https://doi.org/10.1021/jp204781a

Ensemble structure of the highly flexible complex formed between vesicular stomatitis virus unassembled nucleoprotein and its phosphoprotein chaperone
Yabukarski F., Leyrat C., Martinez N., Communie G., Ivanov I., Ribeiro E.A., Buisson M., Gérard F.C., Bourhis J.M., Jensen M.R., Bernadó P., Blackledge M., Jamin M. Journal of Molecular Biology 428, 2671-2694 (2016)
https://doi.org/10.1016/j.jmb.2016.04.010