☆ 4.8 Article

High flavivirus structural plasticity demonstrated by a non-spherical morphological variant

NATURE COMMUNICATIONS (2020)

Journal

NATURE COMMUNICATIONS

Volume 11, Issue 1, Pages -

Publisher

NATURE PORTFOLIO

DOI: 10.1038/s41467-020-16925-y

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Multidisciplinary Sciences

Funding

National Research Foundation Investigatorship award [NRF-NRFI2016-01]
National Research Foundation competitive Research Project [NRF2016NRF-CRP001-063]
Duke-NUS Signature Research Programme - Ministry of Health, Singapore
Public Health Service grants from the National Institutes of Health, USA [GM122979, GM127365]

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Abstract

Previous flavivirus (dengue and Zika viruses) studies showed largely spherical particles either with smooth or bumpy surfaces. Here, we demonstrate flavivirus particles have high structural plasticity by the induction of a non-spherical morphology at elevated temperatures: the club-shaped particle (clubSP), which contains a cylindrical tail and a disc-like head. Complex formation of DENV and ZIKV with Fab C10 stabilize the viruses allowing cryoEM structural determination to similar to 10 angstrom resolution. The caterpillar-shaped (catSP) Fab C10:ZIKV complex shows Fabs locking the E protein raft structure containing three E dimers. However, compared to the original spherical structure, the rafts have rotated relative to each other. The helical tail structure of Fab C10:DENV3 clubSP showed although the Fab locked an E protein dimer, the dimers have shifted laterally. Morphological diversity, including clubSP and the previously identified bumpy and smooth-surfaced spherical particles, may help flavivirus survival and immune evasion.

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Article Infectious Diseases

Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial

Xinxue Liu, Alasdair P. S. Munro, Shuo Feng, Leila Janani, Parvinder K. Aley, Gavin Babbage, David Baxter, Marcin Bula, Katrina Cathie, Krishna Chatterjee, Wanwisa Dejnirattisai, Kate Dodd, Yvanne Enever, Ehsaan Qureshi, Anna L. Goodman, Christopher A. Green, Linda Harndahl, John Haughney, Alexander Hicks, Agatha A. van der Klaauw, Jonathan Kwok, Vincenzo Libri, Martin J. Llewelyn, Alastair C. McGregor, Angela M. Minassian, Patrick Moore, Mehmood Mughal, Yama F. Mujadidi, Kyra Holliday, Orod Osanlou, Rostam Osanlou, Daniel R. Owens, Mihaela Pacurar, Adrian Palfreeman, Daniel Pan, Tommy Rampling, Karen Regan, Stephen Saich, Teona Serafimova, Dinesh Saralaya, Gavin R. Screaton, Sunil Sharma, Ray Sheridan, Ann Sturdy, Piyada Supasa, Emma C. Thomson, Shirley Todd, Chris Twelves, Robert C. Read, Sue Charlton, Bassam Hallis, Mary Ramsay, Nick Andrews, Teresa Lambe, Jonathan S. Nguyen-Van-Tam, Victoria Cornelius, Matthew D. Snape, Saul N. Faust

Summary: The decay rates of humoral response differ between vaccines 84 days after a third dose of COVID-19 vaccine. The anti-spike IgG concentrations following BNT/BNT initial doses were similar to or higher than for a three-dose BNT schedule. Half dose BNT immune responses were similar to full dose responses.

JOURNAL OF INFECTION (2022)

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Article Microbiology

Analysis of SARS-CoV-2 in Nasopharyngeal Samples from Patients with COVID-19 Illustrates Population Variation and Diverse Phenotypes, Placing the Growth Properties of Variants of Concern in Context with Other Lineages

Tessa Prince, Xiaofeng Dong, Rebekah Penrice-Randal, Nadine Randle, Catherine Hartley, Hannah Goldswain, Benjamin Jones, Malcolm G. Semple, J. Kenneth Baillie, Peter J. M. Openshaw, Lance Turtle, Grant L. Hughes, Enyia R. Anderson, Edward Patterson, Julian Druce, Gavin Screaton, Miles W. Carroll, James P. Stewart, Julian A. Hiscox

Summary: New variants of SARS-CoV-2 are continuously emerging. Understanding virus evolution and selection pressures requires considering population dynamics and new variants.

MSPHERE (2022)

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Article Medicine, General & Internal

The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 beta (B.1.351) and other variants of concern in preclinical studies

Alexandra J. Spencer, Susan Morris, Marta Ulaszewska, Claire Powers, Reshma Kailath, Cameron Bissett, Adam Truby, Nazia Thakur, Joseph Newman, Elizabeth R. Allen, Indra Rudiansyah, Chang Liu, Wanwisa Dejnirattisai, Juthathip Mongkolsapaya, Hannah Davies, Francesca R. Donnellan, David Pulido, Thomas P. Peacock, Wendy S. Barclay, Helen Bright, Kuishu Ren, Gavin Screaton, Patrick McTamney, Dalan Bailey, Sarah C. Gilbert, Teresa Lambe

Summary: This study describes the generation and preclinical assessment of a vaccine targeting Beta VoC (B.1.351), which shows immunogenicity after a single dose and produces antibody responses to other variants as a booster, along with a strong T cell response.

EBIOMEDICINE (2022)

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Article Chemistry, Physical

Glycine Substitution of Residues with Unfavored Dihedral Angles Improves Protein Thermostability

Zhili Lu, Qiaoxian Zhong, Jingxian Li, Bingjie Zhou, Yan-Ni Xing, Kaien Liu, Kexin Cao, Dongming Lan, Teng Zhou, Yonghua Wang, Jiaqi Wang

Summary: This study used computational approaches and mutagenesis strategies to enhance the stability of a diacylglycerol-specific lipase. Several mutations were found to significantly improve the thermostability and enzymatic activity of the enzyme. Structural analysis revealed how these mutations can release steric strain and increase stability. This suggests that substitution with glycine could be a promising strategy for improving protein thermostability.

CATALYSTS (2022)

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