3D Structure Surface Modelling From Volumetric CT Images

Pei, Yuchen; Xia, Wenjin; Wang, Xiuying; Li, Jieyu; Ye, Hongwei; Wang, Lisheng

doi:10.1109/isbi.2019.8759432

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…One antiviral approach is the development of molecules which target the assembly of virus capsids, the protective container of the viral genome. [2][3] The HBV core protein (Cp), the shell of the viral core, is implicated in virus functionality at nearly every step of the viral lifecycle, which explains why Cp is a particularly attractive antiviral target. During viral infection, core protein dimers assemble to form ordered spherical capsids with T = 3 and T = 4 icosahedral geometry, consisting of 90 and 120 dimers, respectively.…”

Section: Introductionmentioning

confidence: 99%

Competition between Normative and Drug-Induced Virus Self-Assembly Observed with Single-Particle Methods

et al. 2018

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Disruption of virus capsid assembly has compelling antiviral potential that has been applied to Hepatitis B Virus (HBV). HBV core protein assembly can be modulated by heteroaryldihydropyrimidines (HAPs), such molecules are collectively termed core protein allosteric modulators (CpAMs). Though the antiviral effects of CpAMs are acknowledged, the mechanism of action remains an open question. Challenging aspects of characterizing misdirected assembly are the large size and non-uniform nature of the final particles. In this study of HBV assembly, we observed a competition between normative and CpAM-induced aberrant assembly with electron microscopy and single particle nanofluidic techniques. This competition was a function of the strength of the association energy between individual core proteins, which is proportional to ionic strength. With strong association energy, assembly reactions primarily yielded morphologically normal HBV capsids, despite the presence of HAP. At weak association energy, HAPs led to increased assembly product size and disrupted morphology. The smallest particles were T = 4 icosahedra, whereas the larger particles were defective spheres, ellipsoids, and bacilliform cylinders, with regions of T = 4 geometry interspersed with flat regions. Deviation from the spherical T = 4 geometry progressively increased with particle size, which is consistent with the interpretation of a competition between two alternative assembly pathways.

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Section: Introductionmentioning

confidence: 99%

Competition between Normative and Drug-Induced Virus Self-Assembly Observed with Single-Particle Methods

et al. 2018

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“…5 Small molecules that disrupt the virus assembly pathway have emerged as an orthogonal approach to existing strategies. 6,7 Besides the pharmaceutical applications, the study of these assembly effectors enhances the basic knowledge of the self-assembly reaction and its mechanisms, [8][9][10][11][12] which in turn impacts the fields of virology and biomaterial science. [13][14] During HBV assembly, core protein dimers react to form the icosahedral virus capsid -the protective shell of the genome.…”

mentioning

confidence: 99%

Evolution of Intermediates during Capsid Assembly of Hepatitis B Virus with Phenylpropenamide-Based Antivirals

et al. 2019

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The self-assembly of virus capsids is a potential target for antivirals due to its importance in the virus lifecycle. Here, we investigate the effect of phenylpropenamide derivatives B-21 and AT-130 on the assembly of hepatitis B virus (HBV) core protein. Phenylpropenamides are widely believed to yield assembly of spherical particles resembling native, empty HBV capsids. Because the details of assembly can be overlooked with ensemble measurements, we performed resistive-pulse measurements on nanofluidic devices with four pores in series to characterize the size distributions of the products in real time. With its single particle sensitivity and compatibility with typical assembly buffers, resistive-pulse sensing is well suited for analyzing virus assembly in vitro. We observed that assembly with B-21 and AT-130 produced a large fraction of partially complete virus particles that may be on-path, off-path, or trapped. For both B-21 and AT-130, capsid assembly was more sensitive to disruption under conditions where the inter-protein association energy was low at lower salt concentrations. Dilution of the reaction solutions led to the rearrangement of the incomplete particles and demonstrated that these large intermediates may be on-path, but are labile, and exist in a frustrated dynamic equilibrium. During capsid assembly, phenylpropenamide molecules modestly increase the association energy of dimers, prevent intermediates from dissociating, and lead to kinetic trapping where the formation of too many capsids has been initiated leading to both empty and incomplete particles.

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3D Structure Surface Modelling From Volumetric CT Images

Cited by 2 publications

References 9 publications

Competition between Normative and Drug-Induced Virus Self-Assembly Observed with Single-Particle Methods

Competition between Normative and Drug-Induced Virus Self-Assembly Observed with Single-Particle Methods

Evolution of Intermediates during Capsid Assembly of Hepatitis B Virus with Phenylpropenamide-Based Antivirals

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