scholarly journals Structural Biology of Nanobodies against the Spike Protein of SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2214
Author(s):  
Qilong Tang ◽  
Raymond J. Owens ◽  
James H. Naismith
Keyword(s):  
Structural Biology ◽  
Molecular Size ◽  
Structural Features ◽  
Spike Protein ◽  
Biomedical Sciences ◽  
Blood Disorder ◽  
Animal Trials ◽  
Short Period ◽  
Single Domain Antibodies ◽  
Scientific Endeavour

Nanobodies are 130 amino acid single‑domain antibodies (VHH) derived from the unique heavy-chain-only subclass of Camelid immunogloblins. Their small molecular size, facile expression, high affinity and stability have combined to make them unique targeting reagents with numerous applications in the biomedical sciences. The first nanobody agent has now entered the clinic as a treatment against a blood disorder. The spread of the SARS-CoV-2 virus has seen the global scientific endeavour work to accelerate the development of technologies to try to defeat a pandemic that has now killed over four million people. In a remarkably short period of time, multiple studies have reported nanobodies directed against the viral Spike protein. Several agents have been tested in culture and demonstrate potent neutralisation of the virus or pseudovirus. A few agents have completed animal trials with very encouraging results showing their potential for treating infection. Here, we discuss the structural features that guide the nanobody recognition of the receptor binding domain of the Spike protein of SARS-CoV-2.

Computational Study for Molecular Properties of Some of the Isolated Chemicals from Leaves Extract of Guiera Senegalensis as Aluminium Corrosion Inhibitor

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
A. M. Ayuba ◽  
◽  
M. Abubakar ◽  
Keyword(s):  
Molecular Dynamics ◽  
Quantum Chemical ◽  
Energy Gap ◽  
Computational Study ◽  
Physical Adsorption ◽  
Chemical Constituents ◽  
Molecular Size ◽  
Structural Features ◽  
Inhibitor Molecule ◽  
Fukui Indices

The present work describes the computational methods for the corrosion inhibition of aluminium using three selected chemical constituents (5-methyldihydroflavasperone, 5-methylflavasperone and methoxylated naphthyl butanone) reportedly obtained from the leaves extract of Guirea senegalensis. Quantum chemical calculations including EHOMO, ELUMO, energy gap (ΔE), electronegativity (χ), global hardness (η) and fraction of electrons transfer from the inhibitor molecule to the aluminium surface (ΔN) were calculated. The local reactive sites through Fukui indices which explain the effect of structural features of these components in relation to electrophilic and nucleophilic point of attack were evaluated. The similarities in quantum chemical parameters for the compounds obtained revealed that the adsorption strengths of the molecules will be mostly determined by molecular size rather than electronic structure parameters. Fukui indices showed that the point of interaction of inhibitor molecule with the Al(l10) surface were through aromatic carbon atom rich in pi-electrons and oxygen atom of the alkanone functional group in the inhibitor molecules. Molecular dynamics simulations describing the adsorption behavior of the inhibitor molecule on Al(110) surface through Forcite quench molecular dynamics were carried out. The compounds were found to all obey the mechanism of physical adsorption because of their relatively low adsorption energies.

Structure of Polybutadienes

1967 ◽  
Vol 40 (5) ◽  
pp. 1529-1543 ◽  
Author(s):  
W. S. Bahary ◽  
D. I. Sapper
Keyword(s):  
Light Scattering ◽  
Molecular Size ◽  
Structural Features ◽  
Melting Point Depression ◽  
Linear Polymers ◽  
Long Chain Branching ◽  
Molecular Weights ◽  
Catalyst Systems ◽  
Molecular Size Distribution

Abstract Polybutadienes made with six different catalyst systems were examined: (1) butyllithium, (2) “nickel-based”, (3) alfin, (4) “titanium-based”, (5) “cobalt-based”, and (6) free radical emulsion. The microstructure and macrostructure of the polybutadienes have been determined and are compared to the results published in the literature. These polybutadienes may be considered to be random terpolymers of cis, trans, and vinyl addition of butadiene. The glass transition temperature is specified by the vinyl content. The crystalline melting points of the high trans and also the high cis polybutadienes obey to a high measure Flory's equation for melting point depression of a random terpolymer. The molecular weights of the polybutadienes have been determined by light scattering and osmometry and the degree of long chain branching has been determined by the branching index, 〈g′〉. The macro-structural features of the linear polymers are confirmed by fractionation. However, the polydispersities calculated from fractionation data do not agree with those determined from light scattering and osmometry for the branched samples. The discrepancy is attributed to the method of characterization of the fractions. A distinction is made between molecular weight distribution and molecular size distribution.

scholarly journals A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19

2021 ◽  
Author(s):  
Raymond Owens ◽  
Jiandong Huo ◽  
Halina Mikolajek ◽  
Audrey Le Bas ◽  
Jordan Clark ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Unmet Need ◽  
Spike Protein ◽  
Protein Crystal ◽  
Hamster Model ◽  
Cryo Electron Microscopy ◽  
Effective Prophylaxis ◽  
Escape Mutants ◽  
Single Domain Antibodies ◽  
Global Threat

Abstract SARS-CoV-2 remains a global threat to human health particularly as escape mutants emerge. There is an unmet need for effective treatments against COVID-19 for which neutralizing single domain antibodies (nanobodies) have significant potential. Their small size and stability mean that nanobodies are compatible with respiratory administration. We report four nanobodies (C5, H3, C1, F2) engineered as homotrimers with pmolar affinity for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Crystal structures show C5 and H3 overlap the ACE2 epitope, whilst C1 and F2 bind to a different epitope. Cryo Electron Microscopy shows C5 binding results in an all down arrangement of the Spike protein. C1, H3 and C5 all neutralize the Victoria strain, and the highly transmissible Alpha (B.1.1.7 first identified in Kent, UK) strain and C1 also neutralizes the Beta (B.1.35, first identified in South Africa). Administration of C5-trimer via the respiratory route showed potent therapeutic efficacy in the Syrian hamster model of COVID-19 and separately effective prophylaxis. The molecule was similarly potent by intraperitoneal injection.

scholarly journals Single-Domain Antibodies as Therapeutic and Imaging Agents for the Treatment of CNS Diseases

Antibodies ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 27 ◽  
Author(s):  
Kasandra Bélanger ◽  
Umar Iqbal ◽  
Jamshid Tanha ◽  
Roger MacKenzie ◽  
Maria Moreno ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Building Blocks ◽  
Structural Features ◽  
Antibody Fragments ◽  
Single Domain ◽  
Imaging Agents ◽  
Cns Diseases ◽  
Single Domain Antibodies ◽  
Potential Therapeutics ◽  
Brain Barriers

Antibodies have become one of the most successful therapeutics for a number of oncology and inflammatory diseases. So far, central nervous system (CNS) indications have missed out on the antibody revolution, while they remain ‘hidden’ behind several hard to breach barriers. Among the various antibody modalities, single-domain antibodies (sdAbs) may hold the ‘key’ to unlocking the access of antibody therapies to CNS diseases. The unique structural features of sdAbs make them the smallest monomeric antibody fragments suitable for molecular targeting. These features are of particular importance when developing antibodies as modular building blocks for engineering CNS-targeting therapeutics and imaging agents. In this review, we first introduce the characteristic properties of sdAbs compared to traditional antibodies. We then present recent advances in the development of sdAbs as potential therapeutics across brain barriers, including their use for the delivery of biologics across the blood–brain and blood–cerebrospinal fluid (CSF) barriers, treatment of neurodegenerative diseases and molecular imaging of brain targets.

scholarly journals Challenges and perspectives for structural biology of lncRNAs—the example of the Xist lncRNA A-repeats

2019 ◽  
Vol 11 (10) ◽  
pp. 845-859 ◽  
Author(s):  
Alisha N Jones ◽  
Michael Sattler
Keyword(s):  
High Resolution ◽  
Structural Biology ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Structural Features ◽  
Molecular Features

Abstract Following the discovery of numerous long non-coding RNA (lncRNA) transcripts in the human genome, their important roles in biology and human disease are emerging. Recent progress in experimental methods has enabled the identification of structural features of lncRNAs. However, determining high-resolution structures is challenging as lncRNAs are expected to be dynamic and adopt multiple conformations, which may be modulated by interaction with protein binding partners. The X-inactive specific transcript (Xist) is necessary for X inactivation during dosage compensation in female placental mammals and one of the best-studied lncRNAs. Recent progress has provided new insights into the domain organization, molecular features, and RNA binding proteins that interact with distinct regions of Xist. The A-repeats located at the 5′ end of the transcript are of particular interest as they are essential for mediating silencing of the inactive X chromosome. Here, we discuss recent progress with elucidating structural features of the Xist lncRNA, focusing on the A-repeats. We discuss the experimental and computational approaches employed that have led to distinct structural models, likely reflecting the intrinsic dynamics of this RNA. The presence of multiple dynamic conformations may also play an important role in the formation of the associated RNPs, thus influencing the molecular mechanism underlying the biological function of the Xist A-repeats. We propose that integrative approaches that combine biochemical experiments and high-resolution structural biology in vitro with chemical probing and functional studies in vivo are required to unravel the molecular mechanisms of lncRNAs.

scholarly journals Structure and morphogenesis of shoots of species of the genus Viburnum L. in the Right-Bank Forest-Steppe of Ukraine

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
O. O. Demchenko
Keyword(s):  
Shoot Growth ◽  
Structural Features ◽  
Annual Growth ◽  
Forest Steppe ◽  
Structure And Dynamics ◽  
Short Period ◽  
Sum Of Effective Temperatures ◽  
The Right ◽  
Intensive Growth

The research was conducted on the structure and characteristics of the growth of shoots of the genus Viburnum L. There are significant differences in the structure and dynamics of growth within the genus, so the determination of the structural features of the shoots of species of the genus Viburnum is relevant. The research of the dynamics of shoot growth was carried out according to the method of A.A. Molchanov and V.V. Smirnov (1967). The species studied by us belong to three sections of the genus Viburnum; the peculiarities of buds structure generally determine the structure of the shoots in the species of each section. It was found that the type of each of the three sections of the genus is characterized by a special structure of the shoots. It has been studied the rhythm of growth and development of native and introduced species of the genus Viburnum L. The terms of shoots growth of the species of the genus were analyzed, and the length of the annual growth of shoots was determined. Phenological date of the beginning and end of shoot growth was established. It was revealed that the onset of individual phenophases quite clearly correlates with the sum of effective temperatures above 5 ° C. The species of the genus Viburnum are characterized by the following types of shoots: tillering, stem, generative. Intensive growth of shoots of all studied species occurs in May - mid-June. In the species of the section Lantana, there are 2 peaks of shoot growth - May and mid-July. According to the duration of growth of shoots, viburnum can be divided into two groups: 1) with a short period of growth (65 - 75 days): V.opulus L., V.sargentii Koehne, V.prunifolium L., V.rufidulum Raf., V.lentago L; 2) with a long period of growth (100 or more days): V.lantana L., V.carlesii Hemsl., V.veitchii C.H. Wright, V.rhytidophyllum Hemsl., V.buddleifolium C.H. Wright, V.burejaeticum Rgl. et Herd. The data obtained demonstrated that the greatest annual growth of all Viburnum species was recorded at the age of 4-7 years. A decrease in the annual growth of axial shoots states the need for works on preliminary rejuvenation of the bush.

scholarly journals Assessment of 3D MINFLUX data for quantitative structural biology in cells

2021 ◽  
Author(s):  
Kirti Prakash ◽  
Alistair Curd
Keyword(s):  
Quantitative Analysis ◽  
Structural Biology ◽  
Single Molecule ◽  
Structural Features ◽  
Localization Microscopy ◽  
Current State ◽  
New Development ◽  
Very High ◽  
Single Molecule Localization Microscopy ◽  
In Cells

MINFLUX is a promising new development in single-molecule localization microscopy, claiming a resolution of 1-3 nm in living and fixed biological specimens. While MINFLUX can achieve very high localisation precision, quantitative analysis of reported results leads us to dispute the resolution claim and question reliability for imaging sub-100-nm structural features, in its current state.

scholarly journals Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery

2021 ◽  
Vol 15 (1) ◽  
pp. 12
Author(s):  
R. N. V. Krishna Deepak ◽  
Ravi Kumar Verma ◽  
Yossa Dwi Hartono ◽  
Wen Shan Yew ◽  
Hao Fan
Keyword(s):  
Ligand Binding ◽  
Structural Biology ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Structural Features ◽  
Structure Based Drug Design ◽  
Bovine Rhodopsin ◽  
Receptor Dynamics ◽  
Ligand Interactions ◽  
Approaches To Study

Great progress has been made over the past decade in understanding the structural, functional, and pharmacological diversity of lipid GPCRs. From the first determination of the crystal structure of bovine rhodopsin in 2000, much progress has been made in the field of GPCR structural biology. The extraordinary progress in structural biology and pharmacology of GPCRs, coupled with rapid advances in computational approaches to study receptor dynamics and receptor-ligand interactions, has broadened our comprehension of the structural and functional facets of the receptor family members and has helped usher in a modern age of structure-based drug design and development. First, we provide a primer on lipid mediators and lipid GPCRs and their role in physiology and diseases as well as their value as drug targets. Second, we summarize the current advancements in the understanding of structural features of lipid GPCRs, such as the structural variation of their extracellular domains, diversity of their orthosteric and allosteric ligand binding sites, and molecular mechanisms of ligand binding. Third, we close by collating the emerging paradigms and opportunities in targeting lipid GPCRs, including a brief discussion on current strategies, challenges, and the future outlook.

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