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Introduction to Cells, DNA, and Viruses
Published in Patricia G. Melloy, Viruses and Society, 2023
Finally, virologists who observe viral particles in tissues might turn to microscopy techniques such as electron microscopy and fluorescence microscopy to study viral protein structure and their interaction with cells. Because of the high magnification and resolution capability of electron microscopy, this microscopy technique has historically been used most often to visualize viruses (Figure 1.5) (Alberts et al. 2019; Lostroh 2019). The techniques of atomic force microscopy and a specialized type of electron microscopy called cryo-electron microscopy are often used as well. Superresolution microscopy has increased the capabilities of light microscopy as well (Nobel Prize Outreach AB 2014). However, cellular changes resulting from viral infection can be observed using conventional light microscopy and have been used even before the viral particles themselves could be visualized (Lostroh 2019).
Roundabouts
Published in John R. Helliwell, The Whats of a Scientific Life, 2019
Are there other options rather than repeat the whole circle of experiments again? One can try a method altogether different than X-ray crystal structure analysis. A method that has improved a lot in the last ten years or so in my field of structural chemistry and biology is that of cryo electron microscopy. In this case, a crystal is not needed and instead multiple images of a single molecular complex are studied directly. This new method has allowed the breaking out of going round in circles for those impossible-to-crystallise cases. Why were they impossible to crystallise? This could be for a variety of reasons. Firstly, although a homogenously pure sample of these molecules could be prepared, they can each be too flexible to crystallise in a simple, repeating, 3D array. Secondly, it may not have been possible to prepare a pure enough sample for crystallisation. So important is the improved method of cryo electron microscopy for the field of structural biochemistry and structural biology that its lead developers shared the Nobel Prize for Chemistry in 2017: Jacques Dubochet, Joachim Frank and Richard Henderson [2].
Instrumentation
Published in Clive R. Bagshaw, Biomolecular Kinetics, 2017
Electron microscopy has long been used to study the gross shape of protein and DNA molecules. The method has taken on increasing importance when applied to unstained hydrated samples under cryo-conditions, where domains and secondary structure and even side chains have been resolved [583,584]. Electron microscopy readily resolves single molecules, although this method has generally not been considered as a “single-molecule” kinetic technique because individual molecules cannot be followed in real time once they are fixed or frozen. However, progress has been made in real-time imaging of wet samples using a thin environmental chamber to isolate the sample from the vacuum of the microscope [585]. Using gold-labeled antibodies as a probe, images have been acquired with 0.1 s time resolution [586,587]. To follow reactions discontinuously using conventional electron microscopy, reactants are rapidly mixed in solution and then rapidly quenched by freezing, akin to that used for EPR spectroscopy (see Section 7.6.5). Devices have been constructed to spray a grid with the reactants and quickly plunge the grid in to liquid ethane to stop the reaction [583,588–591]. The sample is then examined in the frozen state by cryo-electron microscopy methods. The method has a dead time of about 5 ms. Because molecules are viewed from a range of orientations, individual molecules are classified according to their orientation before averaging with similar molecules. This approach has the power to resolve different conformational states within the same ensemble sample, which may indicate dynamics. However, kinetic methods are required to explore the interconversion rates [583].
The discovery of novel antivirals for the treatment of mpox: is drug repurposing the answer?
Published in Expert Opinion on Drug Discovery, 2023
Ahmed A. Ezat, Jameel M. Abduljalil, Ahmed M. Elghareib, Ahmed Samir, Abdo A. Elfiky
The drug discovery dilemma relies on the time needed to develop potential candidates against newly discovered or reemerged viral breakthroughs [86]. For this reason, millions of people are at risk of deadly and fast-spreading viruses like human coronaviruses, Zika, Ebola, influenza viruses, and many others. Orthopox viruses are one of the reemerging zoonotic disease-causing viruses that attracted our attention recently [87]. In order to face such challenging and deadly viral breakthroughs, we can’t heavily rely on the conventional drug discovery pipeline to find new treatments, although the timeline to develop new drugs against new targets has been shortened due to new computational and experimental advances in the last few decades. We need to find fast and suitable treatment strategies to stop the virus from spreading and save humans. One of these valuable strategies that showed successful results during the recent SARS-CoV-2 breakthrough is drug repurposing. It is usually effective in many emerging or reemerged epidemics and pandemics. We can repurpose drug chemotypes that have safe clinical and pharmacological properties to be used in humans. We can quickly screen the possible binding of such drug compounds against viral targets. Fortunately, advancements in structural biological techniques, such as cryo-electron microscopy (cryo-EM), enabled researchers to study huge massive proteins, protein complexes, and nucleic acid or membrane-associated proteins with impressive high resolution [88].
Electron microscopy overview of SARS-COV2 and its clinical impact
Published in Ultrastructural Pathology, 2022
Soheir Saiid Mansy, Mona Mahmoud AbouSamra
Many techniques, including NMR spectroscopy, X-ray solution scattering, neutron diffraction, various spectroscopic techniques, and X-ray crystallography, have been used to determine the shape and structure of biological molecules. Recently, cryo-electron microscopy has become the most effective tool in structural biology after the technical development of its resolutions, which permits the identification of the biomolecular structure in its natural state.59 Cryo-EM has an advantage over X-ray crystallography, and is the most effective tool in analyzing macromolecules during the last few years. Cryo-EM reveals structures in fast-frozen non-crystalline biological samples that are closer to their natural state at an atomic level. In addition, it requires much smaller macromolecule samples to work with, unlike X-ray crystallography, which needs large pieces of materials to optimize the crystallization conditions.59 Hence, cryo-EM has become the tool of choice for determining the structure of macromolecular complexes, especially supra-assemblies that are difficult to prepare in large quantities or virtually inaccessible to crystallize.59,61,62 Identifying the structural biology of viral protein complexes at molecular resolution is important for designing small drug molecules to bind and impair their function.32
A beacon for broader impact: illuminating science
Published in Journal of Visual Communication in Medicine, 2019
Our time is one of rapid rate of change, especially in science and technology; it is known as the ‘The Digital Age’, ‘The Century of Biology’, and ‘The Information Age’. With new advances in imaging, like cryo-electron microscopy, we have insight into biological structures like never before. With technologies in science, such as CRISPR-Cas9 genome editing, a system adept at knocking out mutations, researchers have opened a new gamut of potential applications in genetics.