Critical Interaction reveals strength of SARS-CoV-2 Protein


Scientists at the Department of Energy’s SLAC National Accelerator Laboratory recently witnessed the moment when a SARS-CoV-2 virus protein Mpro cut a protective protein known as NEMO, in an infected person. Without NEMO, an immune system is slower to respond to increasing viral loads or new infections.


Oak Ridge National Laboratory scientists Dan Jacobson and Erica Prates, near the Summit supercomputer. (Credit: Oak Ridge National Laboratory)


Funnelling powerful x-rays from SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) onto crystallised samples of the protein complex, revealed how Mpro attacks NEMO at the molecular level as it dismantled NEMO’s primary function of helping our immune system communicate.


“We saw that the virus protein cuts through NEMO as easily as sharp scissors through


thin paper,” said co-senior author Soichi Wakatsuki, Professor at SLAC and Stanford. “Imagine the bad things that happen when good proteins in our bodies start getting cut into pieces.”


The images from SSRL showed the exact location of NEMO’s cut and provided the fi rst structure of SARS-CoV-2 Mpro bound to a human protein.


“If you can block the sites where Mpro binds to NEMO, you can stop this cut from happening over and over,” SSRL lead scientist and co-author Irimpan Mathews said. “Stopping Mpro could slow down how fast the virus takes over a body. Solving the crystal structure revealed Mpro’s binding sites and was one of the fi rst steps to stopping the protein.”


NEMO is a critical part of the human immune systems protective infl ammatory response; when cut it helps the virus evade innate immune responses. A separate study by researchers at institutions in Germany found that the loss of NEMO by the action of Mpro could lead to damage in certain brain cells, causing neurological symptoms observed in COVID-19 patients, the researchers said.


“The crystal structures of NEMO and Mpro provide us with the targets to develop treatments that stop these cuts from happening,” SLAC scientist and co-fi rst author Mikhail Ali Hameedi said. “Although current antiviral drugs can target Mpro, seeing the molecular details of how Mpro attacks NEMO will help us develop new treatments in the future as Mpro mutates.”


To predict how well Mpro binds to NEMO, researchers used the Summit supercomputer at the Oak Ridge Leadership Computing Facility, combining molecular dynamics simulations with fi ve machine learning models. Applying quantum chemistry, they found that Mpro likely has the highest binding affi nity in SARS-CoV-2 compared to the other primary coronaviruses.


This image shows how SARS-CoV-2 Mpro recognizes and cuts NEMO based on the crystal structure determined using a powerful X-ray beam at SSRL Beam Line 12-2. (Credit : SLAC National Accelerator Laboratory)


“With a set of computational approaches, we were able to predict the strongest binding spots between NEMO and Mpro,” co-fi rst author and ORNL scientist Erica Prates said. “We think that a high binding affi nity at these hot spots helps explain the high fi tness of the virus in humans.”


Moving forward, the biomedical industry could use the study to help build better inhibitor drugs and understand how other proteins could be affected by Mpro, Wakatsuki said.


“NEMO is only the tip of the iceberg,” he added.. “We can now study what happens when many other proteins in the body are cleaved by Mpro during infection.”


More information online: ilmt.co/PL/Pxw0 Citation: M. A. Hameedi et al., Nature Communications, 8 September 2022 (10.1038/s41467-022-32922-9)


58933pr@reply-direct.com


Microscopy Techniques unveil secret of high-temperature Superconductors


Superconductors that can conduct electricity with zero resistance enabling an electric current can persist indefi nitely, are used in various applications, including MRI scanners and high-speed maglev trains; however superconductivity typically requires extremely low temperatures, limiting their widespread use. A major goal within physics research is to develop super conductors that work at ambient temperatures, which could revolutionise energy transport and storage.


Certain copper oxide materials have demonstrated superconductivity at higher temperatures than conventional superconductors, although the mechanism behind this has remained unknown since their discovery in 1987.


Séamus Davis Credit: University of Oxford


An international team led by Séamus Davis, Professor of Physics at the University of Oxford and University College Cork and involving scientists in Oxford, Cork in Ireland, the


USA, Japan and Germany, have developed two new microscopy techniques to investigate these materials further. The fi rst of these measured the difference in energy between the copper and oxygen atom orbitals, as a function of their location. The second method measured the amplitude of the electron-pair wave function (the strength of the superconductivity) at every oxygen atom and at every copper atom.


“By visualising the strength of the superconductivity as a function of differences between orbital energies, for the fi rst time ever we were able to measure precisely the relationship required to validate or invalidate one of the leading theories of high-temperature superconductivity, at the atomic scale,” said Professor Davis.


As predicted by the theory, the results showed a quantitative, inverse relationship between the charge-transfer energy difference between adjacent oxygen and copper atoms and the strength of the superconductivity.


According to the research team, this discovery could prove a historic step towards developing room- temperature superconductors. Ultimately, these could have far-reaching applications ranging from maglev trains, nuclear fusion reactors, quantum computers, and high-energy particle accelerators, not to mention super-effi cient energy transfer and storage.


Professor Davis added: “This has been one of the Holy Grails of problems in physics research for nearly 40 years. Many people believe that cheap, readily available room-temperature superconductors would be as revolutionary for the human civilization as the introduction of electricity itself.”


The fi ndings were published in PNAS More information online: ilmt.co/PL/G2Mq


58921pr@reply-direct.com


Global Imaging Competition – Entries open


Entries are now open for Evident’s fourth Global Image of the Year Scientifi c Light Microscopy Award, with entries accepted through to 28th February 2023. Each year, the competition recognises the best in scientifi c imaging worldwide. For the fi rst time, the contest welcomes materials science images in addition to life science images to show the versatility of the art of science.


The global prize and three regional prizes will be awarded to the scientifi c images that receive the highest scores. Prizes include an Olympus SZX7 stereo microscope with a DP23 digital camera or X Line™ objectives for the global winner and an Olympus CX23 upright microscope or SZ61 stereo microscope for the regional winners in Asia, Europe and the Americas. An additional prize of an SZ61 stereo microscope will be awarded to the winner of a new dedicated category for materials science and engineering images.


The international jury consists of experts in science and imaging, including Geoff Williams, Manager of the Leduc BioImaging Facility at Brown University; Harini Sreenivasappa, Microscopy Facility Manager of the Cell Imaging Center at Drexel University; Rachid Rezgui, Research Instrumentation Scientist at New York University Abu Dhabi; Urs Ziegler, Managing Director of the Center for Microscopy and Image Analysis at the University of Zurich; Yujie Sun, tenured Professor and Boya distinguished Professor of Peking University; and Sarah Ellis, Head of the Centre for Imaging the Tumour Environment (CITE) at the Olivia Newton-John Cancer Research Institute in Australia.


Jan Martinek from the Czech Republic was selected as the 2021 global winner for a glowing image of an Arabidopsis thaliana flower with pollen tubes growing through the pistil. The flower tissues were chemically cleared to reveal the pollen tubes stained with aniline blue (yellow fluorescence). Martinek chose to image this flower to highlight the beauty of science in plant cell research.


All entries will be evaluated based on artistic and visual aspects, scientifi c impact and microscope profi ciency.


A subsidiary of Olympus, Evident’s IOTY Award began in 2017 as the Image of the Year European Life Science Light Microscopy Award with the aim to celebrate both the artistic and scientifi c value of microscopy images. Today, the competition stays true to this mission by encouraging people around the world to look at scientifi c images in a new way, appreciate their beauty, and share images with others.


Contestants may enter by uploading up to three images, with a description of the equipment used; Winners will be selected by a jury and announced in summer 2023


More information online: ilmt.co/PL/Aw3x 58938pr@reply-direct.com


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72