Crystallography Reviews is publishing a series of articles on the structural biology of the structurally known SARS-CoV-2 proteins by the team of Andrea Thorn at the University of Hamburg, Germany. The eighth paper in the series can be found in this issue. A few more articles on these virus proteins are due in future issues. In October 2023, Katalin Karikó's autobiography was published. In the same month, Katalin Karikó and Drew Weissman were jointly awarded the Nobel Prize in Physiology or Medicine for their understanding of how mRNA interacts with our immune system. This led to the development of a revolutionary vaccine technology which enabled the expeditious response to the COVID-19 pandemic caused by SARS-CoV-2 virus. Now, it is a pleasure to offer my own review of the book. I think we can all get an insight into Karikó's career from its beginnings to her arrival at the gate of the Nobel Prize. So, overall, Issue 4 of Volume 29 of Crystallography Reviews presents both the COVID-19 pandemic’s science and the COVID-19 pandemic scientist working at a fundamental science level: a review on the research results about the structure of a segment of the virus is offered along with the book review on the autobiography of a scientist who has dedicated her life to mRNA research testifying her commitment and perseverance. We also have a general to all fields of crystallography educational review on space groups by Bill Clegg of Newcastle University, UK.
Now to describe some details. Sam Horrell from Diamond Light Source, UK, Sam Martino and Dénes Berta from University College London, UK, Gianluca Santoni from the European Synchrotron Radiation Facility, France, and Ferdinand Kirsten and Andrea Thorn from the University of Hamburg, Germany report on a multifunctional, highly conserved, 67 kDa protein with the title ‘What a Twist: Structural biology of the SARS-CoV-2 Helicase nsp13’. The protein consists of 601 amino acids that folds into five distinct domains. It belongs to the helicase superfamily 1B, which can unwind DNA and RNA in a nucleoside triphosphate dependent manner. A total of 72 structures of SARS-CoV-2 nsp13 have been published in the protein databank (PDB), and reviewed in this article, 56 of which were solved by X-ray crystallography and 16 by single particle cryo electron microscopy. The structures of SARS-CoV-1 and MERS-CoV nsp13 were also available for comparison. This protein is essential to the viral infection cycle, acting as a standalone enzyme. It makes this SARS-CoV-2 helicase a promising target for structure-based drug design. This review summarizes the current structural and functional knowledge of SARS-CoV-2 nsp13 and related helicases, as well as the efforts in structure-based drug design made to date.
The determination and interpretation of the crystal structures require an understanding of the space groups and crystal symmetries. William Clegg’s tutorial review (Newcastle University, UK) ‘Space groups – the final frontier: a tutorial guided tour of some entries in International Tables for Crystallography Volume A’ begins with a brief account of some fundamental principles, provides definitions, and explains some important terminology and notation. His review article explains the design, layout, and contents of the space group representations that make up the main bulk of the International Tables for Crystallography, Volume A, current sixth edition. Three particular space group examples are selected to demonstrate the information given for each space-group type. The determination of the space group and its symmetries of a newly investigated crystalline material is often left to automatic algorithms of crystallographic software based on its measured diffraction pattern. While these automatic procedures generally work reliably, competence and experience is required when dealing with structures that exhibit pseudosymmetry, twinning and potential disordering. This review can assist in comprehending these challenges.
The development of new drugs with potential therapeutic applications is a challenging and complex process. The activity of a drug is the result of a multitude of factors such as bioavailability, toxicity and metabolism. Rational drug design has been a utopia for centuries. It has become feasible by the impressive technological advances in the areas of structural characterization of biomolecules and computer sciences. The book ‘Computational drug discovery and design’ edited by M. Gore and U. B. Jagtap, New York, Humana Press, Springer Science + Business Media, LLC, part of Springer Nature, 2024, is reviewed by Mutia Anika and Yogy Satria Ariyanto from IPB University, Bogor, Indonesia. The book serves as a comprehensive guide in this emerging field. It explores various aspects, ranging from computer aided drug discovery to the application of artificial intelligence in the prediction of absorption, distribution, metabolism, and excretion properties. The book offers invaluable insights into pharmaceutical research, emphasizing the crucial role of crystallography in combination with computational methods. According to the reviewers, it ‘illuminates the path to a future where cutting-edge computational techniques, crystallography, and artificial intelligence converge to revolutionize drug discovery’.
Getting to know the person behind an outstanding scientific achievement is always very exciting. It is particularly interesting when the book is an autobiography. When I read Katalin Karikó's fascinating book ‘Breaking Through, My Life in Science’, New York, Crown, a division of Penguin Random House LLC, 2023, I immediately decided to write a review of the book for Crystallography Reviews to draw attention to it. With the exception of ‘An Extremely Brief Interlude on Science’ of biochemistry, which is important for non-professionals to understand, the main question throughout her book is how the research performed affects the life of the scientist and how the life of the scientist affects the science performed. Her mRNA research had a significant impact on her and her family’s life including moving to different countries, raising a child to become responsible and independent quickly, and spending time away from the most beloved ones. In reverse, her perseverance and family support needed to overcome so many difficulties, there were several occasions when she could have given it up. Her lifetime determination was instrumental in the development of the COVID vaccine, which came just in time to save humankind. Karikó explains the difference between basic science and applied research. She writes about the competitive nature of academic research and skills that has much or little to do with science. She discusses the issue of funding, and how to get important but often overlooked work supported. She provides clear messages on improving academic research, measuring scientific achievement, and the influence of money on academic research with its implications. She shares her vision for the next decade, which will see an explosion of new mRNA therapies and vaccines. She closes her autobiography – which was published after decades of work in the shade, at the time when appreciations were still arriving, – ‘I never dreamed any of this. … But for now, I want to savour this moment just a while longer’. But the last sentence brings us back to the real life of a scientist: ‘There is so much more to discover’.
As ever we welcome new ideas for review articles, and for suggestions regarding books to be reviewed. Please contact me at the e-mail address below. I look forward to welcoming your submissions.