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“What could Leonardo Da Vinci’s Gioconda, the memory of a cellphone, and SARS-CoV-2 have in common? The answer is in a powerful light beam or the so-called synchrotron light, a particle accelerator that allows seeing molecular structures thus providing useful tools in several areas, such as the analysis of works of art, the development of new materials for more data storage and the study of viruses. This last research area is especially relevant in a moment when what is needed to leave the darkness caused by the pandemic is, precisely, light, in the widest sense of the word.
Doctor Gerardo Herrera, a Mexican particle physicist who collaborates at the A Large Ion Collider Experiment (ALICE), one of the four most important experiments of the Large Hadron Collider in Geneva, Switzerland, explains that a synchrotron is a machine that is used to accelerate subatomic particles such as electrons. For Herrera, who is also a science disseminator, it is easy to understand its functions for they are not particularly “exotic” particles, they are the ones that go every day through the light bulbs that illuminate our house to provide us with light or the ones that make a blender’s blades spin. The particles in charge of electricity, electrons, can be accelerated through electric and magnetic fields so that they increasingly acquire speed. In order for those pulses to work, they have to be synchronized with the electron, hence the name synchrotron.
“These machines are currently built in a circular way, that is, they are rings with diameters that go from 80 to 100 meters. Electrons circulate in the circuit and increase their speed in a synchronized way. Every time they reach a curve in the circular path, they emit light, which are basically X-rays, the same ones we use for medical purposes, but when they are transmitted by electrons at these circular machines, they are called synchrotron light ,” says Herrera.
These high-intensity beams are special to observe molecular structures, such as proteins, for instance. “You can see enzymes, amino acids, molecules that enter into the cell’s chemical reactions. With the synchrotron light, you can determine the position of the atoms and obtains a tridimensional map of their structure,” Therefore, this light is very useful to study with detail the processes through which viruses interact with cells and the way in which they react.
The power of light
It was with the help of a synchrotron that a fundamental drug against the H1N1 pandemic was developed: oseltamivir, a selective antiviral prodrug (a biologically inactive substance that is metabolized in the organism into an active substance) against the flu virus. Currently, it is produced by Hoffmann-La Roche under the name Tamiflu and Procaps.
Herrera says it was in the same particle accelerator , the Stanford Linear Accelerator (SLAC), where the existence of quarks was detected 50 years ago, and 30 years later, the fundamental prodrug to fight the 2009 pandemic was created. Physics has worked as a bridge for breakthroughs in different fields of knowledge.
The story goes on. 20 years later, physicists at a China laboratory used the synchrotron light to determine the molecular structure of the SARS-CoV-2 virus. Using the facilities of the Shanghai Synchrotron (SSRF), Zihe Rao from the University of ShanghaiTech, along with his colleague Haitao Yang, was able to decipher the structure of the main protease in SARS-CoV-2 with a covalent inhibitor. Moreover, they made the information publicly available for free at the Protein Data Bank, a global database about the tridimensional structure of proteins and nucleic acids.
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The efforts to completely unmask the enemy and find an effective drug continue with the help of particle accelerators . The Diamond Light Source, a synchrotron located at the Campus of Science and Innovation at Harwell, Oxfordshire in Great Britain, received, since the beginning of the pandemic, over 3,500 models of molecular design to prove an antiviral compound to face COVID-19 . The challenge is not only to find an effective one but for it to be safe and easy to produce. The experiments performed since the beginning of the pandemic have contributed to the global efforts to better understand and combat the origin of the pandemic.
Integrated knowledge
Hence, PostEra Inc. A biotechnology company specialized in the automatic learning for drug development, leads an international team of scientists of the academy and the industry that have gathered to créate a new and innovative non-profit initiative: Covid Moonshot. Their objective is to develop a clinically effective antiviral as soon as possible.
Data generated by Diamond are about new chemical inhibitors that come from all over the world are being analyzed in record time. Researchers worldwide keep sending their designs so that the most promising compounds can be synthesized and tried to determine their antiviral activity and their toxicity. By the end of April, they had already experimentally confirmed 60 possibilities to prove, with effectiveness, a key protein linked to the new coronavirus.
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There are many Mexican scientists working with experiments in particle accelerators throughout the world, such as the case of Herrera who has been working for over 25 years at the Large Hadron Collider in Switzerland, where the Higgs boson was discovered and where scientists are studying the early origin of the universe. It is a large particle accelerator that accelerates protons instead of electrons.
Since the 90s, different groups of physicists have sought the idea of building a synchrotron in Mexico, but Herrera mentions that the plan has been to no avail for many years. The last proposal seemed to resonate with the Hidalgo government but, according to Herrera, there are still no solid plans. “Having a light source with these characteristics allows us not only to study biological molecules but also, for instance, to study oil, the structure it has when it is found in wells at very high pressure and with very high temperatures.” That is how, in addition to its use for drug development, studies with synchrotron radiation can be used to study and extract, in a more efficient way, not only oil but also water. “Synchrotron light can be used for many kinds of research, that’s why they are so coveted. In addition to the U.S., the most developed countries in Europe and Asia have this kind of accelerator.”
For Herrera, it is very important to stress the relationship of physics with COVID-19 because knowledge has been integrated and this area’s impact is fundamental for everything related to technological development.
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