Could structural elucidation help support scientists in the pandemic scenarios we are facing today? Dr. Gustavo Santiso-Quinones, Chief Scientific Officer at Eldico Scientific, explains how.
Dr. Santiso-Quinones, the whole world is waiting for scientists to find a cure or a vaccine for COVID-19. You wrote in a recent paper that structural elucidation could play an important role in this challenge. Why is this the case?
Any chemical molecule or biological entity able to cause a defect in the human body, such as a disease, has a certain three-dimensional structure. Understanding this structure is essential. To effectively fight the disease, we need an exact understanding of the detailed structures of the molecules, then we need to find another “good” molecule that perfectly fits into our proteins and thus inhibits the impact of the “bad” molecule — like that of a virus, for example. This is also how many drugs are being screened that work against viruses. Structural elucidation, which is an experiment exploring the atomic structure of molecules, allows scientists to know the exact 3D molecular structure of any virus and the possible active sites in our body where it could interact. By knowing these structural details, scientists are able to faster develop or find drugs (inhibitors) that could help combat a pandemic disease, like the current COVID-19.
What exactly is the advantage of knowing the exact molecular structure of a virus like SARS-CoV2?
Generally speaking, the more information that the scientific community has on the molecular structure of a virus, the better and faster they can identify any possible vaccine(s) or cure(s). There are already many substances on the market, some of which may be applicable to new diseases they were not initially invented for. So, most importantly, knowing the structural properties of the virus leads to the possibility of screening “old” drugs for “new” diseases. For example, by knowing the structure, scientists can perform in silico screening — i.e. via computer simulation — of known drug substances that have been approved and released, and thus identify the potential candidates. This is a great advantage, as the number of clinical trials is reduced, the side effects and risk are known, and the identification process is very fast. By utilizing the knowledge that already exists about these drugs, scientists can save many years of research, clinical trials and the process of approval for a new drug and thus considerably accelerate the journey toward a cure or vaccine.
One of the important factors in finding a vaccine during a global pandemic is time. What are the challenges scientists face in this race against time?
Structural elucidation is extremely important. Currently, these experiments either require a sophisticated synchrotron beam line — of which there are only a few world-wide and only one in Switzerland, located at the Paul Scherrer Institute — or they need a very expensive cryo-EM device, which is mainly an electron microscope. Unfortunately, all these high-end experiments are neither affordable for most of the scientific community nor even easily accessible, drastically limiting the number of experiments and forcing scientists around the world to wait and rely on the data from researchers who have access to the resources needed.
How could the scientific community improve the speed of this research process? How could they reduce costs and increase the number of experiments?
We at ELDICO believe the solution lies in electron diffraction (ED). Imagine that every research facility had access to an in-house device, capable of producing a structure as accurate and fast as a synchrotron experiment, avoiding the trouble of obtaining “big” crystals. If scientists could gain structural information faster, the search for a cure could be accelerated. Let me explain this with a recent example, the Zika virus: once the structure of the virus was known and the structural interaction with human proteins was identified, an existing, commercially available drug was found to be a cure. Its release in just some 12 to 15 months of work — instead of many years of research, clinical trials and the approval, for example, of a new candidate — made the difference.
At present, however, ED experiments are not easy to conduct, and the technology is not straightforward to use. We at ELDICO are developing a dedicated electron diffractometer for nano-crystallographic research. Our device will make structural elucidation easier and faster. The next time such a virus arises, the device will help ensure humanity is better prepared to tackle the molecular structure of the virus faster and able to counter a pandemic much more rapidly.
More Scientific Content from ELDICO:
What are Electron Diffraction and Nanocrystallography and why are they important? (White Paper) --- Rapid Structure Determination of Microcrystalline Molecular Compounds Using Electron Diffraction (Peer-Reviewed Paper) --- Can Electron Diffraction distinguish between carbon and nitrogen atoms? (Application Note).