Novel approach to a rapid cure for COVID-19, supported by ED

The Covid-19 crisis seems to never end, with a potential second lockdown in sight and infection rates on the rise. The world needs a rapid solution, and while a vaccine seems the most promising way out from the present situation, it can prove to be a complicated and long process. Take for example HIV – studied for over 30 years without discovering an effective vaccine, instead, with the help of small molecule drugs, living with the virus becomes attainable.

Indeed, small molecules (having only a few dozen of atoms, as opposed to the ‘large’ ones with hundreds or thousands of atoms) are a good alternative in research, since they already account for approximately 90% of today’s drugs. This is an incredible thing, given that it is such a diverse group of compounds that share nothing in common^[1]. What’s more, small molecules are affordable and even nature is regulating and inhibiting its processes inside us this way. However, designing and making new small molecule drugs is also quite a long and tedious process.

So, what is the way out? Fragment-based drug discovery (FBDD, also fragment-based lead discovery, FBLD) as Daniel Erlanson elucidates in “Many small steps towards a COVID-19 drug” ^[2] definitely is one of the most promising ones. Instead of screening hundreds of thousands of large drugs, FBDD uses limited libraries of existing fragments to find more efficiently the most attractive starting points for medicinal chemistry. This major trend in drug development accounts for nearly 50 FBDD-derived drugs that have presently entered clinical development. In order to guarantee the success of FBDD, fragments need to have been characterised down to their atomic level, as typically done with X-ray diffraction, particularly for computational fragment-based approaches, to further improve the identification of fragment hits^[3]. 

Nonetheless, in order to avoid the time-delimiting step of crystallisation towards sizes in the hundreds of micrometres, it is preferred to change from X-rays to electrons, allowing powders with crystallites in the range of 10 – 100 nanometres to be fully characterised by determining their molecular structure. 

Given ELDICO’s advocacy for ED, I’m convinced that with the timely release of a dedicated electron diffractometer, this innovative instrument will greatly contribute to FBDD for rapid development of drugs against viruses, in our present case, COVID-19. Being by far more cost efficient, significantly faster and delivering better quality results than approaches mostly based on existing “retrofitted” transmission electron microscopes (TEMs), ELDICO’s instrumentation is superior. I am looking forward to see it support a faster than ever drug development.

References:

[1] Xconomy, 2015/11/23 – Small Molecules: The Silent Majority of Pharmaceutical Pipelines

[2] Nature Communication 11, 5048 (2020). https://doi.org/10.1038/s41467-020-18710-3

[3] Drug Discovery Today Volume 25, Issue 9, September 2020, Pages 1693-1701 – The rise of molecular simulations in fragment-based drug design (FBDD): an overview