Accelerating drug-discovery against COVID-19

Natassa Kantsadi and John Vakonakis evaluate how well small chemical molecules bind to a key enzyme of the new coronavirus causing COVID-19 (

COVID-19 has dramatically impacted all our lives in 2020. Scientists in Oxford have joined forces with groups world-wide to accelerate the discovery of new drugs to combat COVID-19. A ‘COVID Moonshot’ effort (1) envisages developing a drug candidate in just 9 months by crowdsourcing ideas and resources, including test assays and funding, from interested scientists as well as the general public.


vakonakis covid image


Potential drug candidates of ‘COVID Moonshot’ target the main protease enzyme of the new coronavirus, SARS-CoV-2. This protease, known as Mpro, is essential for viral replication in human cells as it processes a single large polypeptide produced by the virus into functional proteins. Mpro-targeting drugs are being developed starting from small chemical ‘fragments’ that bind to Mpro, which were discovered by X-ray crystallography at Diamond Light Source in Oxfordshire (2). However, crystallography does not provide information on how strongly these ‘fragments’ bind to Mpro.

In a new study, published online for accelerated dissemination (3), Natassa Kantsadi and John Vakonakis used nuclear magnetic resonance (NMR) spectroscopy (4) to assess the relative binding strength of chemical ‘fragments’ to Mpro. They discovered that among 39 small chemicals seen to form non-covalent complexes with Mpro in crystals, just four showed relatively strong binding in solution. Two of these four binders targeted the active site of the protease, while the other two bound Mpro sites that may influence protease activity in an allosteric manner. This information will ensure that Mpro-targeting drugs will be designed starting from the best possible starting points. 



  1. COVID Moonshot:
  2. Mpro crystallographic fragment screening:
  3. NMR study of fragment binding in solution:
  4. NMR facility of Oxford Biochemistry:


John Vakonakis
1st July 2020