Mapping Hydrogen Atoms in SARS-CoV-2 Main Protease

December 1, 2020
Mapping Hydrogen Atoms in SARS-CoV-2 Main Protease
The image shows the SARS-CoV-2 main protease crystal used in the neutron diffraction experiment (left), the enzyme molecule in cartoon representation with transparent surface (center), and a zoomed in area on the catalytic site (right), illustrating the negatively and positively charged residues.

Scientific Achievement

The positions of hydrogen atoms have been located enabling a full determination of the hydrogen bonding and protonation states of the main protease (3CL Mpro) of SARS-CoV-2.

Significance and Impact

Inhibiting 3CL Mpro prevents the virus from replicating, and understanding its structure is an important step in designing new drugs to combat SARS-CoV-2.

Research Details

  • Single crystals of 3CL Mpro were grown, enabling diffraction studies.
  • The full  structure was determined by jointly refining x-ray and neutron diffraction data. 
  • The neutron data allowed for visualization of the protonation states and hydrogen bonding.

“Unusual zwitterionic catalytic site of SARS-CoV-2 main protease revealed by neutron crystallography”
Daniel Kneller, Gwyndalyn Phillips, Kevin Weiss, Swati Pant, Qiu Zhang, Hugh O’Neill Leighton Coates, and Andrey Kovalevsky,
Journal of Biological Chemistry, (2020).