March 30, 2020

expert reaction to two structural papers on COVID-19

Two papers, published in Nature, report on the structural biology of COVID-19. 

Prof Jim Naismith FRS FMedSci, Rosalind Franklin Institute and Oxford University, said:

“These two papers, one from China and one from the USA,  are a vivid demonstration of the role structural biology will play in defeating the pandemic.

“The studies describe how the atoms of the viral spike protein bind to the atoms of the human ACE2 protein to make a complex. This complex is key to the virus entering the human cell and starting the infection.

“What is most interesting are the very subtle differences between COVID-19 and SARS in how the atoms in the complex are arranged. These very subtle differences are why the COVID-19 virus binds to the receptor more tightly. These papers are a very important step in understanding why COVID-19 is so dangerous and will help shape the thinking about drugs to stop it. This work highlights the importance of international cooperation in science.”

Dr Zania Stamataki, Viral Immunologist, University of Birmingham, said:

“Solving the structure of virus-receptor interactions helps us understand the mode of action of neutralising antibodies that prevent the virus from binding to its receptor on target cells.

“There are limited data to answer whether anti-viral antibodies in COVID-19 are able to protect against re-infection, but antibodies that prevent the binding of the virus to its receptor on target cells have been previously reported¹.

“A dangerous pro-inflammatory role of antibodies, however, has also previously been identified, where antibodies activated immune cells that can cause collateral damage in the lungs². Encouragingly, combination treatment of anti-inflammatories together with convalescent sera (containing virus-specific antibodies) given to critically ill patients has been previously shown to reduce mortality³. That one was a small, uncontrolled study and further studies in the coming months will be important to shed light on whether virus-specific antibodies are friends or foes in COVID-19.

¹ https://doi.org/10.1101/2020.03.11.987958 and https://doi.org/10.1101/2020.03.21.990770

² Liu et al., JCI Insight 2020

³ Shen et al, JAMA 27^th March 2020

Prof Ian Jones, Professor of Virology, University of Reading, said:

“These are molecular snapshots of the virus making its first contact with the cell, opening the door to infection if you like. It’s the stage at which a vaccine would work, and the data will be useful to fine-tune the vaccines in current development. What’s a bit more sobering is that the speed at which this type of molecular analysis is done far outstrips the pace at which vaccine manufacture can take place, highlighting the urgent need for faster vaccine solutions in the future.”

‘Structural basis of receptor recognition by SARS-CoV-2’ and ‘Structure of the SARS-CoV-2 spike receptor binding domain bound to the ACE2 receptor’ by Jian Shang et al. and Jun Lan et al. were published in Nature at 10am UK time on Monday 30 March.

Declared interests

None received.