The structure of the main protease of SARS-CoV-2 was found to be very similar to the main protease of SARS-CoV-1. The two proteases share 96.08% sequence identity. 


Santa Clara University

Wang and colleagues used differential scanning fluorimetry to look at the binding affinity of GC376 and other main protease inhibitors to SARS-CoV-2.

Study Investigating the Effectiveness of GC376 as a Coronaviral Protease Inhibitor

Wang, Y., Yang W., Chen Y. et al.(2020 Aug 1). Structural basis of SARS-CoV-2 main protease inhibition by a broad spectrum anti-coronaviral drug. American Journal of Cancer Research, 10(8): 2535-2545. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471349/pdf/ajcr0010-2535.pdf	


Structural basis of SARS-CoV-2 main protease inhibition by a broad spectrum anti-coronaviral drug 

- Studies have demonstrated the ability of GC376 to prevent the proliferation of multiple human and animal coronaviruses.

The coronaviruses it has shown to prevent the proliferation of are:
- MERS-CoV
- SARS-CoV-1
- porcine epidemic diarrhea virus (PEDV)
- feline infectious peritonitis virus (FIPV)


GC376 Prevents the Proliferation of Multiple Coronaviruses

- The Kd value of GC376 to the main protease of SARS-CoV-2 is 1.6uM. This value was determined by isothermal titration calorimetry.

Binding affinity of GC376 to SARS-CoV-2

- To determine how effective GC376 is at inhibiting the activity of the main protease of SARS-CoV-2, a fluorescence resolution energy transfer assay with a fluorescence protein substrate was used. It was found that GC376 has a potent ability to inhibit the activity of SARS-CoV-2 main protease, with a half-maximal inhibitory concentration of 0.89uM. 

The inhibition efficiency of GC376 on SARS-CoV-2

Structural Analysis of the Main Protease of SARS-CoV-2

The structure of the main proteases of the coronaviruses from this study were all very similar. Wang and colleagues suggest that GC376 may be very adaptable to inhibit the main proteases of all coronaviruses since the structures of their main proteases are very similar. 

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