- 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

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. 


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. 

Structural Analysis of the Main Protease of Multiple Coronaviruses

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

Santa Clara University

Coronavirus 3C-like proteases are the enzymes on the virus that play a key role in viral replication. Coronaviral protease inhibitors could theoretically prevent the virus from initially infecting the host cell, and appear to be promising drug targets. 

Types:
- GC376
- C-Phycoyanin
- peptidomimetic α-ketoamides 

Using Coronaviral Protease Inhibitors to Treat or Prevent COVID-19

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 

Important Values to Define when Discussing Protease Inhibitors

An in-silico study was performed to assess the effectiveness of C-phycoyanin, a compound in spirulina, to inhibit nsp12, a molecule that is required for replication of SARS-CoV-2. 

Study Investigating the Effectiveness of  C-Phycoyanin as a Coronaviral Protease Inhibitor

A structure-based design study observed 11 different alpha-ketoamide protease inhibitors on the Nsp5, 3C- like main protease in coronaviruses and the 3C main protease in enteroviruses. These are the enzymes that are required for protein processing in viruses. 

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