Allosteric Inhibitors of the Main Protease of SARS-CoV-2

Case ID:

In this report, the SARS-CoV-2 3CLpro was expressed and purified. By using a FRET-based enzymatic assay, the researchers have screened a library consisting of more than 300 different niclosamide derivatives and identified three molecules JMX0286, JMX0301, and JMX0941 as potent allosteric inhibitors against SARS-CoV-2 3CLpro, with IC50 values like that of known covalent inhibitor boceprevir. In a cell-based antiviral assay, these inhibitors can inhibit the virus growth with EC50 in the range of 2-3 μM. The mechanism of action of JMX0286, JMX0301, and JMX0941 were characterized by enzyme kinetics, affinity binding and protein-based substrate digestion. Molecular docking suggested that JMX0286, JMX0301, JMX0941 bind specifically to an allosteric pocket of the SARS-CoV-2 3CL protease. This study provides three potent compounds for further studies.

The COVID-19 pandemic has led to twin public health and economic crises around the world. Not only has it cost hundreds of thousands of lives but also severely impacted livelihoods and placed enormous strain on community healthcare and welfare services. SARS-CoV-2 has raised the alarm to search for effective therapy for this virus. To date several vaccines have been approved but few available drugs reported recently still need approval from FDA. Remdesivir was approved for emergency use only and most of the medication on the market falls into that category.


  • COVID therapy/treatment
  • Inhibits virus growth


  • Effectiveness
  • Will decrease deaths
  • Scalable
Patent Information:
Contact For More Information:
Garrett Edmunds
Licensing Manager, UAHS-TLA
The University of Arizona
Lead Inventor(s):
Hongmin Li
subodh samrat
Zhong Li
Jia Zhou
Jimin Xu