Search of SARS-CoV-2 Mpro inhibitors according to "Supercomputer Fugaku” in Japan

In Japan, a project to identify therapeutic drug candidate of COVID19 by Supercomputer Fugaku is being carried out (1). In our collaborative research project, using the molecular dynamics (MD) simulation, the search for therapeutic drug candidates that exhibit high affinity to the major protease (Mpro) of SARS-CoV-2 from the existing drugs database has been carried out.

The purpose of this project is to identify therapeutic drug candidates for COVID-19 from 2,128 existing drugs, not limited to antiviral drugs.

In December 2020, some of the analysis results were reported. Molecular dynamics (MD) simulations by Supercomputer Fugaku have identified dozens of promising candidates for the treatment of COVID-19.

Among these candidate drugs, there were 12 drugs that are undergoing clinical research and clinical trials for COVID-19. The results of this project revealed that the parasite anthelmintic Niclosamide has Mpro inhibitory activity. Furthermore, it was clarified that the hepatitis C therapeutic agent nitazoxanide is effective as a therapeutic agent for COVID-19. From results of this project, the target protein of nitazoxanide was revealed to be a SARS-CoV-2 Mpro.

From the results of this project, it was clarified that there are many existing drugs for which the application of treatment to COVID-19 has not yet been considered. Among those existing drugs identified as candidate drugs for COVID-19, there are also drugs licensed by domestic pharmaceutical companies. In the future, our collaborative research project team are planning to discuss clinical research and clinical trials with various research groups.

(1) Joint research between Kyoto University and RIKEN and Kyoto Medical Center

Disclosure of potential conflicts of interest
The authors declare no potential conflicts of interest.

Data availability and Consent to publish
This manuscript is an editorial and does not contain research data. Therefore, there is no research data or information to be published or opened.

Acknowledgments
We thank all the medical staffs and co-medical staffs for providing and helping medical research at National Hospital Organization Kyoto Medical Center and Kyoto University School of Medicine.

Science Published on February 23, 2021. by Kyoto@Takuma H