When the epidemic of COVID-19 broke out, a joint research team was set up quickly, to enable research work on understanding the virus and accelerate the drug discovery. Led by professors Hualiang Jiang and Zihe Rao, the team is formed by over 20 research groups from SIAIS (Shanghai Institute for Advanced Immunochemical Studies) of ShanghaiTech and Shanghai Institute of Materia Medica (SIMM).
Professors ZiheRao and Haitao Yang’s research team at SIAIS determined the high-resolution crystal structure of SARS-CoV-2 3CL hydrolase (Mpro) within a very short time. Subsequently, the joint team discovered a total of 30 candidate drugs for COVID-19 treatment by combining virtually screening method with enzyme assay testing, in the databases of known FDA approved drugs, natural product as well as their in-house anti-virus compound.
These candidate drugs include (details as shown in the attached Table 1):
12 anti-HIV drugs, such as the protease inhibitors Indinavir, Saquinavir, Lopinavir, Carfizomib, Ritonavir and Remdesivir;
2 anti-respiratory syncytial virus drugs, 1 anti-human-megaphagocyte virus drug, 1 anti-schizophrenia drug, as well as 1 immunosuppressant.
Among of them, those compounds which have the stilbenes group, such as Montelukast, Polydatin and Deoxyrhapontin, show potential inhibitory activities on the virus by targeting Mpro.
Based on the previous anti-SARS research and computational modeling results, Cinanserin and Cyclosporine A present potential inhibitory effects on SARS-CoV-2. Cinanserin was used in the 1970s to treat schizophrenia. The immunosuppressant Cyclosporin A can prevent the combination between nucleocapsid protein of the virus and humancyclosporin A. Previous studies have proved that combination therapy of interferon and Cyclosporin A can significantly inhibit the replication and tissue damage of coronavirus in human bronchi and lungs.
On January 25th, the joint team disclosed their findings of the candidate drugs to the public immediately, to assist clinicians, researchers and other related professionals with the improvement of COVID-19 therapy.
* The cover image is from http://nmdc.cn/#/nCoV