Rao Zihe and Yang Haitao at the Shanghai Institute for Advanced Immunochemical Studies of ShanghaiTech University, together with their collaborators, have been searching for drugs to combat the novel coronavirus, which has claimed over 85,000 lives and infected over 1.4 million people worldwide as of Thursday, according to data published by the World Health Organization.

The Mpro, which plays a pivotal role in mediating viral replication and transcription, is an attractive drug target for this virus.

The team identified a mechanism-based inhibitor, N3, by computer-aided drug design and subsequently determined the crystal structure of the COVID-19 virus Mpro in complex with this compound on Jan. 26, which is the first determined public-domain 3D structure from the COVID-19 virus.

After assaying over 10,000 compounds including approved drugs, drug candidates in clinical trials, and other pharmacologically active compounds as inhibitors of Mpro, several were found to inhibit Mpro, including Disulfiram, Carmofur, Ebselen, Shikonin, Tideglusib and PX-12. Ebselen and N3 both exhibited promising antiviral activity in cell-based assays.

In order to facilitate global researchers to develop antiviral drugs targeting N3 the first time, the joint team disclosed the list of candidate drugs and the structure of the COVID-19 virus Mpro to the public on Jan. 25 and Jan. 26 respectively in advance.

Rao and Yang have been engaged in the research against coronavirus for years since SARS (severe acute respiratory syndrome) broke out in 2003. They determined the crystal structure of the main protease from the SARS virus and discovered inhibitors for coronavirus.