Find the 'key' that maintains nCoV's ability to copy

The researchers found that an enzyme group capable of cutting molecular bonds in nCoV helped find drugs that inhibit their replication ability.

The Chinese team found and successfully analyzed the high-resolution 3D spatial structure of protease Mpro (hydrolytic enzyme group capable of cutting molecular bonds), which is one of the main goals to be defeated. during inhibition of nCoV. Thanks to this, the group synthesized four drugs that are resistant to this protease.

Find the key to maintain the ability to copy nCoV

Professor Haitao Yang, a researcher on the mechanism of interaction between virus and host, a member of the research team, said that nCoV is very devious virus, after invading host cells, this virus immediately Using in-cell materials to synthesize two super-long polypeptide chains (pp1a and pp1ab), necessary for nCoV replication.

These two polypeptide chains are cut into parts (like RNA polymerase synthesized from RNA). These parts are assembled into a "giant" copying mechanism, after which nCoV can start activating copying of its own genetic material. In order for these two polypeptide chains to produce perfectly precise cuts, supporting duplication of materials, nCoV had to synthesize and create a "scissors itself", which is protease Mpro.

Mpro is in charge of the 11 cleavage sites of the two polypeptide chains, only when these sites are correctly cleaved, can the nCoV replication machine function properly.

Because protease Mpro plays an important role in virus replication, and no protease can replace Mpro with the same function. Therefore, Mpro became the main target of nCoV inhibitors.

To address this problem, the team continues to use large-scale virtual screening and screening techniques to select more than 10,000 drugs today and find some with significant inhibitory effects on this main protease. , including carmofur (anticancer compound), ebselen (medicine for hearing disorders), shikonin (antiviral compound) and PX-12 (cancer medicine). In it ebselen significantly inhibits the replication of nCoV at the cellular level.

"The above findings are an encouraging signal in the screening process of drugs that inhibit nCoV, support the development of drugs and vaccines," Professor Haitao Yang said.

The study was published in the April 9 issue of Nature by the team of the Laboratory of Structural Biology, Tsinghua University and the Institute of Medicinal Materials, Chinese Academy of Sciences, in conjunction with the Key Laboratory. about the Special Pathogen, Wuhan Institute of Virology.