Scientists have found structural features in nCoV’s genetic material copying apparatus, laying the foundation for the development of the Covid-19 special drug.
The Chinese team successfully analyzed the three-dimensional structure of RNA-dependent RNA polymerase at subatomic resolution, revealing the structural characteristics of the “main engine” in nCoV’s genetic material copying apparatus. The research was published in the open bioRixv Biological Reserve on March 17.
RNA-dependent polymerase RNA (RdRp or nsp12 for short) is an enzyme that catalyzes RNA replication. When corona viruses start to copy in large numbers, they invade cells, RdRp now plays an important role in the synthesis of RNA, the genetic material of the virus. RdRp is the main target for antiviral drugs, such as Remdesivir, which is being tested in China for its ability to inhibit nCoV.
After collecting and processing nearly 8,000 images from electronic computers, the researchers analyzed the three-dimensional structure of a complex made up of molecular bonds by frozen electronic glass. high prize.
Through image analysis, the team discovered the mechanism of reaction and transport of the group from one substance to another. This is also the first time the team has discovered a β hairpin structure located at the end of RNA polymerase.
The researchers said that this is the first time the internal structure of the nCoV replication apparatus “nsp12-nsp7-nsp8” has been accurately described, providing an important theoretical foundation for in-depth study of molecular mechanisms. operation of nCoV copying apparatus. The research also opens new avenues for the development of anti-Covid-19 specific drugs.
Since February, the China-Japan Friendship Hospital, the Pharmaceutical Institute of the Chinese Academy of Medical Sciences, and some hospitals in Wuhan have been conducting experimental treatments of Remdesivir. However, this process was difficult and interrupted by the lack of patients eligible for drug trials and the lack of information about the nCoV 3D RNA polymerase structure.
Successful analysis of nCoV’s 3D RNA polymerase structure is a step of development and potential for effective therapeutic drugs. Estimated drug test results will be announced by the end of April.
The research was carried out by scientists from the Structural Biology Laboratory of Tsinghua University, the School of Life Sciences, the Shanghai Institute of Advanced Immune Chemistry and the Laboratory of Chemical Biology, University of Nankai University (Tianjin), combined with the Chinese Academy of Sciences and the Center for Space Molecular Research, University of Queensland, Australia.
In the study of scientists collecting and processing 7,994 images from electronic computers, analyzing the three-dimensional structure of a complex made up of nsp12 linked to nsp7 and nsp8, using frozen electronic glass with a resolution of 2.9 angstroms (1 angstrom = 0.1 nanometers).
The structure of RNA polymerase consists of three subdomains, respectively named by the team, “right hand”, “finger”, “palm” and “thumb”, linked to polymerase domain (including nsp7, nsp8- 1, nsp8-2) and the specific domain contains nucleotide transferase (NiRAN). The NiRAN domain is a transport enzyme, performing reactions that transport a group from one substance to another.