Study reveals coronavirus main protease catalytic mechanism

Recently, Shang Luqing, an associate professor at Nankai University's School of Pharmacy, published a paper in the American Chemical Society's Catalysis, which revealed the catalytic mechanism of the coronavirus main protease, and discussed the differences between the coronavirus MERS-CoV and the SARS-CoV main protease in the catalytic process, thus optimizing the biological activity of the main protease inhibitorsThis work provides the basis for future research on the mutation of the coronavirus, which aims to help develop new coronavirus drugsthere is no clinical drug for the treatment of new coronal pneumonia, Shang Luqing said, through the study of the universal mechanism of the key protein of coronavirus, the development of antiviral drugs is extremely importantin the life activities of coronavirus, its main protease can effectively cut the protein precursor of the virus, and then produce the functional protein of the virus, which is very important for life activities such as the replication of coronavirusTherefore, the main protease is an important target for the research of anti-coronavirus drugs" At this stage, the research on this protease focuses mainly on the study of the specificity of the substrate and the research of dipolymerization, however, the lack of systematic research on its catalytic mechanism restricts the development of the corresponding antiviral drugsTherefore, the catalytic mechanism of the coronavirus main protease can be better designed and discovered as a main protease inhibitor, thus accelerating the development of antiviral drugsShan Luqing saidBased on the crystal structure of MERS-CoV and SARS-CoV main protease, theteam constructed the enzyme activity analysis system, determined the catalytic activity center of the protease, and then carried out the corresponding subject studyThe researchers conducted an in-depth study of the catalytic mechanisms of the MERS-CoV and SARS-CoV main protease identification and enzymatic cutting phasesduring the identification phase, the team explained why the protease's S1 pocket identifies the highly conservative Gln of the substrateDuring the catalytic phase, the team studied how the substrate was fixed by protease and clarified the presence of an important negative power center in proteaseIn addition, the team explored the catalytic differences between MERS-CoV and SARS-CoV main proteasesbased on the above research on catalytic mechanism, the research team optimized the structure of protease inhibitors, effectively improved the activity of inhibitors, and also found potential structural inhibitorsites, which provided a new way of thinking for the development of antiviral drugs targeted at proteases, the team sequenced and overlapped the main proteases of the new coronavirus with the proteases of the previously reported coronavirus, and found that the sites studied were conservatively present in the main proteases of the new coronavirus and several known coronaviruses", "this suggests that the mechanism starring in our study may be a generic mechanism for the main protease of coronavirus, which is important for the development of broad-spectrum antiviral drugs in response to the current and future outbreak of coronaviruses." Shan Luqing said (
Bio valley Bioon.com)