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The team analyzed the three-dimensional structure of the atomic resolution level of the Zika virus NS2B-NS3pro protease complex. This protease complex plays a key regulatory role in the whole life cycle of Zika virus. The analysis of this protease complex structure lays an important structural foundation for the development of special drugs for the treatment of Zika virus.
The study found that the NS2B-NS3pro protease complex of Zika virus is a key antiviral drug target. Because only the protease complex is activated and a series of hydrolysis reactions are completed, the virus can initiate the replication process. The researchers successfully analyzed the crystal structure of Zika virus NS2B-NS3pro protease complex and revealed the key molecular mechanism of viral protease activation.
"The NS2B-NS3pro protease complex is like a 'small scissors'. When it is activated, it will 'cut' a long-chain protein related to viral replication, and the separated multiple protein 'small units' will be assembled. Start the replication of the virus." Research team member, Chen Xia, a doctoral student at the School of Life Sciences at Tianjin University, said, "What we finally want to achieve is to inhibit the protease and prevent it from being activated and functioning."
Using this protease complex as a drug target, scientists have successfully screened a potent inhibitor called "aprotinin". "Aprotinin" is a clinical drug that is used to stop bleeding during surgery. It has a good inhibitory effect on Zika virus protease activity, and the discovery of this inhibitor will help to further develop anti-Zika virus drugs.
Chen Xia said that there have been successful precedents for the development of antiviral drugs using protease complexes as drug targets. For example, the drugs designed for the protease structure of hepatitis C virus, telaprevir and boceipide, are already on the market.
In addition, the study also found that Zika virus protease has a special "self-inhibition" state. Based on this, scientists have proposed a new antiviral drug design strategy - if a compound can be designed to lock the viral protease in a "self-inhibiting state", the enzyme will not be activated, and ultimately inhibit viral replication. the goal of.
According to the latest data from the US Centers for Disease Control and Prevention, the Zika virus has spread to more than 60 countries and regions. In addition to causing neonatal microcephaly, Zika virus infection can also cause Guillain-Barré syndrome. The latter is a serious neurological disease that can lead to paralysis and even death.
Chinese scientists unveil the mystery of Zika virus protease "self-inhibition"
[China Pharmaceutical Network Technology News] At present, the Zika virus epidemic is more serious, and a global public security has become a serious threat. Recently, the research team led by Yang Haitao of Tianjin University and Ji Xiaoyun, a professor at Nanjing University, made an important breakthrough in revealing the key drug targets of Zika virus, revealing the mystery of the self-inhibition of the viral protease. Relevant research results have been published online in the academic journal Cell Research.
(Chinese scientists unveiled the self-inhibition of Zika virus protease. Source: Baidu Pictures)