Currently, the Zika virus epidemic has spread from South America and Latin America to Southeast Asia. There are isolated cases of the Zika virus in Singapore, Malaysia, Thailand and other countries. The virus has become a threat to global public safety, but effective treatment is yet to be developed. A research team led by professor Yang Haitao from Tianjin University and Professor Ji Xiaoyun from Nanjing University has formulated a new breakthrough in the key drug targets. The team analyzed the three-dimensional structure of the NS2B-NS3pro protease replication of the Zika virus at the atomic resolution level. The protease replication plays an important adjusting role in the whole life cycle of the Zika virus. The analysis of the protease replication of the virus has built a foundation on which to develop a specific drug to cure it. The research results have been published online in the academic magazine Cell Research released by the Nature publishing group.

The virus cannot commence the reproduction process until the protease replication is activated and finishes a series of hydrolysis processes. The researchers successfully analyzed the crystalline structure of the NS2B-NS3pro protease replication, which revealed the key molecular mechanism of the activation of the virus protease. One team member, a Ph.D. candidate named Chen Xia from the School of Life Science of Tianjin University explained that, “The NS2B-NS3pro protease replication is like a pair of ‘tiny scissors’. Once it’s activated, it can ‘cut off’ the long-chain protein related to the duplication of the virus. The proteomic ‘tiny unit’ after separation can start the duplication of the virus assembly. What we finally want to achieve is to restrain the protease from being activated and working.” 

Using the protease compound as a target for drug development, scientists have already filtered an effective inhibitor named “aprotinin”. Aprotinin is a clinical drug used in operations to stem bleeding. It has a significant inhibiting effect on the protease of the Zika virus. The discovery of the inhibitor has aided the development of drugs to combat Zika. “There has been success leading cards using protease as drug targets to develop the anti-virus drug, for example, the telaprevir and boceprevir designed drug targeting hcvHCV has come in already”, said Chen Xia. 

It was also discovered during the research that there is a special condition of “self-inhibition”. Following this, scientists came up with a brand new design strategy for anti-virus drugs—design a compound to lock the protease in a ‘condition of self-inhibition’, and then the protease can’t be activated, inhibiting the duplication of the virus. 

According to the data shown by the American Centers for Disease Control and Prevention, the Zika virus has spread to over 60 countries and districts. The Zika virus can cause not only neonatal microcephaly but Guillian Barre syndrome as well. The latter syndrome is a serious nervous system disease, which can lead to paralysis and even death of patients.