Blockbuster ZIKV Drug Research Published on Nature, Review of ZIKV Vaccines

Zika virus (ZIKV) spread rapidly worldwide since its outbreak in May 2015 and was listed as a "public health emergency of international concern" by WHO. Research of scientists has made us know deeper about the pathogenic molecular mechanism, virus structure and key pathogenic protein structure of ZIKV, however, there is still no effective drug and vaccine for ZIKV in the world. Next, I will review the ZIKV vaccine pipelines in development in the world by taking the blockbuster ZIKV drug research published on Nature by the Fudan University team as the entry point.

I. The blockbuster ZIKV drug research results published on Nature

There is still no effective drug or vaccine for the treatment of ZIKV disease, and the research projects on the virus prevention have mainly focused on the anti-Zika small molecule or antibody drugs. The Fudan University team led by Jiang Shibo and Lu Lu has recently designed and synthesized a peptide-based viral inactivator that can effectively kill ZIKV. The drug shows effect in mouse model, which is important research progress that has attracted extensive attention of the industry. The team conducted systematic analysis and research on the E protein sequence of ZIKV, and successfully designed the peptide-based candidate drug (Z2) that can inactivate ZIKV and effectively inhibit virus infection: it significantly reduced the ZIKV infection rate of placentas and fetuses in in vivo experiments and blocked the vertical transmission of ZIKV.

II. List of vaccines in development for ZIKV

WHO lifted the emergency of Zika at the end of 2016, however, long-term attention is still needed. With scientists’ research on ZIKV deepened increasingly, research has become increasingly clear about the pathogenic molecular mechanism, molecular structure, and potential drug targets, etc. of the virus, and research on the virus vaccines is also constantly advancing. The relevant virus vaccines are mainly DNA vaccine, recombinant vaccine and inactivated vaccine according to the disclosed information, and details of vaccines in development are summarized into the following table:

III. ZIKV: international public health emergency

According to the 2016 edition of ZIKV disease diagnosis and treatment regimen, Zika virus belongs to Flaviviridae Flavivirus (the dengue virus we know also belongs to Flavivirus), with the genotype divided into Asian and African types; the virus was found in rhesus monkeys in Uganda in 1969, outbroke three 3 times separately in 2007, 2013, and 2015-2016, and the mosquito vector transmission and infection of ZIKV have been reported in about 80 countries or tribes.

Fundamental research on ZIKV is summarized as follows:

1. Pathogenic molecular mechanism of ZIKV: Technicians of a German research team found by using electron microscope and light microscope that ZIKV could rearrange the endoplasmic reticulum and cytoskeletal structure of host cells to form protective cover and promote virus RNA and newly made virions to shuttle back and forth, and produce large amounts of Zika virus.

2. Why ZIKV is closely connected with microcephaly: ZIKV is a self-limited disease itself, however, research showed that the microcephaly might be closely connected with infection of such virus. By building an "early brain" model constituted by neural precursor cells, the team from University of Cologne found that ZIKV could make the differentiation of neural precursor cells abnormal, with a large number of neural precursor cells not participating in the formation of the complete brain, leading to microcephaly.

3. Analysis of key pathogenic protein of ZIKV and drug target: Researchers from Purdue University and National Institutes of Health isolated the virus from an infected patient body, analyzed its structure under 3.8 Å resolution by using the cryo-electron microscopy technique, and found that the virus has a structure similar to those of other Flaviviruses and inferred that the Asn154 glycosylation site of the capsid protein (consisting of 180 copies of the E glycoprotein and M protein) might be associated with the disease treatment.

Researchers from Duke University published another breakthrough research on structure on April 19, 2016, which provides an important thought for research on ZIKV drug, and can be referenced by insiders. (Shi J, Lok S. Structure of the thermally stable Zika virus[J]. Nature, 2016, 533: 19.)

The epidemic situation of ZIKV disease has been controlled, however, the disease is still of global concern. The development of antiviral vaccines and drugs is very crucial. This article makes some summary and interpretation of the latest advances of the current virus research and drug development as well as the vaccine projects in development.

By Tang