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| Research reveals new strategies for the development of antiviral drugs for RNAi inhibitors |
RNAi is a highly conserved post-transcriptional gene silencing mechanism in eukaryotes, and it is also a highly effective antiviral natural immune mechanism
.
When the virus infects the host cell, the dsRNA produced by viral RNA replication is recognized by Dicer, a key protein in the RNAi pathway, and cut into virus-derived small interfering RNA (vsiRNA).
In 2017, a collaborative study by Zhou Xi's team from Wuhan Institute of Virology, Chinese Academy of Sciences/State Key Laboratory of Virology found that the non-structural protein 3A of enterovirus EV71 has RNAi suppression (VSR) activity, which can prevent Dicer from cutting viral dsRNA and vsiRNA The EV71 mutant virus lacking 3A-VSR activity can produce a large amount of vsiRNA in the infected mammalian cells and in vivo, which stimulates the RNAi antiviral response, thus proving that RNAi as an antiviral immunity still exists in mammals, and Revealed a mechanism by which human viruses escape RNAi immunity (Immunity 2017)
.
In addition, the team also discovered VSR proteins encoded by various important human viruses such as flavivirus (dengue virus, Japanese encephalitis virus, Zika virus, etc.
In this study, the team innovatively proposed a drug development concept that targets VSR to release the antiviral potential of RNAi
.
They took the enterovirus EV71 as the object, and designed several VSR-targeting peptides (VTP) for the key functional regions of the VSR of its 3A protein
This study confirmed for the first time that VTP-specific targeting of VSR can effectively release RNAi antiviral immunity in virus-infected cells and in vivo, which fully proves the physiological and functional importance of RNAi as mammalian antiviral immunity
.
More importantly, from the perspective of antiviral drug development, the research is based on a new antiviral mechanism and found that VSR is a new type of drug target, and developed a first-in-class candidate for the enterovirus VSR mechanism.
The related paper was published online in the international academic journal Immunity ("Immunity") on September 22, 2021.
The paper is entitled "Inhibition of viral suppressor of RNAi proteins by designer peptides protects from enteroviral infection in vivo"
.
Researcher Zhou Xi from Wuhan Institute of Virology/State Key Laboratory of Virology and Researcher Lu Lu from the Ministry of Education/Key Laboratory of Medical Molecular Virology of Fudan University are the co-corresponding authors.
Related paper information: https://doi.
https://doi.
org/10.
1016/j.
immuni.
2021.
08.
027
