G-quadruplex binder pyridostatin as an effective multi-target ZIKV inhibitor
| Autor: | Chun-Qiong Zhou, Shuwen Liu, Meng-Jia Zhang, Jun-Hui Li, Pei-Dan You, Jun-Tao Huang, Jingyan Li, Min Zou |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
Pyridostatin G-quadruplex Antiviral Agents Biochemistry Virus Viral Proteins Multi target Structural Biology Chlorocebus aethiops medicine Animals heterocyclic compounds RNA Messenger Picolinic Acids Cytotoxicity Vero Cells Molecular Biology Messenger RNA Protease Chemistry food and beverages RNA Zika Virus General Medicine Virology G-Quadruplexes Kinetics Aminoquinolines RNA Viral Thermodynamics Peptide Hydrolases |
| Zdroj: | International Journal of Biological Macromolecules. 190:178-188 |
| ISSN: | 0141-8130 |
| Popis: | At present, there are still no anti-Zika virus (ZIKV) drugs or vaccines approved by FDA with accurate targets and antiviral mechanisms. Considering the RNA G-quadruplex sequences in ZIKV genome, it is very meaningful to develop G-quadruplex binders as potential anti-ZIKV drugs with novel and accurate targets. In this paper, five classical G-quadruplex binders including Ber, Braco 19, NiL, 360A and PDS have been chosen to discuss their interaction with ZIKV RNA G-quadruplexes. PDS shows higher binding affinity and thermal stability than the other G-quadruplex binders. This property is further evidenced in cells by immunofluorescence microscopy. And PDS shows higher anti-ZIKV activity (EC50 = 4.2 ± 0.4 μM) than the other G-quadruplex binders as well as the positive control ribavirin, with a low cytotoxicity. By time-of-addition assay, PDS exerts antiviral activity at the post-entry process of ZIKV replication cycle, thus inhibiting ZIKV mRNA replication and protein expression. Furthermore, PDS combines with ZIKV NS2B-NS3 protease and reduces its catalytic activity. This study suggests that G-quadruplex binder PDS is an effective multi-target ZIKV inhibitor, which provides more guidance to design some novel anti-ZIKV drugs targeting ZIKV RNA G-quadruplexes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect