Brevinin-2GHk, a Peptide Derived from the Skin of Fejervarya limnocharis, Inhibits Zika Virus Infection by Disrupting Viral Integrity

Abstract

Several years have passed since the Zika virus (ZIKV) pandemic reoccurred in 2015–2016. However, there is still a lack of proved protective vaccines or effective drugs against ZIKV. The peptide brevinin-2GHk (BR2GK), pertaining to the brevinin-2 family of antimicrobial peptides, has been reported to exhibit only weak antibacterial activity, and its antiviral effects have not been investigated. Thus, we analyzed the effect of BR2GK on ZIKV infection. BR2GK showed significant inhibitory activity in the early and middle stages of ZIKV infection, with negligible cytotoxicity. Furthermore, BR2GK was suggested to bind with ZIKV E protein and disrupt the integrity of the envelope, thus directly inactivating ZIKV. In addition, BR2GK can also penetrate the cell membrane, which may contribute to inhibition of the middle stage of ZIKV infection. BR2GK blocked ZIKV E protein expression with an IC50 of 3.408 ± 0.738 μΜ. In summary, BR2GK was found to be a multi-functional candidate and a potential lead compound for further development of anti-ZIKV drugs.

A review of the antiviral activity of cationic antimicrobial peptides

“…Eight AVPs have been identified with the ability to inhibit Zika virus infection. The AVP brevinine-2GHk (isolated from from skin of southeast Asian frog) disrupts the envelope integrity by binding with the ZIKV E protein [80] . Hc-CATH, a cathelicidin from snake skin, targets the envelope and interferes with the downregulation of the AXL kinase receptor.…”

Human Claudin-Derived Peptides Block the Membrane Fusion Process of Zika Virus and Are Broad Flavivirus Inhibitors

“…Electron microscopic observations did not evidence particle aggregation. In other models, antiviral peptides are virucidal as they form pores in the viral lipid envelope, disrupting viral integrity ( 7 – 10 , 30 ). We found no such effect.…”

“…Their mechanisms of action are quite diverse. Some anti-ZIKV peptides disrupt the integrity of the viral particles, therefore preventing infection in vitro ( 7 ) and in vivo ( 8 – 10 ), while others have been shown to interact with viral proteins and interfere with their functions in vitro ( 11 ). In many cases, their mechanism remains unclear ( 12 – 14 ).…”

Novel Amphibian Bowman–Birk-Like Inhibitor with Antioxidant and Anticoagulant Effects Ameliorates Pancreatitis Symptoms in Mice

“…Ranacyclins with high sequence homology to Ranacin were obtained by BLAST and were aligned using the ClustalW method (). The docking complex between the structure of Ranacin constructed according to NMR analysis results and trypsin (PDB ID: 1SFI) was performed by the ZDOCK server and analyzed by PyMOL software as described previously …”