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.

Highlights

  • Zika virus (ZIKV) refers to a member of the family Flaviviridae

  • Four methods were adopted to treat the cells, and the possible anti-ZIKV effects of BR2GK were evaluated by the plaque assay

  • BR2GK, at a concentration of 20 μM, significantly reduced the number of plaques induced by ZIKV in the virus-treatment, cotreatment, and post-treatment methods (Figure 1C)

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Summary

Introduction

Zika virus (ZIKV) refers to a member of the family Flaviviridae. It was initially isolated in 1947 from a rhesus monkey in the Zika forest of Uganda [1]. Up till December 2019, ZIKV had been detected in 87 nations, territories, and subnational areas [3]. The most common clinical presentations of ZIKV infection consist of fever, rash, headache, joint pain, and conjunctivitis [5]. The genome of ZIKV consists of a (+)-strand ssRNA molecule of nearly 10.7 kb, encoding a polyprotein precursor that is cleaved and processed by the viral protease NS3 into seven non-structural (NS) and three structural proteins (i.e., capsid (C), pre-membrane (prM), and envelope (E)). The NS proteins are involved in viral polyprotein processing, genome replication, and operation of host responses for viral benefit, while the structural proteins form the virus particle [7]

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