PDF(Pubmed)
Abstract：
Alphaviruses, belonging to the Togaviridae family, and bunyaviruses, belonging to the Paramyxoviridae family, are globally distributed and lack FDA-approved vaccines and therapeutics. The alphaviruses Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV) are known to cause severe encephalitis, whereas Sindbis virus (SINV) causes arthralgia potentially persisting for years after initial infection. The bunyavirus Rift Valley Fever virus (RVFV) can lead to blindness, liver failure, and hemorrhagic fever. Brilacidin, a small molecule that was designed de novo based on naturally occurring host defensins, was investigated for its antiviral activity against these viruses in human small airway epithelial cells (HSAECs) and African green monkey kidney cells (Veros). This testing was further expanded into a non-enveloped Echovirus, a Picornavirus, to further demonstrate brilacidin\'s effect on early steps of the viral infectious cycle that leads to inhibition of viral load. Brilacidin demonstrated antiviral activity against alphaviruses VEEV TC-83, VEEV TrD, SINV, EEEV, and bunyavirus RVFV. The inhibitory potential of brilacidin against the viruses tested in this study was dependent on the dosing strategy which necessitated compound addition pre- and post-infection, with addition only at the post-infection stage not eliciting a robust inhibitory response. The inhibitory activity of brilacidin was only modest in the context of the non-enveloped Picornavirus Echovirus, suggesting brilacidin may be less potent against non-enveloped viruses.
摘要：
α病毒,属于Togaviridae家族，和布尼亚病毒，属于副粘病毒科，全球分布，缺乏FDA批准的疫苗和疗法。已知α病毒委内瑞拉马脑炎病毒（VEEV）和东部马脑炎病毒（EEEV）会引起严重的脑炎，而辛德毕斯病毒（SINV）引起关节痛，可能在初次感染后持续数年。布尼亚病毒裂谷热病毒（RVFV）可导致失明，肝功能衰竭,和出血热.Brilacidin,一种基于天然宿主防御素从头设计的小分子，研究了其在人类小气道上皮细胞（HSAECs）和非洲绿猴肾细胞（Veros）中对这些病毒的抗病毒活性。这项测试进一步扩展到无包膜回声病毒，一种小核糖核酸病毒,进一步证明灯红肽对病毒感染周期早期步骤的影响，导致病毒载量的抑制。Brilacidin证明了对甲病毒VEEVTC-83，VEEVTrD的抗病毒活性，SINV,EEEV,和布尼亚病毒RVFV。在这项研究中测试的病毒的抑制性潜力是依赖于给药策略，这需要在感染前和感染后添加化合物。仅在感染后阶段添加，不会引起强烈的抑制反应。在无包膜小核糖核酸病毒Echovirus的情况下，灯乐碱的抑制活性仅为适度的，这表明灯盏细辛可能对无包膜病毒的效力较低。
