文章基本信息

标题：Chikungunya virus entry is strongly inhibited by phospholipase A2 isolated from the venom of Crotalus durissus terrificus
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作者：Igor Andrade Santos ; Jacqueline Farinha Shimizu ; Débora Moraes de Oliveira 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2021
卷号：11
DOI：10.1038/s41598-021-88039-4
语种：English
出版社：Springer Nature
摘要：Chikungunya virus (CHIKV) is the etiologic agent of Chikungunya fever, a globally spreading mosquito-borne disease. There is no approved antiviral or vaccine against CHIKV, highlighting an urgent need for novel therapies. In this context, snake venom proteins have demonstrated antiviral activity against several viruses, including arboviruses which are relevant to public health. In particular, the phospholipase A2 CB (PLA2 CB), a protein isolated from the venom of Crotalus durissus terrificus was previously shown to possess anti-inflammatory, antiparasitic, antibacterial and antiviral activities. In this study, we investigated the multiple effects of PLA2 CB on the CHIKV replicative cycle in BHK-21 cells using CHIKV- nanoluc, a marker virus carrying nanoluciferase reporter. The results demonstrated that PLA2 CB possess a strong anti-CHIKV activity with a selectivity index of 128. We identified that PLA2 CB treatment protected cells against CHIKV infection, strongly impairing virus entry by reducing adsorption and post-attachment stages. Moreover, PLA2 CB presented a modest yet significant activity towards post-entry stages of CHIKV replicative cycle. Molecular docking calculations indicated that PLA2 CB may interact with CHIKV glycoproteins, mainly with E1 through hydrophobic interactions. In addition, infrared spectroscopy measurements indicated interactions of PLA2 CB and CHIKV glycoproteins, corroborating with data from in silico analyses. Collectively, this data demonstrated the multiple antiviral effects of PLA2 CB on the CHIKV replicative cycle, and suggest that PLA2 CB interacts with CHIKV glycoproteins and that this interaction blocks binding of CHIKV virions to the host cells.