Abstract

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 A2CB (PLA2CB), 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 PLA2CB on the CHIKV replicative cycle in BHK-21 cells using CHIKV-nanoluc, a marker virus carrying nanoluciferase reporter. The results demonstrated that PLA2CB possess a strong anti-CHIKV activity with a selectivity index of 128. We identified that PLA2CB treatment protected cells against CHIKV infection, strongly impairing virus entry by reducing adsorption and post-attachment stages. Moreover, PLA2CB presented a modest yet significant activity towards post-entry stages of CHIKV replicative cycle. Molecular docking calculations indicated that PLA2CB may interact with CHIKV glycoproteins, mainly with E1 through hydrophobic interactions. In addition, infrared spectroscopy measurements indicated interactions of PLA2CB and CHIKV glycoproteins, corroborating with data from in silico analyses. Collectively, this data demonstrated the multiple antiviral effects of PLA2CB on the CHIKV replicative cycle, and suggest that PLA2CB interacts with CHIKV glycoproteins and that this interaction blocks binding of CHIKV virions to the host cells.

Details

Title
Chikungunya virus entry is strongly inhibited by phospholipase A2 isolated from the venom of Crotalus durissus terrificus
Author
Santos, Igor Andrade 1 ; Shimizu, Jacqueline Farinha 2 ; de Oliveira Débora Moraes 1 ; Oliveira Silva, Martins Daniel 2 ; Cardoso-Sousa Léia 1 ; Cintra Adélia Cristina Oliveira 3 ; Aquino, Victor Hugo 3 ; Sampaio Suely Vilela 3 ; Nicolau-Junior Nilson 4 ; Sabino-Silva, Robinson 1 ; Merits Andres 5 ; Harris, Mark 6 ; Jardim Ana Carolina Gomes 2 

 Federal University of Uberlândia (UFU), Institute of Biomedical Science (ICBIM), Uberlândia, Brazil (GRID:grid.411284.a) (ISNI:0000 0004 4647 6936) 
 Federal University of Uberlândia (UFU), Institute of Biomedical Science (ICBIM), Uberlândia, Brazil (GRID:grid.411284.a) (ISNI:0000 0004 4647 6936); São Paulo State University (Unesp), Institute of Biosciences, Humanities and Exact Sciences (Ibilce), São José do Rio Preto, Brazil (GRID:grid.410543.7) (ISNI:0000 0001 2188 478X) 
 University of São Paulo (USP), Department of Clinical, Toxicological and Bromatological Analyses, School of Pharmaceutical Sciences of Ribeirao Preto, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722) 
 Federal University of Uberlândia (UFU), Institute of Biotechnology, Uberlândia, Brazil (GRID:grid.411284.a) (ISNI:0000 0004 4647 6936) 
 University of Tartu, Institute of Technology, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661) 
 University of Leeds, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2516597514
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.