Chikungunya virus entry is strongly inhibited by phospholipase A2 isolated from the venom of Crotalus durissus terrificus

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 act...

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Autores principales:	Igor Andrade Santos, Jacqueline Farinha Shimizu, Débora Moraes de Oliveira, Daniel Oliveira Silva Martins, Léia Cardoso-Sousa, Adélia Cristina Oliveira Cintra, Victor Hugo Aquino, Suely Vilela Sampaio, Nilson Nicolau-Junior, Robinson Sabino-Silva, Andres Merits, Mark Harris, Ana Carolina Gomes Jardim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/95497c7a0e3b4bd78a66109113693206
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spelling	oai:doaj.org-article:95497c7a0e3b4bd78a661091136932062021-12-02T16:45:06ZChikungunya virus entry is strongly inhibited by phospholipase A2 isolated from the venom of Crotalus durissus terrificus10.1038/s41598-021-88039-42045-2322https://doaj.org/article/95497c7a0e3b4bd78a661091136932062021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88039-4https://doaj.org/toc/2045-2322Abstract 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.Igor Andrade SantosJacqueline Farinha ShimizuDébora Moraes de OliveiraDaniel Oliveira Silva MartinsLéia Cardoso-SousaAdélia Cristina Oliveira CintraVictor Hugo AquinoSuely Vilela SampaioNilson Nicolau-JuniorRobinson Sabino-SilvaAndres MeritsMark HarrisAna Carolina Gomes JardimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Igor Andrade Santos Jacqueline Farinha Shimizu Débora Moraes de Oliveira Daniel Oliveira Silva Martins Léia Cardoso-Sousa Adélia Cristina Oliveira Cintra Victor Hugo Aquino Suely Vilela Sampaio Nilson Nicolau-Junior Robinson Sabino-Silva Andres Merits Mark Harris Ana Carolina Gomes Jardim Chikungunya virus entry is strongly inhibited by phospholipase A2 isolated from the venom of Crotalus durissus terrificus
description	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.
format	article
author	Igor Andrade Santos Jacqueline Farinha Shimizu Débora Moraes de Oliveira Daniel Oliveira Silva Martins Léia Cardoso-Sousa Adélia Cristina Oliveira Cintra Victor Hugo Aquino Suely Vilela Sampaio Nilson Nicolau-Junior Robinson Sabino-Silva Andres Merits Mark Harris Ana Carolina Gomes Jardim
author_facet	Igor Andrade Santos Jacqueline Farinha Shimizu Débora Moraes de Oliveira Daniel Oliveira Silva Martins Léia Cardoso-Sousa Adélia Cristina Oliveira Cintra Victor Hugo Aquino Suely Vilela Sampaio Nilson Nicolau-Junior Robinson Sabino-Silva Andres Merits Mark Harris Ana Carolina Gomes Jardim
author_sort	Igor Andrade Santos
title	Chikungunya virus entry is strongly inhibited by phospholipase A2 isolated from the venom of Crotalus durissus terrificus
title_short	Chikungunya virus entry is strongly inhibited by phospholipase A2 isolated from the venom of Crotalus durissus terrificus
title_full	Chikungunya virus entry is strongly inhibited by phospholipase A2 isolated from the venom of Crotalus durissus terrificus
title_fullStr	Chikungunya virus entry is strongly inhibited by phospholipase A2 isolated from the venom of Crotalus durissus terrificus
title_full_unstemmed	Chikungunya virus entry is strongly inhibited by phospholipase A2 isolated from the venom of Crotalus durissus terrificus
title_sort	chikungunya virus entry is strongly inhibited by phospholipase a2 isolated from the venom of crotalus durissus terrificus
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/95497c7a0e3b4bd78a66109113693206
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Chikungunya virus entry is strongly inhibited by phospholipase A2 isolated from the venom of Crotalus durissus terrificus

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