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

• Published in: Scientific reports Vol. 11; no. 1; pp. 8717 - 12
• Main Authors: Santos, Igor Andrade, Shimizu, Jacqueline Farinha, de Oliveira, Débora Moraes, Martins, Daniel Oliveira Silva, Cardoso-Sousa, Léia, Cintra, Adélia Cristina Oliveira, Aquino, Victor Hugo, Sampaio, Suely Vilela, Nicolau-Junior, Nilson, Sabino-Silva, Robinson, Merits, Andres, Harris, Mark, Jardim, Ana Carolina Gomes
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.04.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326; 631/326/596; 631/326/596/1282; 631/326/596/1296; Animals; Antiparasitic agents; Antiviral activity; Cell Line; Chikungunya virus; Chikungunya virus - drug effects; Chikungunya virus - physiology; Cricetinae; Crotalid Venoms - enzymology; Crotalus; Crotalus durissus terrificus; Fever; Glycoproteins; Glycoproteins - metabolism; Humanities and Social Sciences; Hydrophobicity; Inflammation; Infrared spectroscopy; Molecular Docking Simulation; multidisciplinary; Phospholipase A2; Phospholipases A2 - isolation & purification; Phospholipases A2 - metabolism; Phospholipases A2 - pharmacology; Protein Binding; Public health; Science; Science (multidisciplinary); Vector-borne diseases; Venom; Virions; Virus Internalization - drug effects; Virus Replication - drug effects; Viruses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-88039-4

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.