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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<jats:sub>CB<\/jats:sub> (PLA2<jats:sub>CB<\/jats:sub>), a protein isolated from the venom of <jats:italic>Crotalus durissus terrificus<\/jats:italic> was previously shown to possess anti-inflammatory, antiparasitic, antibacterial and antiviral activities. In this study, we investigated the multiple effects of PLA2<jats:sub>CB<\/jats:sub> on the CHIKV replicative cycle in BHK-21 cells using CHIKV-<jats:italic>nanoluc<\/jats:italic>, a marker virus carrying <jats:italic>nanoluciferase<\/jats:italic> reporter. The results demonstrated that PLA2<jats:sub>CB<\/jats:sub> possess a strong anti-CHIKV activity with a selectivity index of 128. We identified that PLA2<jats:sub>CB<\/jats:sub> treatment protected cells against CHIKV infection, strongly impairing virus entry by reducing adsorption and post-attachment stages. Moreover, PLA2<jats:sub>CB<\/jats:sub> presented a modest yet significant activity towards post-entry stages of CHIKV replicative cycle. Molecular docking calculations indicated that PLA2<jats:sub>CB<\/jats:sub> may interact with CHIKV glycoproteins, mainly with E1 through hydrophobic interactions. In addition, infrared spectroscopy measurements indicated interactions of PLA2<jats:sub>CB<\/jats:sub> and CHIKV glycoproteins, corroborating with data from in silico analyses. Collectively, this data demonstrated the multiple antiviral effects of PLA2<jats:sub>CB<\/jats:sub> on the CHIKV replicative cycle, and suggest that PLA2<jats:sub>CB<\/jats:sub> interacts with CHIKV glycoproteins and that this interaction blocks binding of CHIKV virions to the host cells.<\/jats:p>","DOI":"10.1038\/s41598-021-88039-4","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T10:10:11Z","timestamp":1619086211000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Chikungunya virus entry is strongly inhibited by phospholipase A2 isolated from the venom of Crotalus durissus terrificus"],"prefix":"10.1038","volume":"11","author":[{"given":"Igor Andrade","family":"Santos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline Farinha","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora Moraes","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Oliveira Silva","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9ia","family":"Cardoso-Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad\u00e9lia Cristina Oliveira","family":"Cintra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Hugo","family":"Aquino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suely Vilela","family":"Sampaio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilson","family":"Nicolau-Junior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robinson","family":"Sabino-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Merits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina Gomes","family":"Jardim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"88039_CR1","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1099\/jgv.0.001072","volume":"99","author":"R Chen","year":"2018","unstructured":"Chen, R. et al. 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