Phospholipase A(2) Isolated from the Venom of Crotalus durissus terrificus Inactivates Dengue virus and Other Enveloped Viruses by Disrupting the Viral Envelope

Autor(es)

Muller, Vanessa Danielle ^[1] ; Soares, Ricardo Oliveira ^[2] ; dos Santos-Junior, Nilton Nascimento ^[1] ; Trabuco, Amanda Cristina ^[1] ; Cintra, Adelia Cristina ^[3] ; Figueiredo, Luiz Tadeu ^[4] ; Caliri, Antonio ^[2] ; Sampaio, Suely Vilela ^[3] ; Aquino, Victor Hugo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Virol Lab, Dept Anal Clin Toxicol & Bromatol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Lab Toxinol, Dept Anal Clin Toxicol & Bromatol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, Ctr Pesquisa Virol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 9, n. 11 NOV 10 2014.
• Citações Web of Science: 20

Resumo

The Flaviviridae family includes several virus pathogens associated with human diseases worldwide. Within this family, Dengue virus is the most serious threat to public health, especially in tropical and sub-tropical regions of the world. Currently, there are no vaccines or specific antiviral drugs against Dengue virus or against most of the viruses of this family. Therefore, the development of vaccines and the discovery of therapeutic compounds against the medically most important flaviviruses remain a global public health priority. We previously showed that phospholipase A(2) isolated from the venom of Crotalus durissus terrificus was able to inhibit Dengue virus and Yellow fever virus infection in Vero cells. Here, we present evidence that phospholipase A(2) has a direct effect on Dengue virus particles, inducing a partial exposure of genomic RNA, which strongly suggests inhibition via the cleavage of glycerophospholipids at the virus lipid bilayer envelope. This cleavage might induce a disruption of the lipid bilayer that causes a destabilization of the E proteins on the virus surface, resulting in inactivation. We show by computational analysis that phospholipase A(2) might gain access to the Dengue virus lipid bilayer through the pores found on each of the twenty 3-fold vertices of the E protein shell on the virus surface. In addition, phospholipase A(2) is able to inactivate other enveloped viruses, highlighting its potential as a natural product lead for developing broad-spectrum antiviral drugs. (AU)

• Processo FAPESP: 08/50617-6 - Estudos sobre vírus emergentes incluindo arbovirus, robovirus, vírus respiratórios e de transmissão congênita, no Centro de Pesquisa em Virologia da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo
• Beneficiário: Luiz Tadeu Moraes Figueiredo
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 05/54855-0 - Toxinas animais: estrutura, função e aplicações biotecnológicas
• Beneficiário: Suely Vilela
• Modalidade de apoio: Auxílio à Pesquisa - Temático