Phospholipase A2 isolated from the venom of Crotalus durissus terrificus inactivates Dengue virus and other enveloped viruses by disrupting the viral envelope
| Autor: | A. Caliri, Victor Hugo Aquino, Amanda Cristina Trabuco, Nilton Nascimento Santos-Junior, Luiz Tadeu Moraes Figueiredo, Ricardo O. S. Soares, Adélia Cristina Oliveira Cintra, Suely Vilela Sampaio, Vanessa Danielle Menjon Muller |
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| Rok vydání: | 2014 |
| Předmět: |
Viral Diseases
Infectious Disease Control viruses Lipid Bilayers lcsh:Medicine SERPENTES Dengue virus Biology Phospholipase medicine.disease_cause Antiviral Agents Microbiology Virus Dengue Fever Flaviviridae Viral envelope Microbial Control Chlorocebus aethiops Crotalid Venoms medicine Medicine and Health Sciences Animals Antibody-dependent enhancement lcsh:Science Vero Cells Multidisciplinary Antimicrobials lcsh:R Crotalus Virion Biology and Life Sciences Dengue Virus biology.organism_classification Antivirals Yellow Fever Virus Infection Virology Phospholipases A2 Infectious Diseases Emerging Infectious Diseases Arboviral Infections Vero cell Virus Inactivation lcsh:Q Research Article |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP PLoS ONE PLoS ONE, Vol 9, Iss 11, p e112351 (2014) |
| Popis: | 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 A2 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 A2 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 A2 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 A2 is able to inactivate other enveloped viruses, highlighting its potential as a natural product lead for developing broad-spectrum antiviral drugs. |
| Databáze: | OpenAIRE |
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