Exoproteome and secretome derived broad spectrum novel drug and vaccine candidates in Vibrio cholerae targeted by Piper betel derived compounds

• Published in: PloS one Vol. 8; no. 1; p. e52773
• Main Authors: Barh, Debmalya, Barve, Neha, Gupta, Krishnakant, Chandra, Sudha, Jain, Neha, Tiwari, Sandeep, Leon-Sicairos, Nidia, Canizalez-Roman, Adrian, dos Santos, Anderson Rodrigues, Hassan, Syed Shah, Almeida, Síntia, Ramos, Rommel Thiago Jucá, de Abreu, Vinicius Augusto Carvalho, Carneiro, Adriana Ribeiro, Soares, Siomar de Castro, Castro, Thiago Luiz de Paula, Miyoshi, Anderson, Silva, Artur, Kumar, Anil, Misra, Amarendra Narayan, Blum, Kenneth, Braverman, Eric R, Azevedo, Vasco
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30-01-2013; Public Library of Science (PLoS)
• Subjects: Biology; Cholera; Cholera - drug therapy; Cholera - immunology; Cholera - microbiology; Cholera toxin; Comparative analysis; Computer Science; Development and progression; Drug Discovery; Drug resistance; Epitopes, T-Lymphocyte - immunology; Generic drugs; Health aspects; Humans; Ligands; Medicine; Piper betle - chemistry; Proteome; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology; T cells; Vaccines; Vaccines, Subunit - chemistry; Vaccines, Subunit - pharmacology; Vibrio cholerae - drug effects; Vibrio cholerae - immunology; Vibrio cholerae - pathogenicity
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0052773

Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC) for most of the pathogenic Vibrio strains. Two targets (uppP and yajC) are novel to Vibrio, and two targets (uppP and ompU) can be used to develop both drugs and vaccines (dual targets) against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species.