Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides

© The Author (2015). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.comSupplementary data are available at http://bioinformatics.oxfordjournals.org/lookup/suppl/doi:10.1093/bioinformatics/btv131/-/DC1Motivation: The need for more effective and safer pharmaceuticals is a persistent quest. Microbial adaptations create the need to permanently develop new antimicrobials, for instance. Similarly, intracellular delivery of drugs is still a challenge and translocation of membranes for drug delivery is an area of intense research. Peptides can be used both as antimicrobial drug leads and drug carrier systems for intracellular delivery. Multifunctional proteins are abundant in viruses but, surprisingly, have never been thoroughly screened for bioactive peptide sequences. Results: Using the AMPA and CellPPD online tools we have evaluated the propensity of viral proteins to comprise antimicrobial (AMP) or cell-penetrating peptides (CPP). Capsid proteins from both enveloped and non-enveloped viruses, and membrane and envelope proteins from enveloped viruses, in a total of 272 proteins from 133 viruses, were screened to detect the presence of potential AMP and CPP sequences. A pool of 2444 and 426 CPP and AMP sequences, respectively, were discovered. The capsids of flaviviruses are the best sources of these peptides reaching more than 80% of CPP sequence coverage per protein. Selected sequences were tested experimentally and validated the results. Overall, this study reveals that viruses form a natural multivalent biotechnological platform still underexplored in drug discovery and the heterogeneous abundance of CPP/AMP sequences among viral families opens new avenues in viral biology research.JMF and ASV acknowledge FCT-MEC for PhD fellowship SFRH/BD/70423/2010 and fellowship F/00803/2012 under the FCT Investigator Programme. Funding: Fundação para a Ciência e Tecnologia – Ministério da Educação e Ciência (FCT-MEC, Portugal) [HIVERA/0002/2013]