Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides.
BACKGROUND
The need for more effective and safer pharmaceuticals is a persistent quest. Microbial adaptations create the need to permanently develop new antimicrobials (AMPs), 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 AMP 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 AMP or cell-penetrating peptides (CPPs). 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.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.
João Miguel
JM
Freire
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.
Susana
S
Almeida Dias
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.
Luís
L
Flores
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.
Ana Salomé
AS
Veiga
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.
Miguel A R B
MA
Castanho
D000890:Anti-Infective Agents / Q000737:chemistry*; D036022:Capsid Proteins / Q000737:chemistry; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry; D020539:Sequence Analysis, Protein; D014764:Viral Proteins / Q000737:chemistry*
D000890:Anti-Infective Agents; D036022:Capsid Proteins; D057846:Cell-Penetrating Peptides; D008565:Membrane Proteins; D014764:Viral Proteins