Structure-based Druggability Assessment of Anti-virulence Targets from Pseudomonas aeruginosa

Current Protein and Peptide Science - Tập 20 Số 12 - Trang 1189-1203 - 2019
Thamires Quadros Froes1, Regina L. Baldini2, Sándor Vajda3, Marcelo Santos Castilho1
1Programa de Pos-Graduacao em Biotecnologia da Universidade Estadual de Feira de Santana, Feira de Santana, BA, Brazil
2Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo. Sao Paulo, SP, Brazil
3College of Engineering, Boston University, Boston, MA, United States

Tóm tắt

Antimicrobial Resistance (AMR) represents a serious threat to health and the global economy. However, interest in antibacterial drug development has decreased substantially in recent decades. Meanwhile, anti-virulence drug development has emerged as an attractive alternative to fight AMR. Although several macromolecular targets have been explored for this goal, their druggability is a vital piece of information that has been overlooked. This review explores this subject by showing how structure- based freely available in silico tools, such as PockDrug and FTMap, might be useful for designing novel inhibitors of the pyocyanin biosynthesis pathway and improving the potency/selectivity of compounds that target the Pseudomonas aeruginosa quorum sensing mechanism. The information provided by hotspot analysis, along with binding site features, reveals novel druggable targets (PhzA and PhzS) that remain largely unexplored. However, it also highlights that in silico druggability prediction tools have several limitations that might be overcome in the near future. Meanwhile, anti-virulence drug targets should be assessed by complementary methods, such as the combined use of FTMap/PockDrug, once the consensus druggability classification reduces the risk of wasting resources on undruggable proteins.

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Current Protein and Peptide Science

Tập 20 Số 12

1189-1203

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