Infectious
diseases are a major cause of morbidity and mortality
worldwide, exacerbated by increasing antibiotic resistance in many
bacterial species. The development of drugs with new modes of action
is essential. A leading strategy is antivirulence, with the aim to
target bacterial proteins that are important in disease causation
and progression but do not affect growth, resulting in reduced selective
pressure for resistance. Immunophilins, a superfamily of peptidyl-prolyl cis–trans isomerase (PPIase) enzymes
have been shown to be important for virulence in a broad-spectrum
of pathogenic bacteria. This Perspective will provide an overview
of the recent advances made in understanding the role of each immunophilin
family, cyclophilins, FK506 binding proteins (FKBPs), and parvulins
in bacteria. Inhibitor design and medicinal chemistry strategies for
development of novel drugs against bacterial FKBPs will be discussed.
Furthermore, drugs against human cyclophilins and parvulins will be
reviewed in their current indication as antiviral and anticancer therapies.
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