Host Defense Peptides: Exploiting an Innate Immune Component Against Infectious Diseases and Cancer

This review aims to elucidate the mechanisms employed by Host Defense Peptides (HDPs) in propagating their effector functions, associated bottlenecks complicating their therapeutic applications, and how these peptides can be optimized or modified as potential next-generation lead agents in targeted therapy in managing infectious diseases and cancer.

Emerging studies are affirming that due to dwindling therapeutic options, infectious diseases and cancers undoubtedly remain major threats to public health. This is mostly attributable to the toxicity and resistance of classical drugs in combating these health challenges, thus, novel bio-inspired treatment strategies are being sought. As the first line of defense in all organisms, the innate immune system produces many immune effector molecules including a group of biologically active endogenous peptides collectively known as Host Defense Peptides (HDPs), which can be further sub-classified into Antimicrobial Peptides (AMPs), or Anticancer Peptides (ACPs) based on their effector functions. These highly diverse, ubiquitous, and low-molecular-weight biomolecules are being identified and proposed as models for new drug/lead candidates. This is owing to their unique mechanism of action, sequence, and structural diversities which are integral to their downstream biological functions. Therefore, continuous efforts to elucidate the exploitability of these quintessential peptides in drug discovery research against these pathologies are worth exploring.

The ubiquity, significant diversities, and neoteric novel biological activities of HDPs as one of the effectors of the innate immune system establish them as a unique and valuable therapeutic strategy for combating infectious diseases and cancer. They are especially becoming prominent in overcoming the limitations posed by conventional therapeutic agents in managing these diseases, making them promising candidates for future drug development. Furthermore, their diverse functions and numerous molecular targets will play a crucial role in their discovery as new therapeutics.