Computational Elucidation of Human β-Defensin-2 as a Dual Inhibitor of MMP-9 and PKC-βII for Diabetic Wound Management.

Diabetic wounds (DWs) are the most devastating complication, resulting in significant mortality and morbidity in diabetic patients. Although the pathophysiology of DWs is multifaceted, evidence has revealed that prolonged inflammation with infections, extracellular matrix (ECM) degradation, and unnecessary NETosis impair DW healing. This theoretical problem highlights the necessity of developing a novel strategy focused on targeting the "specific" molecular modalities of DWs. The primary culprits, matrix metalloproteinase (MMP)-9 and protein kinase C (PKC)-βII, are responsible for impaired angiogenesis, NETosis, and ECM degradation. Thus, interest in identifying selective inhibitors for the effective management of DW has increased. The current study exemplified human β-defensin-2 (HBD-2), a biological macromolecule that functions as a dual inhibitor of MMP-9 and PKC-βII, via protein-protein docking and molecular dynamics simulation studies. Overall, the data analysis revealed that HBD-2 possesses strong binding affinity and stability against MMP-9 and PKC-βII, suggesting that HBD-2 may be an ideal therapeutic for the accelerated healing of DW. Our findings suggest HBD-2's potential as an innovative therapeutic for accelerated DW healing, offering valuable insights into its molecular mechanisms. However, in vitro and in vivo studies are required to bridge the gap between computational modeling and clinical application.