Exploring Aspartate Semialdehyde Dehydrogenase as a Prospective Drug Target for Fungal Pathogens: An Extensive Molecular Modeling Studies
Year: 2024
Type: article
Abstract: Trichophyton rubrum (T. rubrum) and Blastomyces dermatitidis (B. dermatitidis) are two fungal species that pose significant threats to human health. T. rubrum is a dermatophyte fungus that causes athlete’s foot, fungal nail infections, and jock itch, and the ringworm B. dermatitidis is a dimorphic fungus that causes blastomycosis. Aspartate semialdehyde dehydrogenase (ASADH) is an enzyme that catalyzes the reductive dephosphorylation of β-aspartyl phosphate to L-aspartate-β-semialdehyde in the aspartate biosynthetic pathway of plants and microorganisms. The inhibition of ASADH has resulted in a substantial reduction in the populations of several pathogenic microbial organisms. An extensive literature review revealed that ASADH could be considered a promising drug target for identifying and developing compounds with potent antifungal activity. Therefore, in the present study, a comprehensive in silico screening of compound libraries was initially carried out to identify possible ASADH inhibitors. The chosen drug targets (ASADH from T. rubrum and B. dermatitidis) were subsequently subjected to molecular docking with those chemical libraries via PyRx. The results revealed that in each library, a subset of potential small molecules exhibited higher binding affinities for T. rubrum and B. dermatitidis’s ASADH. In addition, analysis of their physicochemical and ADMET properties confirmed that several of the higher-ranked compounds exhibited drug-likeness properties. Taken together, our findings show that the compounds identified in the present study open new avenues for drug development, and further in vitro and in vivo validation studies are needed to assess their efficacy and safety profiles for the development of novel antifungal treatments.
Authors: Lakshminarayanan Karthik -, Swathi Nataraj -, Shristi Saini -, Oruganti Amsu Madhu Deepika -
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: hybrid
OpenAlex ID: W4403862972