Evaluating Terrestrol A as an Inhibitor Against SARS‐CoV‐2and Invasive Fungal Pathogens: A Comprehensive Computational Analysis

Abstract

AbstractThe highly contagious SARS‐CoV‐2 virus, which initiated the COVID‐19 pandemic, has resulted in a significant loss of life worldwide. While vaccines and therapeutics have helped mitigate the impact of SARS‐CoV‐2, worries still persist regarding the emergence of Variants of Concern (VOCs). Additionally, the immunosuppressive effects of SARS‐CoV‐2 and steroid treatments increase susceptibility to complex fungal co–infections (e. g., aspergillosis and candidiasis), complicating treatment and escalating mortality rates. These circumstances highlight the urgent need for novel therapeutics. Thus, this study explores gentisyl alcohol and its derivatives as inhibitors of SARS‐CoV‐2 and fungal pathogens (Aspergillus fumigatus and Candida auris) via in‐silico methodologies. Initial multi–targeted docking simulations revealed that Terrestrol A(10) exhibited highly promising results, displaying the most favourable MolDock‐scores against all targets of interest, particularly against PDB ID 4K90 and 7CR5. The subsequent assessment of Terrestrol A(10) for their druglikeness, ADME, toxicity profiling, bioactivity, and PASS prediction also yielded highly favourable results. Structural dynamics analysis revealed stable yet slightly unfolding complexes, affirming their integrity. DFT studies also demonstrated favourable reactivity of Terrestrol A(10). This investigation identifies Terrestrol A(10) as a highly promising inhibitor against SARS‐CoV‐2 and fungal pathogens, laying the groundwork for in vitro and in vivo validation of its efficacy and clinical utility.