Real-world application of molecular docking in drug discovery

Computational drug designing comprising mainly Molecular Docking has surged in popularity due to its efficiency and precision in identifying potential therapeutic candidates, often collectively referred to as virtual screening. This method enables researchers to screen large compound libraries virtually, significantly speeding up the initial stages of drug development. The significance of molecular docking is particularly evident in the fight against rapidly evolving pathogens like SARS-CoV-2. Lately, the emergence of new COVID-19 variants, such as the highly transmissible XBB.1.5, is incessantly posing challenges. Conventional drug development approaches aimed on a single strain, outgazing the importance of virus' evolution which is well-facilitated by molecular docking that provides better assessment of therapeutic efficacy against multiple variants of this virus. In the present study, molecular docking was executed to screen potential phytochemicals against the spike protein XBB.1.5 variant, known for its critical mutations that enhance infectivity. As part of the entire screening protocol, other tools like Schrödinger's suite, SwissADME, and ProTox-II were utilized to identify the top leads. These computational facilitators assisted in estimation of binding affinity, pharmacokinetics and toxicity profiles. Estimation of these factors led to identification of promising lead compounds that depicted strong binding interactions against the mutated spike protein, suggesting their potential as broad-spectrum antiviral agents. The present study emphasizes the importance of computational tools and techniques like molecular docking in addressing the variants generated against continuous evolution of SARS-COV2. The methodologies adapted can be deployed against other disease towards development of targeted therapeutics, ensuring a proactive approach to global health threats.