3CLpro and PLpro affinity, a docking study to fight COVID19 based on 900 compounds from PubChem and literature. Are there new drugs to be found?
The emergence of the novel coronavirus SARS-CoV-2 and the resulting COVID-19 disease in late 2019 has led to a global pandemic, bringing much of the world to a standstill. The proteases 3CLpro and PLpro, which are crucial for the proteolysis of new virions, represent important targets for COVID-19 treatment. In this study, we present an in silico docking analysis of over 860 COVID-19-related compounds sourced from the PubChem database. Molecular dynamics simulations were conducted to assess the conformational stability of the compound-ligand complexes with the highest docking scores. We utilized the MM-PBSA method to calculate binding free energies.
Our findings include a comparison with approximately 50 previously identified potential inhibitors of SARS-CoV-2 proteases, revealing several new compounds with strong binding affinities. Notably, anti-inflammatory drugs such as Montelukast, Ebastine, and Solumedrol, along with the anti-migraine medication Vazegepant and the anti-MRSA pro-drug TAK-599, demonstrated significant affinities for 3CLpro. Given their known side effects, these compounds are promising candidates for immediate clinical trials.
This study provides a comprehensive summary of docking scores for COVID-19-related compounds from the PubChem database and highlights the value of computational screening methods in identifying potential drug candidates. Several untested compounds exhibited affinities comparable to those of reported inhibitors, suggesting they merit further investigation. Additionally, the submitted work includes ADME data, ZINC and PubChem IDs, and docking scores for all compounds studied, facilitating further comparisons.