In silico investigation of phenolic derivatives from Silybum marianum against SARS-CoV-2 proteins as a pharmacological drug repurposing strategies to mitigate the pandemic.

Background: and Aim: The boutade of coronavirus disease-2019(COVID-19) has a striking impact on the worldwide healthcare system within a very short period of time. Availability of a large number of clinical data on SARS-CoV-2, conventional precautionary majors, and treatment strategies with the existing therapeutic antiviral drug molecules are also failing to control progression and disease transmission among the population. Hence, we implemented pharmacoinformatics approaches to facilitate the drug discovery process by repurposing naturally available therapeutic molecules as an effective intervention. Experimental Procedure: The major phenolic derivatives of Silybum marianum(Milk thistle) have been identified and investigated for ADME(Absorption, Distribution, Metabolism and Excretion)/tox properties. Co-crystallized structure of three major proteins(i.e. Main protease, RNA binding domain of nucleocapsid phosphoprotein and Spike receptor binding domain) from SARS-CoV-2 investigated with molecular docking(MD) interaction with the phenolic compounds from milk thistle. Furthermore, based on ADMET and MD interaction a 100ns MD simulation was performed with silibinin molecule. Outcomes: Being less toxic in ADME, a good MD interaction and stability of silibinin molecule across the MD simulation trajectories with targeted proteins explicate that silibinin molecule can be a promising drug candidate against the main protease and will be helpful to cease the enzymatic activity in viral replication and transcription.