In silico screening of hundred phytocompounds of ten medicinal plants as potential inhibitors of nucleocapsid phosphoprotein of COVID-19: An approach to prevent virus assembly

Abstract

Currently, there is no specific treatment to cure COVID-19. Many medicinal plants have antiviral, antioxidant, antibacterial, antifungal, anticancer, wound healing etc. Therefore, the aim of the current study was to screen for potent inhibitors of N-terminal domain (NTD) of nucleocapsid phosphoproteinof SARS-CoV-2. The structure of NTD of RNA binding domain of nucleocapsid phosphoprotein of SARS coronavirus 2 was retrieved from the Protein Data Bank (PDB 6VYO)and the structures of 100 different phytocompoundswere retrieved from Pubchem. The receptor protein and ligands were prepared using Schrodinger’s Protein Preparation Wizard. Molecular docking was done by using the Schrodinger’s maestro 12.0 software. Drug likeness and toxicity of active phytocompounds was predicted by using Swiss adme, admetSAR and protox II online servers. We have identified three potential active sites (named as A, B, C) on receptor protein for efficient binding of the phytocompounds. We found that, among 100 phytocompounds, emodin, aloe-emodin, anthrarufin, alizarine, and dantron of Rheum emodi showed good binding affinity at all the three active sites of RNA binding domain of nucleocapsid phosphoprotein of COVID-19.The binding energies of emodin, aloe-emodin, anthrarufin, alizarine, and dantron were -8.299 , -8.508, -8.456, -8.441, and -8.322 Kcal mol-1 respectively (site A), -7.714, -6.433, -6.354, -6.598, and -6.99 Kcal mol-1 respectively (site B), and -8.299, 8.508, 8.538, 8.841, and 8.322 Kcal mol-1 respectively (site C).All the active phytocompounds follows the drug likeness properties, non-carcinogenic, and non-toxic. Theses phytocompounds (alone or in combination) could be developed into effective therapy against COVID-19.

Assembly and Entry of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2): Evaluation Using Virus-Like Particles

“…The VLPs can, however, provide assay platforms for particle assembly and its inhibition. SARS-CoV2 assembly is a target for pharmacologic inhibition, and in silico approaches have identified several phytocompounds [ 53 , 54 ] and anti-viral and anti-microbial drugs [ 55 , 56 ], which may prove effective against SARS-CoV2. These computational methods help in designing of new drug candidates more rapidly, however, their actual validation in natural viral infection takes time and resources due to limitations of required biosafety facilities to handle highly pathogenic viruses.…”

An Overview on Antiviral Potential of Traditional Medicines

“…These compounds prevent the assembly of virus particles and stop the infection. They are suggested as potential drugs for COVID-19 treatment [24]. From secondary metabolites, curcumin as the main constituent of Curcuma longa L. (turmeric), is the reputed compound displaying remarkable biological activities for human health.…”

Tartary Buckwheat in Human Nutrition

“…Emodin ( Figure 4 ) has been reported for the bran and leaves of Tartary buckwheat [ 91 ]. It appears to be a precursor in the synthesis of hypericin, and of Tartary buckwheat fagopyrin [ 92 ]. Of importance here, emodin isolated from Tartary buckwheat grain has been shown to dock into all three active sites of the RNA-binding domain of the nucleocapsid phosphoprotein of SARS-CoV-2 [ 91 , 92 , 93 , 94 ].…”