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 phosphoprotein of 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 phytocompounds were 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. Molecular dynamic simulation of the best three protein- ligand complexes (alizarin, aloe-emodin and anthrarufin) was performed to study the interaction stability. 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. From MD simulation data, we found that all three complexes of 6VYO with alizarin, aloe-emodin and anthrarufin were stable up to 50 ns. These phytocompounds can be tested further for in vitro or in vivo and used as a potential drug to cure SARS-CoV-2 infection. Communicated by Ramaswamy H. Sarma
Highlights
During the end of year 2019, a venomous corona disease was emerged from the city of Wuhan, China [1]
The structure of N-terminal domain (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
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, aloeemodin, anthrarufin, alizarine, and dantron were -8.299, -8.508, -8.456, -8.441, and -8.322 Kcal mol-1 respectively, -7.714, -6.433, -6.354, -6.598, and -6.99 Kcal mol-1 respectively, and -8.299, 8.508, 8.538, 8.841, and 8.322 Kcal mol-1 respectively.All the active phytocompounds follows the drug likeness properties, non-carcinogenic, and non-toxic
Summary
During the end of year 2019, a venomous corona disease was emerged from the city of Wuhan, China [1]. The 3’- end of the RNA genome encodes for 13 ORFs for four structural proteins, such as the matrix (M), small envelope (E), spike (S) and nucleocapsid phosphoprotein (N), and facilitate entry of SARS-CoV-2entry to human cells through human angiotensin converting enzyme 2 (ACE2) receptor [2]. Both structural and nonstructural proteins ensure virus entry into the cells and its replication inside the host cell and serve as potential as drug targets. NTD of nucleocapsid (N) protein RNA binding domains could be one of the essential drug targets to prevent assembly of virus particles [15]
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