, the disease caused by SARS-CoV-2, has been declared as a global pandemic. Traditional medicinal plants have long history to treat viral infections. Our in silico approach suggested that unique phytocompounds such as emodin, thymol and carvacrol, and artemisinin could physically bind SARS-CoV-2 spike glycoproteins (6VXX and 6VYB), SARS-CoV-2 B.1.351 South Africa variant of Spike glycoprotein (7NXA), and even with ACE2 and prevent the SARS-CoV-2 binding to the host ACE2, TMPRSS2 and neutrapilin-1 receptors. Since Chloroquine has been looked as potential therapy against COVID-19, we also compared the binding of chloroquine and artemisinin for its interaction with spike proteins (6VXX, 6VYB) and its variant 7NXA, respectively. Molecular docking study of phytocompounds and SARS-CoV-2 spike protein was performed by using AutoDock/Vina software. Molecular dynamics (MD) simulation was performed for 50ns. Among all the phytocompounds, molecular docking studies revealed lowest binding energy of artemisinin with 6VXX and 6VYB, with E total −10.5 KJ mol −1 and −10.3 KJ mol −1 respectively. Emodin showed the best binding affinity with 6VYB with E total −8.8 KJ mol −1 and SARS-CoV-2 B.1.351 variant (7NXA) with binding energy of −6.4KJ mol −1 . Emodin showed best interactions with TMPRSS 2 and ACE2 with E total of −7.1 and −7.3 KJ mol −1 respectively, whereas artemisinin interacts with TMPRSS 2 and ACE2 with E total of −6.9 and −7.4 KJ mol −1 respectively. All the phytocompounds were non-toxic and non-carcinogenic. MD simulation showed that artemisinin has more stable interaction with 6VYB as compared to 6VXX, and hence proposed as potential phytochemical to prevent SARS-CoV-2 interaction with ACE-2 receptor.
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
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.
COVID-19 has been declared as global epidemic and currently there is no drug/vaccine available to treat COVID-19. All over the world, several studies are being conducted to discover the antiviral drugs against COVI-19. Traditional medicinal plants have long history to treat viral infections. We adopted in silico approach to find out if unique phytocompounds such as emodin (Rheum emodi), thymol and carvacrol (Thymus serpyllum) and artemisnin (Artemisia annua) could physically bind COVID-19 target proteins such as SARS-CoV-2 spike glycoprotein (PDB ID: 6VXX), SARS-CoV-2 spike ectodomain structure (PDB ID: 6VYB), and SARS coronavirus spike receptor-binding domain (PDB ID: 2AJF) and in turn preventCOVID-19 binding to the host receptor ACE2. Since Chloroquine (a standard antimalarial drug) has been looked as potential therapy against COVID-19, we also compared the binding of chloroquine and plant origin artemisnin antimalarial drug for its interaction with 6VXX, 6VY and 2AJF. Molecular docking studies using AutoDock/Vina software revealed that among all the phytocompounds artemisinin showed best binding affinity with 6VXX, 6VYB and 2AJF with Etotal -10.5 KJ mol-1, -10.3 KJ mol-1, and -9.1 KJ mol-1 respectively. Whereas emodin, carvacrol and thymol binds with 6VXX, 6VYB and 2AJF with Etotal -6.4, -6.8, -6.9 KJ mol-1, -8.8, -6.8, -7.4 KJ mol-1, and -6.9, -7.4, -7.2 respectively. Similarly, with Autodock/Vina chloroquine showed less binding affinity with 6VXX (-5.6 KJ mol-1), 6VYB (-5.9 KJ mol-1) and 2AJF (-6.4 KJ mol-1) as compared to all phytocompounds. Toxicity prediction showed non-toxicity and non-carcinogen by admetSAR and PROTOX‑II software.
Rheum emodi Wall. (Himalayan rhubarb) has been used to cure many human diseases. Literature survey demonstrated that it has many pharmacological activities such as antioxidant, antimicrobial, antiviral, anticancer and wound healing. The present study was aimed to understand if major phytocompounds of Rheum emodi could bind proteins responsible for antibiotic resistance in bacterial and fungal pathogens and enhance the potency of antibiotics.The major phytocompounds of R. emodi (emodin, rhein-13c6 and chrysophenodimethy ether) were retrieved from Pubchem and target proteins were retrieved from RCSB protein data bank.The docking study was performed with Hex 8.0.0 software and molinspiration, swiss ADME servers were used for determination of Lipinski rule of 5, drug-likeness prediction respectively, whereas, admetSAR and Protox-II tools were used for toxicity prediction. Among all the selected phytocompounds, emodin showed the best binding energy of -235.82 Kcal mol -1 and -245 Kcal mol -1 with cytochrome P450 14 alpha-sterol demethylase (PDB ID: 1EA1) and N-myristoyl transferase (PDB ID: 1IYL) receptors, respectively, which is more than that of fluconazole (-224.12 kcalmol -1 and -161.14 kcal mol -1 ). Similarly, with Penicillin binding protein 3 (PDB ID: 3VSL) receptor, emodin and Chrysophanol dimethyl ether showed highest binding energy of -216.68 Kcal mol -1 and -215.58 kcal mol -1 which is comparable to erythromycin (-263.63 kcal mol -1 ), chloramphanicol (-217.34 kcal mol -1 ) and tetracycline (-263.63 kcal mol -1 ). All the selected phytocompounds also fulfill Lipinski rule, non-carcinogenic and non-cytotoxic in nature. These compounds also showed high LD 50 value showing non-toxicity of these phytocompounds.
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