Indian Herbs Against COVID-19
The ministry of Ayurvedic, Yoga and Naturopathy, Unani,Sidha and Homeopathy has suggested a possible Ayurvedic treatment for COVID-19.1 The traditional system of herbal medicine focused on cure of the disease and promptly implementing infection control. Potential selected Indian herbs are Ocimum sanctum (Tulsi), Glycyrrhiza glabra (Liquorice), Curcuma domesticaVahl (Turmeric), Tinospora cordifolia (Giloy), Withania somnifera (Ashwagandha), Cinnamon (Dalchini), Shoot of Triticumaestivum Linn. (Wheatgrass), with their antiviral properties to prevent infection and fight against COVID-19 (Table 1). 2
Table 1
Medicinal propertiesof Indian herbs
|
S. No. |
Botanical name |
Active Constituents |
Property |
Medicinal uses |
|
1. |
Tinospora cordifolia |
Berberine, choline, magnoflorine, tinosporin, tinosporic acid |
Anti-bacterial, antioxidant, anti-cancer, anti-viral. Antimalarial |
Chronic fever , anti-HIV, diabetes, immunity enhancer, arthritis etc. 3 |
|
2. |
Withania somnifera |
Withanolides, withaferin A, alkaloids, steroidal lactones, tropine |
Anti-inflammatory, anti-tumor, antistress |
Arthritis, anxiety, insomnia, tumors 4 |
|
3. |
Ocimum sanctum |
Oleanolic acid, ursolic acid, rosmarinic acid, eugenol, Caffeic acid linalool, β-caryophyllene |
Anti-fertility, anticancer, antidiabetic, anti-fungal, antimicrobial |
Bronchitis, bronchial asthma, malaria, diarrhea, skin diseases, etc. 5 |
|
4. |
Shoot of Triticum aestivum Linn |
Potassium, dietary fiber, vitamin A, vitamin C, vitamin E, vitamin K, thiamin, riboflavin, niacin |
Anti-cancer, antiulcer, green blood, |
Cancer prevention, blood purifier, liver disease etc. 6 |
|
5. |
Cinnamon |
Cinnamaldehyde, cinnamate, cinnamic acid, and eugenol |
Anti-inflammatory, antimicrobial, antioxidant, |
Parkinson disease, colon cancer, oral microbiota, etc. 7 |
|
6. |
Curcuma longa domestica Vahl |
Diarylheptanoids, curcuminoids, turmerone, germacrone, atlantone, and zingiberene |
Anti-inflammatory, anti-tumor, antistress, anti-oxidant, |
Body pain, antiseptic, fever, AIDs, cancer etc. 8 |
|
7. |
Glycyrrhiza Glabra |
Glycyrrhizin, isoflaveneglabrene, isoflavaneglabridin |
Anti-inflammatory |
Throat infection, cough infection 9 |
Tulsi
A recent study in India reported that Ocimum sanctum (Tulsi) may be effective in the prevention and management of COVID19. Keeping in view the tremendous pharmacological application of Ocimum sanctum may be utilized to alleviate the symptoms of a variety of diseases. 10 Basil leaves of Oocimum sanctum contains chicoric acid (chicoric acid; also known as dicaffeoyltartaric acid, which is a caffeic acid derivatized with tartaric acid). Rosmarinic acid, chicoric acid and caftaric acid (derivatives of caffeic acid) were identified in fresh basil leaves. Rosmarinic acid was the main phenolic compound found in both leaves and stems. Chicoric acid was not detected in sweet basil stems, although a small amount was present in Thai basil stems. Other cinnamic acid monomers, dimers and trimers were also found in minor quantities in both stems and leaves.11
Computational Studies and Analysis of Viral Protein Structure
Computer assisted drug design (CADD) has been preferred over several years for determining various ligands binding affinity with respect to particular protein.12 It provides significant interactions of identified hits against their biological targets to understand their mode of action.13 Recently, we have performed in silico screening of significant phytochemicals against RNA-dependent RNA Polymerase (RdRp), main protease (Mpro) and membrane protein using molecular docking in search of effective SARS CoV-2 inhibitors motivated by the potential of computational chemistry and in search of potent inhibitors of SARS CoV-2, herein we have performed the virtual screening of total 3 ligands from 2020-01 AsinexEiteSynergy (91,473) and BioDesign (175,851) libraries using AutoDockVina against RdRp and membrane protein using molecular docking followed by their further assessment by formulation development with its evaluation parameter.14
Analysis of protein structure
RNA dependent RNA polymerase (RdRp) co-crystallized with remdesivir having resolution 2.8 Å (PDB ID: 7BV2). This complex contain double-stranded RNA template which was implanted into the central channel of the RdRp where remdesivir was fused into the primer strand covalently. The core component of the viral replication complex is the non-structural proteins (nsp 12) of the RdRp. Second protein selected from protein data bank is Membrane protein (PDB ID: 6M0J) of SARS-CoV-2. 15
Experimental Section
Computational studies for analysis of membrane protein and RNA dependent RNA polymerase
The molecular docking has been performed against selected protein (PDB ID: 7BV2 and 6M0J) using AutoDockVina to evaluate binding affinity of ligand and interactions in the active site. The required three ligands chicoric acid, caftaric acid, rosmarinic acid have been obtained from PubChem database consist of small molecule, which can be easily synthesized in organic chemistry labs.16 This proteins and ligands in PDBQT format have been used for docking process. The binding energy of ligands with protein 7BV2 (RNA and 6M0J have been shown in Figure 2, Figure 3 respectively.
Figure 3
3D interaction of ligands A, B, C with 7BV2 (RdRp). Poses have been generated using Biovia Discovery studio 2020. 17
Collection and Preparation of Data
The 3-dimentonal structure of the SARS-CoV-2 RdRp evaluated through cryo electron microscopy (resolution: 2.8 Å) having antiviral remdesivir as a co-crystallised inhibitor (PDB ID: 7BV2) was obtained from RCSB protein data bank.18 The protein was prepared for further molecular modeling using AutodockVina. All water molecules were deleted along with addition of polar hydrogen atoms and kollman charges to complete the proteins in terms of polarity and charges, respectively. The generation of the receptor grid box around the macromolecule of co-crystallised ligand remdesivir was achieved with the size of 90.768 × 99.896 × 99.788 Å (x,y and z) and the coordinates of centres 70 × 70 ×70 Å (x, y and z). The prepared protein has been kept in PDBQT format which has been further used for the molecular docking. The present docking protocol has been validated by docking of remdesivir using the same and observed with RMSD of less than 1. 19
The Pubchem website contains proteins and ligands. From pubchem we downloaded 3 ligands namely chicoric acid (A), caftaric acid (B) and rosmarinic acid (C). All Ligands have been optimized and converted into PDBQT format using OpenBabel and further used for molecular dockings.
Molecular Docking
Molecular docking with three ligands was performed using the prepared protein using Autodockvina to reveal the binding affinity and interactions of the lingands with RdRp protein (PDB ID: 7BV2) and membrane protein (6M0J). 20 All the ligands were docked on the site using optimized grid box and ten poses per ligand were generated. The docking interaction of hits have been visualized and analyzed using Biovia Discovery studio 2020. 14