ABSTRACT
Introduction: Turmeric rhizome (<italic>Cucurma longa</italic> L.) has showed great potential as a traditional drug in folk medicine of several countries. In light of the prominent use of turmeric rhizome in treating both respiratory and viral diseases, we aimed to dock major compounds from the essential oil of turmeric against three key proteins involved in COVID-19 cell entry and replication. Methods: The essential oil of turmeric rhizome was obtained using a hydrodistillation technique, and the chemical characterization of the oil was investigated using GC-MS/GC-FID. Then, main compounds were docked with the key proteins of COVID-19. Results: A total of 26 components were identified in the essential oil extracted from the rhizomes <italic>via</italic> GC-MS/GC-FID. Seven dominant compounds (turmerone (31.4%), ar-turmerone (16.1%), turmerol (14.6%), terpinolene (11.0%), α-zingiberene (5.2%), β-sesquiphellandrene (4.8%), and β-caryophyllene (3.5%)) were docked against COVID-19 main protease, papain-like protease (PLpro), spike protein and 3C-like protease (3CLpro), and the best inhibitor was picked according to the calculated binding affinity and non-bonding interactions with the protein active site. β-sesquiphellandrene and α-zingiberene showed highest besides the same binding affinity towards COVID-19 virus (−6.38 and −6.39kcal/mol, respectively). α-zingiberene was found to bind at the active site of the COVID-19 protein and interacted with different non-bonding interactions, while turmerol showed the highest affinity (−5.78kcal/mol) against CLpro enzyme by binding with Met165, Leu141, Met49, Ser144, Cys145, and Glu166 residues. Conclusion: The essential oil of turmeric harbors a blend of potentially bioactive compounds that may be considered as a good target against COVID-19 virus and warrants further experimental studies. [ABSTRACT FROM AUTHOR] Copyright of Journal of Computational Biophysics & Chemistry is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
In silico techniques helped explore the binding capacities of the SARS-CoV-2 main protease (Mpro) for a series of metalloorganic compounds. Along with small size vanadium complexes a vanadium-containing derivative of the peptide-like inhibitor N3 (N-[(5-methylisoxazol-3-yl)carbonyl]alanyl-l-valyl-N1-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl] methyl }but-2-enyl)-l-leucinamide) was designed from the crystal structure with PDB entry code 6LU7. On theoretical grounds our consensus docking studies evaluated the binding affinities at the hitherto known binding site of Chymotrypsin-like protease (3CLpro) of SARS-CoV-2 for existing and designed vanadium complexes. This main virus protease (Mpro) has a Cys-His dyad at the catalytic site that is characteristic of metal-dependent or metal-inhibited hydrolases. Mpro was compared to the human protein-tyrosine phosphatase 1B (hPTP1B) with a comparable catalytic dyad. HPTP1B is a key regulator at an early stage in the signalling cascade of the insulin hormone for glucose uptake into cells. The vanadium-ligand binding site of hPTP1B is located in a larger groove on the surface of Mpro. Vanadium constitutes a well-known phosphate analogue. Hence, its study offers possibilities to design promising vanadium-containing binders to SARS-CoV-2. Given the favourable physicochemical properties of vanadium nuclei, such organic vanadium complexes could become drugs not only for pharmacotherapy but also diagnostic tools for early infection detection in patients. This work presents the in silico design of a potential lead vanadium compound. It was tested along with 20 other vanadium-containing complexes from the literature in a virtual screening test by docking to inhibit Mpro of SARS-CoV-2.