Antiviral phytocompounds “ellagic acid” and “(+)-sesamin” of Bridelia retusa identified as potential inhibitors of SARS-CoV-2 3CL pro using extensive molecular docking, molecular dynamics simulation studies, binding free energy calculations, and bioactivity prediction
Abd Kakhar Umar,James H. Zothantluanga,K. Aswin,Saipul Maulana,Muhammad Sulaiman Zubair,H. Lalhlenmawia,Mithun Rudrapal,Dipak Chetia +7 more
TLDR
In this article , the authors identify natural phytocompounds from Bridelia retusa as potential inhibitors of SARS-CoV-2 3CL pro (PDB ID: 6M2N) using in silico techniques.Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected billions and has killed millions to date. Studies are being carried out to find therapeutic molecules that can potentially inhibit the replication of SARS-CoV-2. 3-chymotrypsin-like protease (3CL pro) involved in the polyprotein cleavage process is believed to be the key target for viral replication, and hence is an attractive target for the discovery of antiviral molecules. In the present study, we aimed to identify natural phytocompounds from Bridelia retusa as potential inhibitors of SARS-CoV-2 3CL pro (PDB ID: 6M2N) using in silico techniques. Molecular docking studies conducted with three different tools in triplicates revealed that ellagic acid (BR6) and (+)-sesamin (BR13) has better binding affinity than the co-crystal inhibitor “3WL” of 6M2N. BR6 and BR13 were found to have a high LD50 value with good bioavailability. 3WL, BR6, and BR13 bind to the same active binding site and interacted with the HIS41-CYS145 catalytic dyad including other crucial amino acids. Molecular dynamics simulation studies revealed stability of protein–ligand complexes as evidenced from root-mean-square deviations, root-mean-square fluctuations (RMSF), protein secondary structure elements, ligand-RMSF, protein–ligand contacts, ligand torsions, and ligand properties. BR6 (−22.3064 kcal/mol) and BR13 (−19.1274 kcal/mol) showed a low binding free energy value. The Bayesian statistical model revealed BR6 and BR13 as better protease inhibitors than 3WL. Moreover, BR6 and BR13 had already been reported to elicit antiviral activities. Therefore, we conclude that ellagic acid and (+)-sesamin as natural antiviral phytocompounds with inhibitory potential against SARS-CoV-2 3CL pro. read more
Citations
More filters
Journal ArticleDOI
Resveratrol and Its Natural Analogues Inhibit RNA Dependant RNA Polymerase (RdRp) of Rhizopus oryzae in Mucormycosis through Computational Investigations
Ismail Celik,Mithun Rudrapal,Pradeep Kumar Yadalam,Sampath Chinnam,Thodur Madapusi Balaji,Saranyaraajan Varadarajan,Johra Khan,Shankargouda Patil,Sanjay G. Walode,Dhiraj V. Panke +9 more
TL;DR: In silico investigation of resveratrol and its two natural analogues, piceatannol and PIC, and 3,5,4'-trimethoxy-trans-stilbene (TMS) for their development as successful antifungal agents targeting the R. O. specific RdRp to combat the deadly mucormycosis is concluded.
Journal ArticleDOI
Identification of 1H-purine-2,6-dione derivative as a potential SARS-CoV-2 main protease inhibitor: molecular docking, dynamic simulations, and energy calculations
TL;DR: Using a test set of recently identified COVID-19 inhibitors, a pharmacophore was developed to screen 20 million drug-like compounds obtained from a freely accessible Zinc database, revealing compound 1 to be a promising SARS-Cov-2 MPro inhibitor suitable for further development.
Journal ArticleDOI
Analgesic and Anti-Inflammatory Potential of Indole Derivatives
Mithun Rudrapal,Ismail Celik,Sampath Chinnam,Ulviye Acar Çevik,Trina Ekawati Tallei,Aatika Nizam,Francis Joy,Magda H. Abdellattif,Sanjay G. Walode +8 more
TL;DR: In this paper , a 2-(2-aminophenoxy)-1-(1H-indol-1-yl)-2-(sübstituephenoxy)-ethan-one derivatives (M1-M4) were analyzed further by thin-layer chromatorgarphy (TLC), melting point, IR, and 1H-NMR.
Journal ArticleDOI
Chestnut Wood Mud as a Source of Ellagic Acid for Dermo-Cosmetic Applications
Federica Moccia,Davide Liberti,Samuele Giovando,Carla Caddeo,Daria Maria Monti,Lucia Panzella,Alessandra Napolitano +6 more
TL;DR: In this paper , a vesicle-based controlled release system for ellagic acid (EA) was proposed, involving the exploitation of chestnut wood mud (CWM), an industrial byproduct from chestnut tannin production, as a largely available and low-cost source of this compound.
Journal ArticleDOI
Computational studies of Bridelia retusa phytochemicals for the identification of promising molecules with inhibitory potential against the spike protein and papain-like protease of SARS-CoV-2
Lima Patowary,Malita Borthakur +1 more
TL;DR: In this article , the authors used molecular docking, protein-ligand interactions, and molecular dynamics simulation techniques to find the most promising phytoconstituents of Bridelia retusa that can inhibit both the proteins.
References
More filters
Journal ArticleDOI
SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules
TL;DR: The new SwissADME web tool is presented that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar are presented.
Journal ArticleDOI
Molecular properties that influence the oral bioavailability of drug candidates.
Daniel F. Veber,Stephen R. Johnson,Hung-Yuan Cheng,Brian R. Smith,Keith W. Ward,Kenneth D. Kopple +5 more
TL;DR: Reduced molecular flexibility, as measured by the number of rotatable bonds, and low polar surface area or total hydrogen bond count are found to be important predictors of good oral bioavailability, independent of molecular weight.
Journal ArticleDOI
Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation
TL;DR: Recent progress on drug metabolism activity profiles, interindividual variability and regulation of expression, and the functional and clinical impact of genetic variation in drug metabolizing P450s are reviewed.
WHO Coronavirus Disease (COVID-19) Dashboard
TL;DR: Globally, as of 10,47am CEST, 28 May 2020, there have been 5,556,679 confirmed cases of COVID-19, including 351,866 deaths, reported to WHO.
Journal ArticleDOI
Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of Drug transport properties
TL;DR: The method, termed topological PSA (TPSA), provides results which are practically identical with the 3D PSA, while the computation speed is 2-3 orders of magnitude faster and may be used for fast bioavailability screening of virtual libraries having millions of molecules.