In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19

• Published in: Computers in biology and medicine Vol. 124; p. 103936
• Main Authors: Vardhan, Seshu, Sahoo, Suban K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01-09-2020; Elsevier Limited
• Subjects: ACE2; ADMET; Amino acids; Angiotensin; Angiotensin-Converting Enzyme 2; Antifungal agents; Antiviral Agents - chemistry; Antiviral Agents - pharmacokinetics; Antiviral Agents - pharmacology; Betacoronavirus - chemistry; Betacoronavirus - drug effects; Binding Sites; Computational Biology; Computer applications; Computer Simulation; Coronavirus; Coronavirus Infections - drug therapy; Coronavirus Infections - virology; Coronavirus RNA-Dependent RNA Polymerase; Coronaviruses; COVID-19; Design optimization; DNA-directed RNA polymerase; Drug development; Drug Evaluation, Preclinical; Drugs; Epidemics; Glycoproteins; Herbal medicine; Host Microbial Interactions - drug effects; Humans; Inhibitors; Limonins - chemistry; Limonins - pharmacokinetics; Limonins - pharmacology; Limonoids; Medicinal plants; Metabolism; Molecular docking; Molecular Docking Simulation; Neem; Olives; Pandemics; Papain; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - chemistry; Peptidyl-Dipeptidase A - drug effects; Permeability; Phytochemicals; Phytochemicals - chemistry; Phytochemicals - pharmacokinetics; Phytochemicals - pharmacology; Pneumonia, Viral - drug therapy; Pneumonia, Viral - virology; Protease; Proteinase; Proteins; RNA polymerase; RNA-Dependent RNA Polymerase - chemistry; RNA-Dependent RNA Polymerase - drug effects; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Simulation; Spike glycoprotein; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - drug effects; Triterpenes - chemistry; Triterpenes - pharmacokinetics; Triterpenes - pharmacology; Triterpenoids; Ursolic acid; Viral Nonstructural Proteins - chemistry; Viral Nonstructural Proteins - drug effects; Viral Proteins - chemistry; Viral Proteins - drug effects; China; COVID-19; Coronavirus; Triterpenoids; ADMET; Molecular docking; Limonoids
• ISSN: 0010-4825; 1879-0534
• DOI: 10.1016/j.compbiomed.2020.103936

Virtual screening of phytochemicals was performed through molecular docking, simulations, in silico ADMET and drug-likeness prediction to identify the potential hits that can inhibit the effects of SARS-CoV-2. Considering the published literature on medicinal importance, 154 phytochemicals with analogous structure from limonoids and triterpenoids were selected to search potential inhibitors for the five therapeutic protein targets of SARS-CoV-2, i.e., 3CLpro (main protease), PLpro (papain-like protease), SGp-RBD (spike glycoprotein-receptor binding domain), RdRp (RNA dependent RNA polymerase) and ACE2 (angiotensin-converting enzyme 2). The in silico computational results revealed that the phytochemicals such as glycyrrhizic acid, limonin, 7-deacetyl-7-benzoylgedunin, maslinic acid, corosolic acid, obacunone and ursolic acid were found to be effective against the target proteins of SARS-CoV-2. The protein-ligand interaction study revealed that these phytochemicals bind with the amino acid residues at the active site of the target proteins. Therefore, the core structure of these potential hits can be used for further lead optimization to design drugs for SARS-CoV-2. Also, the medicinal plants containing these phytochemicals like licorice, neem, tulsi, citrus and olives can be used to formulate suitable therapeutic approaches in traditional medicines.
[Display omitted]
•154 limonoids and triterpenoids were screened computationally to search potential inhibitors for COVID-19.•Phytochemicals were screened by molecular docking, in silico ADMET and drug-likeness prediction.•Docking studies of phytochemicals were performed with five therapeutic protein targets of SARS-CoV-2.•7 potential phytochemicals were proposed as potential hits against the SARS-CoV-2.•Proposed phytochemicals are found mainly in neem, tulsi, citrus, licorice and olives.