ABSTRACT
Baloxavir marboxil (D1), Baricitinib (D2), Galidesivir (D3), Nitazoxanide (D4), and Oseltamivir (D5) are well‐known performing broad‐spectrum activity against a variety of viruses, thus holding high potentiality towards SARS‐CoV‐2. Quantum properties were examined using density functional theory (DFT). The inhibitability of the drugs towards Angiotensin‐converting enzyme 2 (ACE2) and SARS‐CoV‐2 main protease (6LU7) was evaluated by molecular docking simulation, while their bio‐compatibility was justified by physicochemical properties obtained from QSARIS‐based analysis in reference to Lipinski's rule of five. Quantum analysis suggests that the compounds are highly favourable for intermolecular interaction towards protein structures. Given ligand‐ACE2 systems, the inhibitory effectiveness follows the order D3‐ACE2 > D4‐ACE2 > D2‐ACE2 > D5‐ACE2 > D1‐ACE2;and the corresponding order for ligand‐6LU7 systems is D2‐6LU7 > D4‐6LU7 > D3‐6LU7 > D5‐6LU7 > D1‐6LU7. Galidesivir is predicted as the most effective inhibitor towards both targeted protein structures (DSaverage ‐13.1 kcal.mol‐1) and the most bio‐compatible molecule (Mass 264.9 amu;LogP ‐0.9;Polarisability 26.8 Å3). The theoretical screening suggests all drugs, especially Galidesivir (D3), promising for treatment of SARS‐CoV‐2 infection and encourages in‐related clinical trials.
ABSTRACT
Baloxavir marboxil (D1), Baricitinib (D2), Galidesivir (D3), Nitazoxanide (D4), and Oseltamivir (D5) are well-known performing broad-spectrum activity against a variety of viruses, thus holding high potentiality towards SARS-CoV-2. Quantum properties were examined using density functional theory (DFT). The inhibitability of the drugs towards Angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 main protease (6LU7) was evaluated by molecular docking simulation, while their bio-compatibility was justified by physicochemical properties obtained from QSARIS-based analysis in reference to Lipinski's rule of five. Quantum analysis suggests that the compounds are highly favourable for intermolecular interaction towards protein structures. Given ligand-ACE2 systems, the inhibitory effectiveness follows the order D3-ACE2?>?D4-ACE2?>?D2-ACE2?>?D5-ACE2?>?D1-ACE2;and the corresponding order for ligand-6LU7 systems is D2-6LU7?>?D4-6LU7?>?D3-6LU7?>?D5-6LU7?>?D1-6LU7. Galidesivir is predicted as the most effective inhibitor towards both targeted protein structures (DSaverage -13.1 kcal.mol-1) and the most bio-compatible molecule (Mass 264.9 amu;LogP -0.9;Polarisability 26.8 Å3). The theoretical screening suggests all drugs, especially Galidesivir (D3), promising for treatment of SARS-CoV-2 infection and encourages in-related clinical trials.
ABSTRACT
[This corrects the article DOI: 10.1021/acsomega.0c00772.].
ABSTRACT
[This corrects the article DOI: 10.1021/acsomega.0c00772.].
ABSTRACT
Abstract Carvone and geraniol, well-known by their biological activity, could be promising natural inhibitors for angiotensin-converting enzyme 2 (UniProtKB-Q9BYF1), SARS-CoV-2 main protease (PDB-6LU7), and SARS-CoV-2 spike glycoprotein (PDB-6VSB). Quantum properties of R-(-)-carvone (CA1), S-(+)-carvone (CA2), and trans-geraniol (GE) were examined using density functional theory (DFT). Their inhibitability towards the targeted proteins was evaluated using molecular docking simulation. Lipinski's criteria were utilised to preliminarily screen drug-likeness of the potential inhibitors. Quantum analysis suggests that the compounds are highly favourable for intermolecular interaction towards protein structures. The overall inhibitability of the ligands follows the order GE > CA2 > CA1. Their biologically rigid conformation is given by RMSD registering under 2 Å in any systems. The expected inhibition is explainable by topographical complementarity between the inhibitory aducts. All the candidates are predicted compatible with pharmaceutical applications in physiological environments. Their high polarisability is also conducive to inhibitory activity towards highly polarised protein-structures. The study proposes carvone and geraniol to be promising for natural medication-assisted agents supporting treatment against infection caused by SARS-CoV-2.
ABSTRACT
GC-MS was applied to identify 24 main substances in Melaleuca cajuputi essential oil (TA) extracted from fresh cajeput leaves through steam distilling. The inhibitory capability of active compounds in the TA from Thua Thien Hue, Vietnam over the Angiotensin-Converting Enzyme 2 (ACE2) protein in human body - the host receptor for SARS-CoV-2 and the main protease (PDB6LU7) of the SARS-CoV-2 using docking simulation has been studied herein. The results indicate that the ACE2 and PDB6LU7 proteins were strongly inhibited by 10 out of 24 compounds accounting for 70.9% in the TA. The most powerful anticoronavirus activity is expressed in the order: Terpineol (TA2) ≈ Guaiol (TA5) ≈ Linalool (TA19) > Cineol (TA1) > ß-Selinenol (TA3) > α-Eudesmol (TA4) > γ-Eudesmol (TA7). Interestingly, the synergistic interactions of these 10 substances of the TA exhibit excellent inhibition into the ACE2 and PDB6LU7 proteins. The docking results orient that the natural Melaleuca cajuputi essential oil is considered as a valuable resource for preventing SARS-CoV-2 invasion into human body.
ABSTRACT
Eighteen active substances, including 17 organosulfur compounds found in garlic essential oil (T), were identified by GC-MS analysis. For the first time, using the molecular docking technique, we report the inhibitory effect of the considered compounds on the host receptor angiotensin-converting enzyme 2 (ACE2) protein in the human body that leads to a crucial foundation about coronavirus resistance of individual compounds on the main protease (PDB6LU7) protein of SARS-CoV-2. The results show that the 17 organosulfur compounds, accounting for 99.4% contents of the garlic essential oil, have strong interactions with the amino acids of the ACE2 protein and the main protease PDB6LU7 of SARS-CoV-2. The strongest anticoronavirus activity is expressed in allyl disulfide and allyl trisulfide, which account for the highest content in the garlic essential oil (51.3%). Interestingly, docking results indicate the synergistic interactions of the 17 substances, which exhibit good inhibition of the ACE2 and PDB6LU7 proteins. The results suggest that the garlic essential oil is a valuable natural antivirus source, which contributes to preventing the invasion of coronavirus into the human body.