Acetaminophen also known as paracetamol, is a drug used in the treatment of pain and fever. It is essentially used for the relief of mild to moderate pain. The presence of phenol and carbonyl oxygen atom enables acetaminophen to behave as a bidentate ligand. The stoichiometry, stability constants and Gibbs free energies of acetaminophen-Zn (II) were determined colorimetrically at 25 and 40 oC using continuous variation and mole  ratio methods. The formation of Zn (II) complex with acetaminophen was studied colorimetrically at an absorption maximum of 630 nm at different temperatures. The data showed that Zn (II) and acetaminophen combine in the molar ratio of 1:1 at pH 7.4 with ionic strength maintained using 0.1M KNO3. Calculated stability constants values were 2.70 x 103 and 2.20 x 103 using continuous variation method and 7.21 x 103 and 7.21 x 103 using mole ratio methods at 25 and 40 oC respectively. Calculated ΔGƟ for the complex were - 1.96 x 104 and -1.98 x 104 J using continuous variation method and -2.2 x 104 J and - 2.31 x 104 J using mole ratio method at 25 and 40 oC respectively. The stability constant and Gibbs free energy results suggested that acetaminophen used in the study is a good chelating agent and can be an efficient antidote in the therapy of Zn (II) overload or poisoning. Keywords: Acetaminophen, Zinc, complex, stability constant, Gibbs free energy.

The use of hydroxychloroquine as SARS-CoV-2 inhibitor is currently being reviewed in various clinical trials.  To exhaustively assess the benefit of hydroxychloroquine in the search for SARS-CoV-2 cure, this paper repositioned hydroxychloroquine as a model for virtual screening on the ZINC database.  Molecular docking studies of 5r7y with the retrieved molecules were performed.  The S-score of the predicted compounds were compared with the reference inhibitor (hydroxychloroquine).  After evaluating their binding energy, five compounds (ZINC52939663, ZINC21291670, ZINC12714071, ZINC40089978 and ZINC15963294) were noticed have to highest binding energy with SARS-CoV-2.  The binding scores of the top five ligands were higher than that of the reference molecule.  The pharmacokinetics, toxicity prediction, drug-likeness and global reactivity assessment of ZINC52939663, present the lead compound as a drug candidate with the probable capacity to inhibit SARS-CoV-2.

This computational study comprises of pharmacophore-base virtual screening of the ZINC database, molecular docking of predicted ligands (pharmacophore agent) against the target protein, SARS-CoV-2 (PDB ID: 5r7y) and the prediction of ADMET descriptors using Swiss ADME and PROTOX-II online web servers.  Meanwhile,  remdesivir, ZINC72392503, ZINC72809903, ZINC06560017, ZINC76101700, ZINC88423098 and ZINC91600695 had a docking scores of -2.0 Kcal/mol, -6.7 Kcal/mol, -6.4 Kcal/mol, -6.0 Kcal/mol, -6.0 Kcal/mol, -6.0 Kcal/mol and-6.0 Kcal/mol respectively.  Meanwhile, ZINC72392503 was selected as the lead molecule and was observed to interact with LUE 27, THR 25, CYS 145, THR 26, SER 46, GLY 143, ASN 142, HIS 163, HIS 41, MET 165, GLU 166, ARG 188, GLN 189, HIS 41, MET 49, SER 46 amino acids.  The ADME descriptor revealed that the lead molecule was soluble, druggable, void of drug-drug interaction that may inhibit essential enzymatic reaction and was noticed to fall into PROTOX-II toxicity class 3.  The lead molecule showed a good affinity for the target protein of SARS-CoV-2, hence, may have a physiological implication that can inhibit a protein responsible for the replication of SARS-CoV-2.

The outbreak of novel coronavirus (SARS-CoV-2) found in Wuhan China is rapidly spreading to all nations of the world.  Currently, there are no approved drugs for the treatment of the novel coronaviral disease.  Meanwhile, repositioning of some antibiotics, antiviral and antimalaria drugs have been employed.  In this study, we used azithromycin as a model drug to virtual screen the ZINC database and the molecules obtained were docked against SARS-CoV-2 protein with PDB code: 5r7y.  The best five ligands with high affinity for the target protein was compared with the reference molecule (Azithromycin).  The docking score for the predicted ligands with high affinity for the target protein include ZINC10635972 (-6.3 kcal/mol), ZINC02651653 (-6.2 kcal/mol), ZINC09728215 (-6.2 kcal/mol), ZINC15003138 (-6.1 kcal/mol), ZINC89836288 (-6.1 kcal/mol) and azithromycin (+28.2 kcal/mol).  The lead molecule (ZINC10635972) was observed to interacted with LUE 141, ASN 142, SER 144, SER 46, GLY 189, GLU 166, MET 165, HIS163, MET 49, HIS 164, PHE 140, GLY 143,THR 25, CYS 145, HIS 41, CYS 44 and THR 45.  Meanwhile, hydrogen bond was predominant in the ZINC10635972-5r7y interaction.  The lead molecule demonstrated good pharmacokinetics properties, drug-like characteristic and moderate chemical reactivity index.  Besides, ZINC10635972 was noticed to fit the class 5 toxicity index.  Hence, ZINC10635972 is a promising compound that should be further examined as drug candidates before clinical evaluation.

Sulfamethoxazole is an antibiotic that is used for the treatment of bacterial infections such as prostatitis, bronchitis and urinary tract infections. It is effective against gram negative and gram positive bacteria. Classical equation has been used in the calculation of stability constant of SulfamethoxazoleCu(II) complex depending on the theoretical explanation of the stoichiometry. The formation of Cu(II) complex with sulfamethoxazole was studied colorimetrically at an absorption maximum of 430 nm at 25, 30, 35 and 40 oC. The data showed that Cu(II) and sulfamethoxazole combine in the molar ratio of 1:2 at pH 7.4 with ionic strength maintained using 0.1M KNO3. Calculated stability constants values were 4.02 x 106 , 2.93 x 106 , 1.37 x 106 and 9.21 x 105 using continuous variation method. Calculated ∆GƟ for the complex were -3.77 x 104 , -3.75 x 104 , -3.62 x 104 and - 3.57 x 104 . The stoichiometry, stability constant and Gibbs free energy results suggested that sulfamethoxazole used in the study is a good chelating agent and can be an efficient antidote in the therapy of Cu(II) overload or poisoning

Pazopanib and axitinib are ATP-competitive inhibitors of the vascular endothelial growth factor receptor. They have shown to be effective and tolerable treatment options for patients with metastatic renal cell cancer and therefore have been used for the control of this disease. Sorafenib is a kinase inhibitor drug approved for the treatment of primary kidney cancer, advanced primary liver cancer, and radioactive iodine resistant advanced thyroid carcinoma. Global energy, binding sites and molecular interactions between pazopanib, sorafenib and axitinib anticancer drugs with vascular endothelial growth factor (VEGF) was probed to find the best binding energy. The structures of pazopanib, axitinib and sorafenib were drawn and constructed using window based program of Arguslab and ACDlab ChemSketch softwares. Docking studies were performed using the Patch dock and Firedock online software packages. The protein data bank (PDB) files of the crystal structure of VEGF were subjected to refinement protocols. The interactive docking method was carried out for all the conformers of each compound in the selected active site. The docked compound was assigned a score according to its fit in the ligand binding pocket (LBP) and its binding mode. The docked complexes were interpreted using Molecular Molegro viewer software. The best binding energy (minimum energy) is-19.15 Kcal/mol,-22.48 Kcal/mol and-22.37 Kcal/mol for pozapanib, sorafenib and axitinid respectively. The negative value of the binding energy shows that pozapanib, sorafenib and axitinib can selectively inhibit VEGF.

The use of hydroxychloroquine as SARS-CoV-2 inhibitor is currently being reviewed in various clinical trials.  To exhaustively assess the benefit of hydroxychloroquine in the search for SARS-CoV-2 cure, this paper repositioned hydroxychloroquine as a model for virtual screening on the ZINC database.  Molecular docking studies of 5r7y with the retrieved molecules were performed.  The S-score of the predicted compounds were compared with the reference inhibitor (hydroxychloroquine).  After evaluating their binding energy, five compounds (ZINC52939663, ZINC21291670, ZINC12714071, ZINC40089978 and ZINC15963294) were noticed have to highest binding energy with SARS-CoV-2.  The binding scores of the top five ligands were higher than that of the reference molecule.  The pharmacokinetics, toxicity prediction, drug-likeness and global reactivity assessment of ZINC52939663, present the lead compound as a drug candidate with the probable capacity to inhibit SARS-CoV-2.

Aims: To investigate the anti-inflammatory activity of Picralima nitida stem bark methanol extract (PNSBE). Study Design: The study was carried out using in vivo (carrageenan-induced paw oedema and egg albumin-induced paw oedema) and in vitro (Human red blood cell (HRBC) membrane stabilization assay) models in rat. Place and Duration of Study: Department of Veterinary Physiology and Pharmacology, Michael Okpara University of Agriculture, Umudike, Abia State, Nigeria from March to July, 2020. Methodology: The extract was used at the doses of 100, 200 and 400 mg/kg while diclofenac (20 mg/kg) was used as the standard reference drug for the in vivo study (carrageenan-induced paw oedema and egg albumin). For the in vitro study (red blood cell haemolysis), the extract was used at the concentrations of 25, 50, 100, 200 and 400 µg/ml while diclofenac 250 µg/ml was used. Results: In the carrageenan-induced paw oedema model, the extract at the doses used and the reference drug significantly (p < 0.05) reduced the paw edema in the rats at 1 hour in a dose dependent manner. Also, in the egg albumin model, the paw oedema of treated rats was significantly (P < 0.05) reduced by PNSBE dose dependently reducing the mean rat paw oedema from 0.99 ± 0.12 to 0.61 ± 0.06 at the first hour. There was also a concentration dependent inhibition of red blood cell haemolysis by the extract in the HRBC membrane stabilization assay. Conclusion: Picralma nitida demonstrated a significant anti-inflammatory activity in this study.