Identification of phytocompounds from Houttuynia cordata Thunb. as potential inhibitors for SARS-CoV-2 replication proteins through GC–MS/LC–MS characterization,molecular docking and molecular dynamics simulation

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a massive viral disease outbreak of international concerns. The present study is mainly intended to identify the bioactive phytocompounds from traditional antiviral herb Houttuynia cordata Thunb. as potential inhibitors for three main replication proteins of SARS-CoV-2, namely Main protease (Mpro), Papain-Like protease (PLpro) and ADP ribose phosphatase (ADRP) which control the replication process. A total of 177 phytocompounds were characterized from H. cordata using GC–MS/LC–MS and they were docked against three SARS-CoV-2 proteins (receptors), namely Mpro, PLpro and ADRP using Epic, LigPrep and Glide module of Schrödinger suite 2020-3. During docking studies, phytocompounds (ligand) 6-Hydroxyondansetron (A104) have demonstrated strong binding affinity toward receptors Mpro (PDB ID 6LU7) and PLpro (PDB ID 7JRN) with G-score of???7.274 and???5.672, respectively, while Quercitrin (A166) also showed strong binding affinity toward ADRP (PDB ID 6W02) with G-score -6.788. Molecular Dynamics Simulation (MDS) performed using Desmond module of Schrödinger suite 2020–3 has demonstrated better stability in the ligand–receptor complexes A104-6LU7 and A166-6W02 within 100 ns than the A104-7JRN complex. The ADME-Tox study performed using SwissADMEserver for pharmacokinetics of the selected phytocompounds 6-Hydroxyondansetron (A104) and Quercitrin (A166) demonstrated that 6-Hydroxyondansetron passes all the required drug discovery rules which can potentially inhibit Mpro and PLpro of SARS-CoV-2 without causing toxicity while Quercitrin demonstrated less drug-like properties but also demonstrated as potential inhibitor for ADRP. Present findings confer opportunities for 6-Hydroxyondansetron and Quercitrin to be developed as new therapeutic drug against COVID-19.

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Reply to comment on “Limitation of uranium and thorium traces in charnockite matrix‐PIXE analyses at 3 MeV with Si (Li) detector”

Journal of Radioanalytical and Nuclear Chemistry -     

Structural,magnetic and Mössbauer spectral studies of nanosize aluminum substituted nickel zinc ferrites

Nanosize aluminum substituted nickel zinc ferrites were prepared through aerosol route and characterized using TEM, XRD, magnetic measurements and Mössbauer spectroscopy. The particle size of as obtained samples was found to be ∼10 nm which increases up to ∼85 nm upon annealing at 1200 °C. The unit cell parameter ‘a’ decreases linearly with concentration of aluminum due to the small ionic radius of aluminum. The saturation magnetization for all the samples after annealing at 1200 °C lies in the range 12.9–72.6 emu/g and decreases linearly with concentration of aluminum. Room temperature Mössbauer spectra of all as obtained samples of ferrite compositions exhibited a broad doublet suggesting super paramagnetic nature. This doublet is further resolved into two doublets and assigned to the surface region and internal region atoms of the particles. The samples annealed at 1200 °C show broad sextets, which were fitted with five sextets, indicating different local environment of both tetrahedrally and octahedrally coordinated Fe cation.     

Generalized fractional programming duality: A parametric approach

Using a parametric approach, duality is presented for a minimax fractional programming problem that involves several ratios in the objective function.The first author is thankful to Natural Science and Engineering Research Council of Canada for financial support through Grant A-5319, and the authors are thankful to the anonymous referees for useful suggestions.     

A highly selective and sensitive thorium(IV) PVC membrane electrode based on a dithio-tetraaza macrocyclic compound.

A poly(vinyl chloride)-based membrane composed of dithio-tetraaza macrocyclic compound as a neutral carrier with sodium tetraphenylborate (NaTPB) as an anion excluder and nitrobenzene (NB) as plasticizer was prepared and investigated as a Th(IV)-selective electrode. The electrode exhibits a Nernstian slope of 14.2 +/- 0.3 mV per decade over a wide concentration range (1.0 x 10(-6) to 1.0 x 10(-1) M) with a detection limit of 8.0 x 10(-7) M between pH 3.5 and 9.5. The response time of the sensor is about 10 s and it can be used over a period of 5 months without any divergence in potential. The proposed membrane sensor revealed a good selectivity for Th(IV) over a wide variety of other metal ions and proved to be a better electrode in many respects than those reported in the literature. It was successfully applied as an electrode indicator as well as in the direct determination of thorium ions in standard and real samples.     

Structural changes by sulfoxidation of phenothiazine drugs

Summary The side-chain conformations of psychoactive phenothiazine drugs in crystals are different from those of biologically inactive ring sulfoxide metabolites. This study examines the potential energies, molecular conformations and electrostatic potentials in chlorpromazine, levomepromazine (methotrimeprazine), their sulfoxide metabolites and methoxypromazine. The purpose of the study was to examine the significance of the different crystal conformations of active and inactive phenothiazine derivatives, and to determine why phenothiazine drugs lose most of their biological activity by sulfoxidation. Quantum mechanics and molecular mechanics calculations demonstrated that conformations with the side chain folded over the ring structure had lowest potential energy in vacuo, both in the drugs and in the sulfoxide metabolites. In the sulfoxides, side chain conformations corresponding to the crystal structure of chlorpromazine sulfoxide were characterized by stronger negative electrostatic potentials around the ring system than in the parent drugs. This may weaken the electrostatic interaction of sulfoxide metabolites with negatively charged domains in dopamine receptors, and cause the sulfoxides to be virtually inactive in dopamine receptor binding and related pharmacological tests.