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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Discovery of ( ±)-3-(1 H -pyrazol-1-yl)-6,7-dihydro-5 H -[1,2,4]triazolo[3,4- b ][1,3,4] thiadiazine derivatives with promising in vitro anticoronavirus and antitumoral activity

A new series of (?±)-(3-(3,5-dimethyl-1H-pyrazol-1-yl)-6-phenyl-6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-7-yl)(phenyl)methanones were efficiently synthesized starting from 4-amino-5-hydrazinyl-4H-1,2,4-triazole-3-thiol 1, acetyl acetone 2, various aromatic and heterocyclic aldehydes 3 and phenacyl bromides 4. All the newly synthesized compounds were tested for their antiviral and antitumoral activity. It was shown that subtle structural variations on the phenyl moiety allowed to tune biological properties toward antiviral or antitumoral activity. Mode-of-action studies revealed that the antitumoral activity was due to inhibition of tubulin polymerization.

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Targeting the cytochrome bc1 complex for drug development in M. tuberculosis: review

Molecular Diversity - The terminal oxidases of the oxidative phosphorylation pathway play a significant role in the survival and growth of M. tuberculosis, targeting these components lead to...     

Study of DNA Light Switch Ru(II) Complexes : Synthesis,Characterization, Photocleavage and Antimicrobial Activity

The three Ru(II) complexes of [Ru(phen)₂dppca]²⁺ (1) [Ru(bpy)₂dppca]²⁺ (2) and [Ru(dmb)₂dppca]²⁺ (3) (where phen = 1,10 phenanthroline, bpy = 2,2-bipyridine, dmb = 2 ,2-dimethyl 2′,2′-bipyridine and polypyridyl ligand containing a single carboxylate functionality dppca ligand (dipyridophenazine-11-carboxylic acid) have been synthesized and characterized. These complexes have been shown to act as promising calf thymus DNA intercalators and a new class of DNA light switches, as evidenced by UV-visible and luminescence titrations with Co²⁺ and EDTA, steady-state emission quenching by [Fe(CN)₆]⁴⁻ and KI, DNA competitive binding with ethidium bromide, viscosity measurements, and DNA melting experiments. The results suggest that 1, 2, and 3 complexes bind to CT-DNA through intercalation and follows the order 1 > 2 > 3. Under irradiation at 365 nm, the three complexes have also been found to promote the photocleavage of plasmid pBR322 DNA.     

Viscosity and Diffusion Effects at the Boundary Surface of Viscous Fluid and Thermoelastic Diffusive Solid Medium

This paper concentrates on the wave motion at the interface of viscous compressible fluid half-space and homogeneous isotropic, generalized thermoelastic diffusive half-space. The wave solutions in both the fluid and thermoelastic diffusive half-spaces have been investigated; and the complex dispersion equation of leaky Rayleigh wave motion have been derived. The phase velocity and attenuation coefficient of leaky Rayleigh waves have been computed from the complex dispersion equation by using the Muller's method. The amplitudes of displacements, temperature change and concentration have been obtained. The effects of viscosity and diffusion on phase velocity and attenuation coefficient of leaky Rayleigh waves motion for different theories of thermoelastic diffusion have been depicted graphically. The magnitude of heat and mass diffusion flux vectors for different theories of thermoelastic diffusion have also been computed and represented graphically.     

Synthesis,structural, electrochemical,and photophysical properties of 4,2′‐thiopyrylogens – a novel class of sensitizers for photoinduced electron transfer reactions

The first three examples of the thioanalog of the 4,2′‐pyrylogen ring system are reported. The influence of the sulfur atom on the structural, electrochemical, and photophysical behavior of this ring system is discussed. In addition, these 4,2′‐thiopyrylogens are compared to their previously reported 4,4′‐isomers and their 4,4′‐ and 4,2′‐oxygen analogs. Copyright © 2010 John Wiley & Sons, Ltd.     

Study of band offsets in InN/Ge heterojunctions

InN layers were directly grown on Ge substrate by plasma-assisted molecular beam epitaxy (PAMBE). The valence band offset (VBO) of wurtzite InN/Ge heterojunction is determined by X-ray photoemission spectroscopy (XPS). The valence band of Ge is found to be 0.18 ± 0.04 eV above that of InN and a type-II heterojunction with a conduction band offset (CBO) of ~ 0.16 eV is found. The accurate determination of the VBO and CBO is important for the design of InN/Ge based electronic devices.     

A study of reaction rates of (n, f ) , (n, \gamma) and (n, 2n) reactions in natU and 232Th by the neutron fluence produced in the graphite set-up (GAMMA-3) irradiated by 2.33 GeV deuteron beam

Spallation neutrons produced in the collision of a 2.33GeV deuteron beam with a large lead target are moderated by a thick graphite block surrounding the target and used to activate the radioactive samples of ^natU and Th put at three different positions, identified as holes “a”, “b” and “c” in the graphite block. Rates of the (n, f), (n, $ \gamma$ and (n, 2n) reactions in the two samples are determined using the gamma spectrometry. The ratios of the experimental reaction rates, R (n, 2n)/R (n, f), for ²³²Th and ^natU are estimated in order to understand the role of the (n, x n) kind of reactions in Accelerator-Driven Sub-critical Systems. For the Th-sample, the ratio is ～ 54 (10)% in the case of hole “a” and ～ 95 (57)% in the case of hole “b” compared to 1.73(20)% for hole “a” and 0.710(9)% for hole “b” in the case of the ^natU sample. Also the ratio of fission rates in uranium to thorium, ^natU (n, f)/ ²³²Th (n, f), is ～ 11.2 (17) in the case of hole “a” and 26.8(85) in hole “b”. Similarly, the ratio ²³⁸U (n, 2n)/ ²³²Th (n, 2n) is 0.36(4) for hole “a” and 0.20(10) for hole “b” showing that ²³²Th is more prone to the (n, x n) reaction than ²³⁸U . All the experimental reaction rates are compared with the simulated ones by generating neutron fluxes at the three holes from MCNPX 2.6c and making use of the LA150 library of cross-sections. The experimental and calculated reaction rates of all the three reactions are in reasonably good agreement. The transmutation power, P _norm as well as P _norm/P _beam of the set-up is estimated using the reaction rates of the (n, $ \gamma$ and (n, 2n) reactions for both the samples in the three holes and compared with some of the results of the “Energy plus Transmutation” set-up and TARC experiment.     

Effect of ion velocity on SHI-induced mixing in Ti/Bi system

Energetic ion beams are proving to be versatile tools for modification and depth profiling of materials. The energy and ion species are the deciding factor in the ion-beam-induced materials modification. Among the various parameters such as electronic energy loss, fluence and heat of mixing, velocity of the ions used for irradiation plays an important role in mixing at the interface. The present study is carried out to find the effect of the velocity of swift heavy ions on interface mixing of a Ti/Bi bilayer system. Ti/Bi/C was deposited on Si substrate at room temperature by an electron gun in a high-vacuum deposition system. Carbon layer is deposited on top to avoid oxidation of the samples. Eighty mega electron volts Au ions and 100?MeV Ag ions with same value of S_e for Ti are used for the irradiation of samples at the fluences 1?×?10¹³–1?×?10¹⁴ ions/cm². Different techniques like Rutherford backscattering spectroscopy, atomic force microscopy and grazing incidence X-ray diffraction were used to characterize the pristine and irradiated samples. The mixing effect is explained in the framework of the thermal spike model. It has been found that the mixing rate is higher for low-velocity Au ions in comparison to high-velocity Ag ions. The result could be explained as due to less energy deposition in thermal spike by high-velocity ions.