Spectroscopic, calorimetric and in silico insight into the molecular interactions of Memantine with human transferrin: Implications of Alzheimer's drugs

Abstract OBJECTIVEHistones and resulting nucleosomes occur within DNA regulating gene expression by slowing, pausing, or halting transcriptional machinery. Positions within the genome have been found with higher affinity for the histone octamer than others. Histone/nucleosome repositioning is adjusted via energy dependent remodeling complexes, and a harmonizing array of constellation proteins and molecules. The energy required to create transcriptional environments is created through oxygen intake, nutrient presence, and extracellular movement. In this paper we aim to help facilitate an in silico framework for further experimentation into how partial pressures of oxygen and other gases impact genetic transcription along with extracellular movement and nutrient delivery.RESULTSCell and tissue culture experimentation with biomechanical strain and variable partial pressures of oxygen and other gases can be made into the expression levels of genes such as PH domain leucine-rich repeat-containing protein phosphatase 1 (PHLPP1), and Neuroligin 1 (NLGN1). These genes show in silico to have a higher affinity for a histone octamer binding motif, needing adequate cellular energy to be expressed. Extracellular movement and adequate cellular oxygenation are required to properly reposition nucleosome sequences for transcription.

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In silico screening of phytoconstituents with antiviral activities against SARS-COV-2 main protease, Nsp12 polymerase and Nsp13 helicase proteins

Letters in Drug Design & Discovery ◽

10.2174/1570180818666210317162502 ◽

2021 ◽

Vol 18 ◽

Author(s):

Jainey James ◽

Divya Jyothi ◽

Sneh Priya

Keyword(s):

Antiviral Activity ◽

Molecular Interactions ◽

In Silico ◽

Antiviral Treatment ◽

In Vivo Studies ◽

Main Protease ◽

Hypothesis Model ◽

Antiviral Activities ◽

Pharmacophore Hypothesis

Aims: The present study aim was to analyse the molecular interactions of the phytoconstituents known for their antiviral activity with the SARS-CoV-2 nonstructural proteins such as main protease (6LU7), Nsp12 polymerase (6M71), and Nsp13 helicase (6JYT). The applied in silico methodologies was molecular docking and pharmacophore modeling using Schrodinger software. Methods: The phytoconstituents were taken from PubChem, and SARS-CoV-2 proteins were downloaded from the protein data bank. The molecular interactions, binding energy, ADMET properties and pharmacophoric features were analysed by glide XP, prime MM-GBSA, qikprop and phase application of Schrodinger respectively. The antiviral activity of the selected phytoconstituents was carried out by PASS predictor, online tools. Results: The docking score analysis showed that quercetin 3-rhamnoside (-8.77 kcal/mol) and quercetin 3-rhamnoside (-7.89 kcal/mol) as excellent products to bind with their respective targets such as 6LU7, 6M71 and 6JYT. The generated pharmacophore hypothesis model validated the docking results, confirming the hydrogen bonding interactions of the amino acids. The PASS online tool predicted constituent's antiviral potentials. Conclusion: The docked phytoconstituents showed excellent interactions with the SARS-CoV-2 proteins, and on the outset, quercetin 3-rhamnoside and quercetin 7-rhamnoside have well-interacted with all the three proteins, and these belong to the plant Houttuynia cordata. The pharmacophore hypothesis has revealed the characteristic features responsible for their interactions, and PASS prediction data has supported their antiviral activities. Thus, these natural compounds could be developed as lead molecules for antiviral treatment against SARS-CoV-2. Further in-vitro and in-vivo studies could be carried out to provide better drug therapy.

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