Identification of naphthyridine and quinoline derivatives as potential Nsp16-Nsp10 inhibitors: a pharmacoinformatics study

Abstract

This research is a recent effort to explore some new heterocyclic compounds as novel and potential nonstructural protein-16-nonstructural protein-10 (Nsp16-Nsp10) inhibitors for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibition. The SARS-CoV-2 is causative agent of coronavirus disease 2019 (COVID-19) pandemic. A set of 58 molecules belongs to the naphthyridine and quinoline derivatives have been recently synthesized and considered for structure-based virtual screening against Nsp16-Nsp10. Molecular docking was virtually performed to screen for anti-SARS-CoV-2 activity against Nsp16-Nsp10. Fourteen out of fifty-eight compounds were exhibited binding affinity higher than co-crystal bound ligand s-adenosylmethionine (SAM) toward Nsp16-Nsp10. Further, the in silico pharmacokinetics assessment was carried out and it was found that two molecules possess the acceptable pharmacokinetic profile, hence considered promising Nsp16-Nsp10 inhibitors. The binding interaction analysis was revealed some crucial binding interactions between the final selected two molecules and ligand-binding amino acid residues of Nsp16-Nsp10 protein. In order to explore the characteristics of the protein-ligand complex and how selected small molecules retained inside the receptor cavity in dynamic states, all-atoms conventional molecular dynamics (MD) simulation was performed. Several factors were obtained from the MD simulation trajectory evidently suggested the potentiality of the molecules and stability of the protein-ligand complex. Finally, the binding affinity of both molecules and SAM was explored through the MM-GBSA approach which explained that both molecules possess strong affection towards the Nsp16-Nsp10. Hence, from the pharmacoinformatics assessment, it can be concluded that both heterocyclic compounds might be crucial for SARS-CoV-2 inhibition, subjected to experimental validation.

Preparation of New Complexes from a Mixture of Aspirin (acetylsalicylic acid), Paracetamol and Methyldopa with Divalent Manganese , Iron, Cobalt, Nickel and Copper, With a Study of Their Physical and Chemical Properties.

“…Tables (2)(3)(4)(5)(6) show the results of the conductivity data, IR spectroscopic, electronic spectra, magnetic moment data , metals% , CHNS and physical properties of complexes.…”

“…Three spin allowed transition to observe in low spin state for Mn(II) ʋ1= 12575, 12567.31 cm-1, ʋ2= 29940.12, 29960.32 cm-1 and ʋ3= 25150.01, 25120.88 cm-1 also another four metals (divalent Iron, Cobalt, Nickel, and Copper) show three bands Table (4), these complexes exhibit six-coordinate octahedral geometry [29,30] .…”

“…Numerous transition metals with mixed drugs molecules complexes show wide-ranging pharmaceutical activity, which place them in several biochemical processes [3] and antivaries agents [4] . Many methods were published for preparing of the mixed ligands metal complexes.…”

Pharmacophore Modelling-Based Drug Repurposing Approaches for SARS-CoV-2 Therapeutics

“…In another study, Tazikeh-Lemeski et al reported the drugs raltegravir and maraviroc, to be effective against nsp 16 ( Tazikeh-Lemeski et al, 2020 ). Bilal et al discovered naphthyridine and quinoline derivatives as possible nsp16-nsp10 inhibitors ( Aldahham et al, 2020 ). However, these computational investigations have not reported our compounds.…”

Deep eutectic solvents (Reline) and Gold Nanoparticles Supported on Titanium Oxide (Au–TiO2) as New Catalysts for synthesis some substituted phenyl(substituted-3-phenyloxiran)methanone Enantioselective Peroxidation

“…Consequently, visible light enabled photocatalytic generation of acyl radicals, tert-butyl hydroperoxide, and cesium carbonate. In fact, it was a technique used to form α,βepoxy ketones by the reaction of a range of styrene and benzaldehydes [14]. Therefore, using the above range as well as conjugated and nonconjugated olefins, epoxyketones were synthesized by the visible-lightdriven hydroacylations and epoxyacylations in water using methylene blue as the photo redox catalyst and persulfate as the oxidant [15].…”