scholarly journals New Anti SARS-Cov-2 Targets for Quinoline Derivatives Chloroquine and Hydroxychloroquine

2020 ◽  
Vol 21 (16) ◽  
pp. 5856
Author(s):  
Davide Gentile ◽  
Virginia Fuochi ◽  
Antonio Rescifina ◽  
Pio Maria Furneri
Keyword(s):  
Hydrogen Bonding ◽  
Amino Acid ◽  
Hydroxyl Group ◽  
Simulation Methods ◽  
Quinoline Derivatives ◽  
Amino Acid Residues ◽  
Polar Amino Acid ◽  
Health Crisis ◽  
E Protein ◽  
Rapid Spread

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a severe global health crisis. In this paper, we used docking and simulation methods to identify potential targets and the mechanism of action of chloroquine (CQ) and hydroxychloroquine (HCQ) against SARS-CoV-2. Our results showed that both CQ and HCQ influenced the functionality of the envelope (E) protein, necessary in the maturation processes of the virus, due to interactions that modify the flexibility of the protein structure. Furthermore, CQ and HCQ also influenced the proofreading and capping of viral RNA in SARS-CoV-2, performed by nsp10/nsp14 and nsp10/nsp16. In particular, HCQ demonstrated a better energy binding with the examined targets compared to CQ, probably due to the hydrogen bonding of the hydroxyl group of HCQ with polar amino acid residues.

scholarly journals Acid dissociation constants of glycopeptides

1977 ◽  
Vol 163 (1) ◽  
pp. 31-38 ◽  
Author(s):  
B M Austen ◽  
R D Marshall
Keyword(s):  
Amino Acid ◽  
Dissociation Constants ◽  
Acid Dissociation ◽  
Hydroxyl Group ◽  
Amino Acid Residues ◽  
Acid Base ◽  
Titration Curves ◽  
Pka Value ◽  
Hen’S Egg ◽  
Additional Amino Acid

Glycopeptides containing mainly four amino acid residues in the sequence Asn-Leu-Thr-Ser, with small amounts of additional amino acid residues, were isolated from enzymic hydrolysates of hen's-egg albumin. Heterogeneity of the carbohydrate moiety was confirmed. Acid-base titrations showed that the alpha-amino group has a pKa value of 6.43 at 25 degrees C. The standard free engery and entropy changes associated with the ionization at 25 degrees C were 37.2kJ-mol-1 and -0.014kJ-mol-1- K-1 respectively. The complications arising in the interpretation of titration curves of the glycopeptides, which are heterogeneous with respect to the peptide chain, were considered and discussed in the light of the earlier suggestion that the titration curve of the glycopeptide might be interpreted as being due in part to a structure in which the hydroxyl group of the threonine residue is hydrogen-bonded to the beta-aspartamido oxygen atom [Neuberger & Marshall (1968) in Symposium on Foods - Carbohydrates and their Roles (Schultz, H.W., Cain, R.F. & Wrolstad, R.W., eds.), pp. 115-132, Avi Publishing Co., Westport, CT]. It is concluded that either the glycopeptides do not contain a hydrogen bond of that type, or, if they do, that it cannot be recognized by acid-base-titration studies.

Functional analysis of polar amino-acid residues in membrane associated regions of the NHE1 isoform of the mammalian Na+ /H+ exchanger

2001 ◽  
Vol 268 (17) ◽  
pp. 4674-4685 ◽  
Author(s):  
Rakhilya Murtazina ◽  
Brenda J. Booth ◽  
Bonnie L. Bullis ◽  
Dyal N. Singh ◽  
Larry Fliegel
Keyword(s):  
Functional Analysis ◽  
Amino Acid ◽  
Amino Acid Residues ◽  
Polar Amino Acid

scholarly journals Functional role of polar amino acid residues in Na+/H+ exchangers

2001 ◽  
Vol 357 (1) ◽  
pp. 1 ◽  
Author(s):  
Christine A. WIEBE ◽  
Emily R. DiBATTISTA ◽  
Larry FLIEGEL
Keyword(s):  
Amino Acid ◽  
Functional Role ◽  
Amino Acid Residues ◽  
Polar Amino Acid

scholarly journals Fragment Molecular Orbital Based Interaction Analyses on COVID-19 Main Protease - Inhibitor N3 Complex (PDB ID:6LU7)

2020 ◽  
Author(s):  
Ryo Hatada ◽  
Koji Okuwaki ◽  
Yuji Mochizuki ◽  
Kaori Fukuzawa ◽  
Yuto Komeiji ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Amino Acid ◽  
Molecular Orbital ◽  
Interaction Analysis ◽  
Amino Acid Residues ◽  
Inhibitor Molecule ◽  
Fragment Molecular Orbital ◽  
Important Amino Acid ◽  
Main Protease ◽  
Short Period

The worldwide spread of COVID-19 (new coronavirus found in Wuhan in 2019) is an emergent issue to be tackled. In fact, a great amount of works in various fields have been made in rather short period. Here, we report a fragment molecular orbital (FMO) based interaction analysis on a complex between the SARS-CoV-2 main protease (Mpro) and its peptide-like inhibitor N3 (PDB ID: 6LU7). The target inhibitor molecule was segmented into five fragments in order to capture site specific interactions with amino acid residues of the protease. The interaction energies were decomposed into several contributions, and then the characteristics of hydrogen bonding and dispersion stabilization were made clear. Furthermore, the hydration effect was incorporated by the Poisson-Boltzmann (PB) scheme. From the present FMO study, His41, His163, His164, and Glu166 were found to be the most important amino acid residues of Mpro in interacting with the inhibitor, mainly due to hydrogen bonding. A guideline for optimizations of the inhibitor molecule was suggested as well based on the FMO analysis.

scholarly journals Mutation analysis of the cross-reactive epitopes of Japanese encephalitis virus envelope glycoprotein

2012 ◽  
Vol 93 (6) ◽  
pp. 1185-1192 ◽  
Author(s):  
Shyan-Song Chiou ◽  
Yi-Chin Fan ◽  
Wayne D. Crill ◽  
Ruey-Yi Chang ◽  
Gwong-Jen J. Chang
Keyword(s):  
Amino Acid ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Recombinant Expression ◽  
Encephalitis Virus ◽  
Site Directed Mutagenesis ◽  
Amino Acid Residues ◽  
Virus Envelope ◽  
E Protein ◽  
Domain Iii

Group and serocomplex cross-reactive epitopes have been identified in the envelope (E) protein of several flaviviruses and have proven critical in vaccine and diagnostic antigen development. Here, we performed site-directed mutagenesis across the E gene of a recombinant expression plasmid that encodes the Japanese encephalitis virus (JEV) premembrane (prM) and E proteins and produces JEV virus-like particles (VLPs). Mutations were introduced at I135 and E138 in domain I; W101, G104, G106 and L107 in domain II; and T305, E306, K312, A315, S329, S331, G332 and D389 in domain III. None of the mutant JEV VLPs demonstrated reduced activity to the five JEV type-specific mAbs tested. Substitutions at W101, especially W101G, reduced reactivity dramatically with all of the flavivirus group cross-reactive mAbs. The group and JEV serocomplex cross-reactive mAbs examined recognized five and six different overlapping epitopes, respectively. Among five group cross-reactive epitopes, amino acids located in domains I, II and III were involved in one, five and three epitopes, respectively. Recognition by six JEV serocomplex cross-reactive mAbs was reduced by amino acid substitutions in domains II and III. These results suggest that amino acid residues located in the fusion loop of E domain II are the most critical for recognition by group cross-reactive mAbs, followed by residues of domains III and I. The amino acid residues of both domains II and III of the E protein were shown to be important in the binding of JEV serocomplex cross-reactive mAbs.

Isolated Polar Amino Acid Residues Modulate Lipid Binding in the Large Hydrophobic Cavity of CD1d

2016 ◽  
Vol 11 (11) ◽  
pp. 3132-3139 ◽  
Author(s):  
Shinsuke Inuki ◽  
Toshihiko Aiba ◽  
Natsumi Hirata ◽  
Osamu Ichihara ◽  
Daisuke Yoshidome ◽  
...  
Keyword(s):  
Amino Acid ◽  
Lipid Binding ◽  
Amino Acid Residues ◽  
Polar Amino Acid ◽  
Hydrophobic Cavity

Molecular Docking and QSAR Studies of Coumarin Derivatives as NMT Inhibitors: Simple Structural Features as Potential Modulators of Antifungal Activity

2020 ◽  
Vol 17 (10) ◽  
pp. 1293-1308 ◽  
Author(s):  
Sapna Jain Dabade ◽  
Dheeraj Mandloi ◽  
Amritlal Bajaj
Keyword(s):  
Hydrogen Bonding ◽  
Molecular Docking ◽  
Amino Acid ◽  
Antifungal Agents ◽  
External Validation ◽  
Binding Pocket ◽  
Amino Acid Residues ◽  
Statistical Parameters ◽  
Van Der Waals Volume ◽  
Qsar Analysis

Background: Treatments of fungal diseases, including Candidiasis, remain not up to scratch in spite of the mounting catalog of synthetic antifungal agents. These have served as the impetus for investigating new antifungal agents based on natural products. Consequently, genetic algorithm-multiple linear regression (GA-MLR) based QSAR (Quantitative Structure-Activity Relationship) studies of coumarin analogues along with molecular docking were carried out. Methods: Coumarin analogues with their MIC values were used to generate the training and test sets of compounds for QSAR models development; the analogues were also docked into the binding pocket of NMT (MyristoylCoA: protein N-myristoyltransferase). Results and Discussion: The statistical parameters for internal and external validation of QSAR analysis (R2 = 0.830, Q2 = 0.758, R2Pred = 0.610 and R2m overall = 0.683 ), Y Randomization, Ridge trace, VIF, tolerance and model criteria of Golbraikh and Tropsha data illustrate the robustness of the best proposed QSAR model. Most of the analogues bind to the electrostatic, hydrophobic clamp and display hydrogen bonding with amino acid residues of NMT. Interestingly, the most active coumarin analogue (MolDock score of -189.257) was docked deeply within the binding pocket of NMT, thereby displaying hydrogen bonding with Tyr107, Leu451, Leu450, Gln226, Cys393 and Leu394 amino acid residues. Conclusion: The combinations of descriptors from various descriptor subsets in QSAR analysis have highlighted the role of atomic properties such as polarizability and atomic van der Waals volume to explain the inhibitory activity. The models and related information may pave the way for important insight into the designing of putative NMT inhibitors for Candida albicans.

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