The inhibitory effect of some natural bioactive compounds against SARS-CoV-2 main protease: insights from molecular docking analysis and molecular dynamic simulation

The last decade has witnessed a massive increase in the rate of mortalities caused by multidrug-resistant Pseudomonas aeruginosa. Therefore, developing new strategies to control virulence factors and pathogenicity has received much attention. One of these strategies is quorum sensing inhibition (QSI) which was developed to control Pseudomonas infection. This study aims to validate the effect of one of the most used β-lactam antibiotics; cefoperazone (CFP) and its metallic-derivatives on quorum sensing (QS) and virulence factors of P. aeruginosa. Assessment of quorum sensing inhibitory activity of CFP, cefoperazone Iron complex (CFPF) and cefoperazone Cobalt complex (CFPC) was performed by using reporter strain Chromobacterium violaceum ATCC 12472. Minimal inhibitory concentration (MIC) was carried out by the microbroth dilution method. The influence of sub-MICs (1/4 and 1/2 MICs) of CFP, CFPF and CFPC on virulence factors of P. aeruginosa was evaluated. Data was confirmed on the molecular level by RT-PCR. Also, molecular docking analysis was conducted to figure out the possible mechanisms of QSI. CFP, CFPF, and CFPC inhibited violacein pigment production of C. violaceum ATCC 12472. Sub-MICs of CFP (128- 256 μg/mL), and significantly low concentrations of CFPC (0.5- 16 μg/mL) and CFPF (0.5- 64 μg/mL) reduced the production of QS related virulence factors such as pyocyanin, protease, hemolysin and eliminated biofilm assembly by P. aeruginosa standard strains PAO1 and PA14, and P. aeruginosa clinical isolates Ps1, Ps2, and Ps3, without affecting bacterial viability. In addition, CFP, CFPF, and CFPC significantly reduced the expression of lasI and rhlI genes. The molecular docking analysis elucidated that the QS inhibitory effect was possibly caused by the interaction with QS receptors. Both CFPF and CFPC interacted strongly with LasI, LasR and PqsR receptors with a much high ICM scores compared to CFP that could be the cause of elimination of natural ligand binding. Therefore, CFPC and CFPF are potent inhibitors of quorum sensing signaling and virulence factors of P. aeruginosa.

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In Silico Prediction of Novel Inhibitors of SARS-CoV-2 Main Protease through Structure-Based Virtual Screening and Molecular Dynamic Simulation

Pharmaceuticals ◽

10.3390/ph14090896 ◽

2021 ◽

Vol 14 (9) ◽

pp. 896

Author(s):

Sobia Ahsan Halim ◽

Muhammad Waqas ◽

Ajmal Khan ◽

Ahmed Al-Harrasi

Keyword(s):

Virtual Screening ◽

Molecular Dynamic Simulation ◽

Molecular Dynamic ◽

Dynamic Simulation ◽

Interaction Analysis ◽

Severe Disease ◽

Binding Modes ◽

Main Protease ◽

Multiple Structures ◽

Consensus Strategy

The unprecedented pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening global health. SARS-CoV-2 has caused severe disease with significant mortality since December 2019. The enzyme chymotrypsin-like protease (3CLpro) or main protease (Mpro) of the virus is considered to be a promising drug target due to its crucial role in viral replication and its genomic dissimilarity to human proteases. In this study, we implemented a structure-based virtual screening (VS) protocol in search of compounds that could inhibit the viral Mpro. A library of >eight hundred compounds was screened by molecular docking into multiple structures of Mpro, and the result was analyzed by consensus strategy. Those compounds that were ranked mutually in the ‘Top-100’ position in at least 50% of the structures were selected and their analogous binding modes predicted simultaneously in all the structures were considered as bioactive poses. Subsequently, based on the predicted physiological and pharmacokinetic behavior and interaction analysis, eleven compounds were identified as ‘Hits’ against SARS-CoV-2 Mpro. Those eleven compounds, along with the apo form of Mpro and one reference inhibitor (X77), were subjected to molecular dynamic simulation to explore the ligand-induced structural and dynamic behavior of Mpro. The MM-GBSA calculations reflect that eight out of eleven compounds specifically possess high to good binding affinities for Mpro. This study provides valuable insights to design more potent and selective inhibitors of SARS-CoV-2 Mpro.

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Molecular docking analysis of compounds from Lycopersicon esculentum with the insulin receptor to combat type 2 diabetes

Bioinformation ◽

10.6026/97320630016748 ◽

2020 ◽

Vol 16 (10) ◽

pp. 748-752

Author(s):

Anitha Roy ◽

Keyword(s):

Type 2 Diabetes ◽

Molecular Docking ◽

Lycopersicon Esculentum ◽

Insulin Receptor ◽

Bioactive Compounds ◽

Insulin Receptors ◽

Docking Analysis ◽

Molecular Docking Analysis

It is known that tomato (Lycopersicon esculentum) contains bioactive compounds to combat type-2 diabetes. Therefore, it is of interest to document data from the molecular docking analysis of compounds from Lycopersicon esculentum with the insulin receptors to combat type-2 diabetes. We report the binding features of cinnamicacid, chlorogenicacid, gallicacid & glucoside with insulin receptors for further consideration.

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