scholarly journals Structure-based Druggability Assessment of Anti-virulence Targets from Pseudomonas aeruginosa

2019 ◽  
Vol 20 (12) ◽  
pp. 1189-1203 ◽  
Author(s):  
Thamires Q. Froes ◽  
Regina L. Baldini ◽  
Sandor Vajda ◽  
Marcelo S. Castilho
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Drug Development ◽  
In Silico ◽  
Global Economy ◽  
Drug Targets ◽  
Attractive Alternative ◽  
Antibacterial Drug ◽  
Hotspot Analysis ◽  
Combined Use ◽  
Druggable Targets

Antimicrobial Resistance (AMR) represents a serious threat to health and the global economy. However, interest in antibacterial drug development has decreased substantially in recent decades. Meanwhile, anti-virulence drug development has emerged as an attractive alternative to fight AMR. Although several macromolecular targets have been explored for this goal, their druggability is a vital piece of information that has been overlooked. This review explores this subject by showing how structure- based freely available in silico tools, such as PockDrug and FTMap, might be useful for designing novel inhibitors of the pyocyanin biosynthesis pathway and improving the potency/selectivity of compounds that target the Pseudomonas aeruginosa quorum sensing mechanism. The information provided by hotspot analysis, along with binding site features, reveals novel druggable targets (PhzA and PhzS) that remain largely unexplored. However, it also highlights that in silico druggability prediction tools have several limitations that might be overcome in the near future. Meanwhile, anti-virulence drug targets should be assessed by complementary methods, such as the combined use of FTMap/PockDrug, once the consensus druggability classification reduces the risk of wasting resources on undruggable proteins.

scholarly journals FBDD: In-silico STRATEGY TO INHIBIT MPRO ACTIVITY USING DRUGS FROM PREVIOUS OUTBREAKS

2021 ◽  
Vol 9 (4) ◽  
pp. 472-480
Author(s):  
Gauravi N Trivedi ◽  
◽  
Janhavi T Karlekar ◽  
Khushbu Dhimmar ◽  
Hetal kumar Panchal ◽  
...  
Keyword(s):  
Drug Development ◽  
In Silico ◽  
Drug Targets ◽  
Transmission Rate ◽  
Respiratory Illness ◽  
Primary Treatment ◽  
Rational Drug Design ◽  
New Drugs ◽  
Main Protease

Main protease (Mpro) and Spike (S) proteins are said potential drug targets of COVID-19. Pneumonia like respiratory illness caused by SARS-CoV-2 is spreading rapidly due to its replication and transmission rate. Protease is the protein that is involved in both replication and transcription. Since CoV-2 shares, genomic similarity with CoV and MERS-CoV, drugs from previous outbreaks are used as primary treatment of the disease. In-silico drug development strategies are said to be faster and effective than in-vitro with a lesser amount of risk factors. Fragment Based Drug Designing (FBDD), also known as rational drug design in which a potential target protein is selected and docked with a lead-like molecule that eventually leads to drug development. Nine (9) drugs that are currently being used to treat patients of coronavirus were selected in this study from the latest literature review and fragmented as per rules followed by crosslinking of drug fragments using editor tools. These native drugs and synthesized drugs were then docked against the main protease. Results of the study revealed that one of the crosslinked lead-like compounds showed a higher binding affinity (∆G) more than any of the native compounds. Further, the results of this study suggested that the combination of potential drugs can be an effective way to develop new drugs to treat a deadly disease.

scholarly journals FDA Public Workshop Summary: Advancing Animal Models for Antibacterial Drug Development

2020 ◽  
Vol 65 (1) ◽  
pp. e01983-20
Author(s):  
James M. Byrne ◽  
Ursula Waack ◽  
Edward A. Weinstein ◽  
Abhay Joshi ◽  
Simone M. Shurland ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Animal Models ◽  
Drug Development ◽  
Acinetobacter Baumannii ◽  
Drug Administration ◽  
Antibacterial Drug ◽  
Content Type ◽  
Workshop Summary ◽  
Potential Use ◽  
The U.S

ABSTRACTThe U.S. Food and Drug Administration (FDA) hosted a public workshop entitled “Advancing Animal Models for Antibacterial Drug Development” on 5 March 2020. The workshop mainly focused on models of pneumonia caused by Pseudomonas aeruginosa and Acinetobacter baumannii. The program included discussions from academic investigators, industry, and U.S. government scientists. The potential use of mouse, rabbit, and pig models for antibacterial drug development was presented and discussed.

Phytochemicals for drug discovery in Alzheimer’s disease: In silico Advances

2020 ◽  
Vol 26 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Design ◽  
In Silico ◽  
Drug Targets ◽  
Development Process ◽  
Phytochemical Analysis ◽  
Computational Drug Design ◽  
Novel Drugs ◽  
Game Changer

: The search for novel drugs that can prevent or control Alzheimer’s disease has attracted lot of attention from researchers across the globe. Phytochemicals are increasingly being used to provide scaffolds to design drugs for AD. In silico techniques, have proven to be a game-changer in this drug design and development process. In this review, the authors have focussed on current advances in the field of in silico medicine, applied to phytochemicals, to discover novel drugs to prevent or cure AD. After giving a brief context of the etiology and available drug targets for AD, authors have discussed the latest advances and techniques in computational drug design of AD from phytochemicals. Some of the prototypical studies in this area are discussed in detail. In silico phytochemical analysis is a tool of choice for researchers all across the globe and helps integrate chemical biology with drug design.

In Silico Machine Learning Methods in Drug Development

2014 ◽  
Vol 14 (16) ◽  
pp. 1913-1922 ◽  
Author(s):  
Dimitar Dobchev ◽  
Girinath Pillai ◽  
Mati Karelson
Keyword(s):  
Machine Learning ◽  
Drug Development ◽  
In Silico ◽  
Learning Methods ◽  
Machine Learning Methods

Drug repurposing using similarity-based target prediction, docking studies and scaffold hopping of lefamulin

2020 ◽  
Vol 17 ◽  
Author(s):  
Shikha Sharma ◽  
Shweta Sharma ◽  
Vaishali Pathak ◽  
Parwinder Kaur ◽  
Rajesh Kumar Singh
Keyword(s):  
In Silico ◽  
Target Prediction ◽  
Drug Repurposing ◽  
Docking Studies ◽  
Target Protein ◽  
Future Perspective ◽  
Antibacterial Drug ◽  
Scaffold Hopping ◽  
Target Proteins ◽  
Renin Inhibitors

Aim: To investigate and validate the potential target proteins for drug repurposing of newly FDA approved antibacterial drug. Background: Drug repurposing is the process of assigning indications for drugs other than the one(s) that they were initially developed for. Discovery of entirely new indications from already approved drugs is highly lucrative as it minimizes the pipeline of the drug development process by reducing time and cost. In silico driven technologies made it possible to analyze molecules for different target proteins which are not yet explored. Objective: To analyze possible targets proteins for drug repurposing of lefamulin and their validation. Also, in silico prediction of novel scaffolds from lefamulin has been performed for assisting medicinal chemists in future drug design. Methods: A similarity-based prediction tool was employed for predicting target protein and further investigated using docking studies on PDB ID: 2V16. Besides, various in silico tools were employed for prediction of novel scaffolds from lefamulin using scaffold hopping technique followed by evaluation with various in silico parameters viz., ADME, synthetic accessibility and PAINS. Results: Based on the similarity and target prediction studies, renin is found as the most probable target protein for lefamulin. Further, validation studies using docking of lefamulin revealed the significant interactions of lefamulin with the binding pocket of the target protein. Also, three novel scaffolds were predicted using scaffold hopping technique and found to be in the limit to reduce the chances of drug failure in the physiological system during the last stage approval process. Conclusion: To encapsulate the future perspective, lefamulin may assist in the development of the renin inhibitors and, also three possible novel scaffolds with good pharmacokinetic profile can be developed into both as renin inhibitors and for bacterial infections.

Design, Synthesis and In-Vitro Biological Activity of Some New 1,3-Thiazolidine-4-One Derivatives as Chemotherapeutic Agents Using Virtual Screening Strategies

2020 ◽  
Vol 16 ◽  
Author(s):  
Pragya Nayak ◽  
Monica Kachroo
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virtual Screening ◽  
In Silico ◽  
Cancer Cell Line ◽  
Inhibitory Response ◽  
Chemotherapeutic Agents ◽  
Acceptor Site ◽  
Hydrogen Bond Acceptor ◽  
Screening Strategies

: A series of new heteroaryl thiazolidine-4-one derivatives were designed and subjected to in-silico prioritization using various virtual screening strategies. Two series of thiazolidinone derivatives were synthesized and screened for their in-vitro antitubercular, anticancer, antileishmanial and antibacterial (Staphylococcus aureus; Streptococcus pneumonia; Escherichia coli; Pseudomonas aeruginosa) activities. The compounds with electronegative substitutions exhibited positive antitubercular activity, the derivatives possessing a methyl substitution exhibited good inhibitory response against breast cancer cell line MCF-7 while the compounds possessing a hydrogen bond acceptor site like hydroxyl and methoxy substitution in their structures exhibited good in-vitro antileishmanial activity. Some compounds exhibited potent activity against gram positive bacteria Pseudomonas aeruginosa as compared to the standards. Altogether, the designed compounds exhibited good in-vitro anti-infective potential which was in good agreement with the in-silico predictions and they can be developed as important lead molecules for anti-infective and chemotherapeutic drug research.

scholarly journals Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies

PLoS ONE ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. e0156156 ◽  
Author(s):  
Sajad Shahbazi ◽  
Tammanna R. Sahrawat ◽  
Monalisa Ray ◽  
Swagatika Dash ◽  
Dattatreya Kar ◽  
...  
Keyword(s):  
In Silico ◽  
Drug Targets ◽  
Rational Drug ◽  
Anti Inflammatory ◽  
Drug Studies

Evaluation of effectiveness of combined use of COC and topical preparation containing azelaic acid for acne

2021 ◽  
pp. 24-28
Author(s):  
L. S. Kruglova ◽  
N. V. Gryazeva
Keyword(s):  
Azelaic Acid ◽  
Comparable Efficacy ◽  
Antibacterial Drug ◽  
Global Assessment Scale ◽  
Efficiency Assessment ◽  
Combined Use ◽  
Comparison Groups ◽  
Group 2 ◽  
Group 1

The article presents the results of evaluating the effectiveness of the combined use of combined oral contraceptives (COC) and Skinoren cream in severe papular-pustular and moderate nodular-cystic acne.Material and methods. Patients of the first group (n = 11) used COC and an external antibacterial drug two times a day for the treatment of acne. Patients of the second group (n = 12) used COC and an external drug containing azelaic acid (Skinoren) for the treatment of acne two times a day. The duration of follow-up was 6 months. The efficiency assessment was carried out taking into account the dynamics of the indicators of the IGA (Investors Global Assessment) scale. The Manchester Scar Scale (MSS) was used to assess the effectiveness of post-acne correction. In addition, the effectiveness was evaluated based on the results of the mexametry.Results. When evaluating IGA in the comparison groups in patients with severe papulopustular acne and moderate nodular cystic acne, comparable efficacy was noted, but the best results were recorded in the COC + Skinoren group (p < 0.05). No effect and deterioration of the condition were observed in any group. When assessing MSS, the most pronounced changes were observed in patients of group 2, where the combination of COC + Skinoren was used. So, in group 1, the severity of scars decreased by 42.3 %, in group 2 by 48.2 % (p < 0.05). The evaluation of the results of the mexametry showed a more pronounced decrease in the amount of pigment in patients from group 2. When studying the results of the severity of erythema, the dynamics similar to the severity of the pigment was obtained. The best result was registered in group 2 (COC + Skinoren) (p < 0.05).Conclusions. The combined use of COC and Skinoren cream for severe papular-pustular and moderate nodular-cystic acne has proven to be an effective method both in relation to the number of inflammatory and retention elements, and in relation to hyperpigmentation.

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