scholarly journals Recent Developments in New Therapeutic Agents against Alzheimer and Parkinson Diseases: In-Silico Approaches

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2193
Author(s):  
Pedro Cruz-Vicente ◽  
Luís A. Passarinha ◽  
Samuel Silvestre ◽  
Eugenia Gallardo
Keyword(s):  
Clinical Trials ◽  
In Silico ◽  
Symptomatic Relief ◽  
Therapeutic Agents ◽  
Future Perspectives ◽  
Drug Candidates ◽  
Recent Developments ◽  
Progressive Neurodegeneration ◽  
Novel Drug ◽  
Parkinson Diseases

Neurodegenerative diseases (ND), including Alzheimer’s (AD) and Parkinson’s Disease (PD), are becoming increasingly more common and are recognized as a social problem in modern societies. These disorders are characterized by a progressive neurodegeneration and are considered one of the main causes of disability and mortality worldwide. Currently, there is no existing cure for AD nor PD and the clinically used drugs aim only at symptomatic relief, and are not capable of stopping neurodegeneration. Over the last years, several drug candidates reached clinical trials phases, but they were suspended, mainly because of the unsatisfactory pharmacological benefits. Recently, the number of compounds developed using in silico approaches has been increasing at a promising rate, mainly evaluating the affinity for several macromolecular targets and applying filters to exclude compounds with potentially unfavorable pharmacokinetics. Thus, in this review, an overview of the current therapeutics in use for these two ND, the main targets in drug development, and the primary studies published in the last five years that used in silico approaches to design novel drug candidates for AD and PD treatment will be presented. In addition, future perspectives for the treatment of these ND will also be briefly discussed.

scholarly journals PERSPECTIVE INSIGHT AND APPLICATION OF IN-SILICO TOOL AS VIRTUAL SCREENING METHOD FOR LEAD DESIGNING AND DEVELOPMENT

2021 ◽  
Vol 11 (6) ◽  
pp. 16-24
Author(s):  
Hemant U Chikhale
Keyword(s):  
In Silico ◽  
Screening Method ◽  
Lead Discovery ◽  
Environmental Technology ◽  
Lead Structure ◽  
Drug Candidates ◽  
Underlying Principle ◽  
Novel Drug ◽  
Investigative Process ◽  
Specific Illness

Humans are now in a bioinformatics and chemo informatics century, where we can foresee data across domains like as healthcare, the environmental, technology, and public health. The use of information sharing in silico methodologies has impacted sickness administration by predicting the absorption, distribution, metabolism, excretion, and toxicity (ADMET) patterns of synthetic compounds and efficient and environmentally succeeding pharmaceuticals upfront. The purpose of lead discovery and design is to create the appearance of novel drug candidates that can attach to a specific illness cause. The lead investigative process starts with the recognition of the lead structure, which is followed by the synthesis of its analogs and their estimation in order to produce a candidate for lead improvement. The finding of the proper lead exact is the fundamental and primary worked in the traditional lead discovery progression, and the use of computer (in silico) approaches is widely used in lead innovation. A medicinal chemist's passion for building lead structure is piqued by biomolecules, which are often made up of DNA, RNA, and proteins (such as enzymes, receptors, transporters, and ion channels). The underlying principle of such nuts and bolts is noteworthy to be acquainted with their pharmacological implication to the disease under examination. The motive of this review piece of writing is to emphasize several of the in silico methods that are used in lead discovery and to express the applications of these computational methods.

scholarly journals Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyondβ-Amyloid: Insights from Clinical Trials

2014 ◽  
Vol 2014 ◽  
pp. 1-22 ◽  
Author(s):  
Qiutian Jia ◽  
Yulin Deng ◽  
Hong Qing
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Drug Targets ◽  
Neurodegenerative Disorder ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Drug Candidates ◽  
Effective Drugs ◽  
Novel Drug

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with two hallmarks:β-amyloid plagues and neurofibrillary tangles. It is one of the most alarming illnesses to elderly people. No effective drugs and therapies have been developed, while mechanism-based explorations of therapeutic approaches have been intensively investigated. Outcomes of clinical trials suggested several pitfalls in the choice of biomarkers, development of drug candidates, and interaction of drug-targeted molecules; however, they also aroused concerns on the potential deficiency in our understanding of pathogenesis of AD, and ultimately stimulated the advent of novel drug targets tests. The anticipated increase of AD patients in next few decades makes development of better therapy an urgent issue. Here we attempt to summarize and compare putative therapeutic strategies that have completed clinical trials or are currently being tested from various perspectives to provide insights for treatments of Alzheimer’s disease.

scholarly journals Emerging Therapeutic Approaches to Combat COVID-19: Present Status and Future Perspectives

2021 ◽  
Vol 8 ◽  
Author(s):  
Karthik Vivekanandhan ◽  
Poornima Shanmugam ◽  
Hamed Barabadi ◽  
Vigneshwaran Arumugam ◽  
Dharun Daniel Raj Daniel Paul Raj ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Scale Up ◽  
Rapid Expansion ◽  
Future Perspectives ◽  
Therapeutic Approaches ◽  
Vaccine Candidates ◽  
Drug Candidates ◽  
Life Saving ◽  
Immunization Services

Coronavirus disease (COVID-19) has emerged as a fast-paced epidemic in late 2019 which is disrupting life-saving immunization services. SARS-CoV-2 is a highly transmissible virus and an infectious disease that has caused fear among people across the world. The worldwide emergence and rapid expansion of SARS-CoV-2 emphasizes the need for exploring innovative therapeutic approaches to combat SARS-CoV-2. The efficacy of some antiviral drugs such as remdesivir, favipiravir, umifenovir, etc., are still tested against SARS-CoV-2. Additionally, there is a large global effort to develop vaccines for the protection against COVID-19. Because vaccines seem the best solution to control the pandemic but time is required for its development, pre-clinical/clinical trials, approval from FDA and scale-up. The nano-based approach is another promising approach to combat COVID-19 owing to unique physicochemical properties of nanomaterials. Peptide based vaccines emerged as promising vaccine candidates for SARS-CoV-2. The study emphasizes the current therapeutic approaches against SARS-CoV-2 and some of the potential candidates for SARS-CoV-2 treatment which are still under clinical studies for their effectiveness against SARS-CoV-2. Overall, it is of high importance to mention that clinical trials are necessary for confirming promising drug candidates and effective vaccines and the safety profile of the new components must be evaluated before translation of in vitro studies for implementation in clinical use.

scholarly journals Identification of promising drug candidates against Non-Structural Protein 15 (NSP15) from SARS-CoV-2: an in silico assisted drug-repurposing studies

2020 ◽  
Author(s):  
Rameez Jabeer Khan ◽  
Rajat Kumar Jha ◽  
Ekampreet Singh ◽  
Monika Jain ◽  
Gizachew Muluneh Amera ◽  
...  
Keyword(s):  
Free Energy ◽  
In Silico ◽  
Binding Free Energy ◽  
Drug Repurposing ◽  
Md Simulations ◽  
Therapeutic Agents ◽  
Global Dynamics ◽  
Host Immune System ◽  
Structural Protein ◽  
Drug Candidates

<div>The recent COVID-19 pandemic caused by SARS-CoV-2 has recorded a high number of infected people across the globe. The notorious nature of the virus makes it necessary for us to identify promising therapeutic agents in a time-sensitive manner. The current study utilises an <i>in silico</i> based drug repurposing approach to identify potential drug candidates targeting non-structural protein 15 (NSP15), i.e. a uridylate specific endoribonuclease of SARS-CoV-2</div><div>which plays an indispensable role in RNA processing and viral immune evasion from the host immune system. NSP15 was screened against an in-house library of 123 antiviral drugs obtained from the DrugBank database from which three promising drug candidates were identified based on their estimated free energy of binding (<i>ΔG</i>), estimated inhibition constant (<i>Ki</i>), the orientation of drug molecules in the active site and the key interacting residues of</div><div>NSP15. The MD simulations were performed for the selected NSP15-drug complexes along with free protein to mimic on their physiological state. The binding free energies of the selected NSP15-drug complexes were also calculated using the trajectories of MD simulations of NSP15-drug complexes through MM/PBSA (Molecular Mechanics with Poisson-Boltzmann and surface area solvation) approach where NSP15-Simeprevir (-242.559 kJ/mol) and NSP15-Paritaprevir (-149.557 kJ/mol) exhibited the strongest binding affinities. Together with the results of molecular docking, global dynamics, essential dynamics and binding free energy analysis, we propose that Simeprevir and Paritaprevir are promising drug candidates for the inhibition of NSP15 and could act as potential therapeutic agents against SARS-CoV-2.</div>

Discovery of a “Cocktail” of Potential SARS-COV-2 Main Protease Inhibitors through Virtual Screening of Known Chemical Components of Vitex negundo L. (“Lagundi”)

2021 ◽  
Vol 17 ◽  
Author(s):  
Ruel Cayona ◽  
Evelyn Creencia
Keyword(s):  
Clinical Trials ◽  
Virtual Screening ◽  
Medicinal Plants ◽  
In Silico ◽  
Development Program ◽  
Therapeutic Agents ◽  
The Philippines ◽  
Vitex Negundo ◽  
Main Protease ◽  
Donor And Acceptor

Aim: The prevailing crisis caused by the COVID-19 pandemic demands the development of effective therapeutic agents that can be implemented with minimal to zero adverse effects. Background: Vitex negundo L. (VNL) is a medicinal plant with reported efficacy against respiratory diseases and some of the COVID-19 symptoms. Funded by the Department of Science and Technology (DOST), the University of the Philippines – Philippine General Hospital (UP-PGH) is currently conducting clinical trials of VNL and other medicinal plants as adjuvant therapeutic agents against mild cases of COVID-19. The basis for the clinical trials is primarily the pharmacological efficacy of the medicinal plants against respiratory disorders and associated COVID-19 symptoms. Objective: This study assessed the in silico potential of VNL components against SARS-CoV-2 main protease (Mpro), an enzyme that plays an important role in COVID-19, the disease caused by the SARS-CoV-2. Objective: This study assessed the in silico potential of VNL components against SARS-CoV-2 main protease (Mpro), an enzyme that plays an important role in COVID-19, the disease caused by the SARS-CoV-2. Method: Phytochemical mining of VNL components from the literature was conducted. A database consisting of 250 known compounds from different parts of VNL was created and screened against SARS-CoV-2 Mpro using the PyRx virtual screening tool. The most promising components were further subjected to in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses using the SwissADME web server and Toxtree software. Results: Virtual screening revealed that 102 VNL components in the database had comparable to or better binding affinities toward SARS-COV-2 Mpro than known chemical inhibitors (e.g. N3 and carmofur). It was determined that the active site of SARS-CoV-2 Mpro receptor consists of multiple H-donor and acceptor sites; hence, the most stable receptor-ligand complexes are generally formed by VNL ligands that establish effective H-bonding with the SARS-CoV-2 Mpro. The promising components, representing a “cocktail” of potential inhibitors also revealed interesting ADMET properties. Conclusion: This in silico study identified VNL as a potential single source of a cocktail of SARS-CoV-2 Mpro inhibitors and a promising adjuvant therapeutic agent against COVID-19 or its symptoms. Furthermore, the study offers a rationale on phytochemical mining from medicinal plants as a means that can be implemented in the early stage of a drug discovery and development program.

Integrated in Silico Methods for the Design and Optimization of Novel Drug Candidates

Oncology ◽  
2017 ◽  
pp. 434-481
Author(s):  
Nikola Minovski ◽  
Marjana Novič
Keyword(s):  
In Silico ◽  
Comprehensive Overview ◽  
Design And Optimization ◽  
Drug Candidates ◽  
In Silico Drug Design ◽  
Current Trends ◽  
Novel Drugs ◽  
Screening Protocol ◽  
Cost Efficient ◽  
Novel Drug

Although almost fully automated, the discovery of novel, effective, and safe drugs is still a long-term and highly expensive process. Consequently, the need for fleet, rational, and cost-efficient development of novel drugs is crucial, and nowadays the advanced in silico drug design methodologies seem to effectively meet these issues. The aim of this chapter is to provide a comprehensive overview of some of the current trends and advances in the in silico design of novel drug candidates with a special emphasis on 6-fluoroquinolone (6-FQ) antibacterials as potential novel Mycobacterium tuberculosis DNA gyrase inhibitors. In particular, the chapter covers some of the recent aspects of a wide range of in silico drug discovery approaches including multidimensional machine-learning methods, ligand-based and structure-based methodologies, as well as their proficient combination and integration into an intelligent virtual screening protocol for design and optimization of novel 6-FQ analogs.

P1 Receptor Agonists/Antagonists in Clinical Trials - Potential Drug Candidates of the Future

2019 ◽  
Vol 25 (26) ◽  
pp. 2792-2807 ◽  
Author(s):  
Pobitra Borah ◽  
Satyendra Deka ◽  
Raghu Prasad Mailavaram ◽  
Pran Kishore Deb
Keyword(s):  
Clinical Trials ◽  
Biological Activities ◽  
Therapeutic Agents ◽  
Current Status ◽  
Preclinical Studies ◽  
P1 Receptors ◽  
Drug Candidates ◽  
Wide Range ◽  
P1 Receptor ◽  
Novel Therapeutic

Background: Adenosine mediates various physiological and pathological conditions by acting on its four P1 receptors (A1, A2A, A2B and A3 receptors). Omnipresence of P1 receptors and their activation, exert a wide range of biological activities. Thus, its modulation is implicated in various disorders like Parkinson’s disease, asthma, cardiovascular disorders, cancer etc. Hence these receptors have become an interesting target for the researchers to develop potential therapeutic agents. Number of molecules were designed and developed in the past few years and evaluated for their efficacy in various disease conditions. Objective: The main objective is to provide an overview of new chemical entities which have crossed preclinical studies and reached clinical trials stage following their current status and future prospective. Methods: In this review we discuss current status of the drug candidates which have undergone clinical trials and their prospects. Results: Many chemical entities targeting various subtypes of P1 receptors are patented; twenty of them have crossed preclinical studies and reached clinical trials stage. Two of them viz adenosine and regadenoson are approved by the Food and Drug Administration. Conclusion: This review is an attempt to highlight the current status, progress and probable future of P1 receptor ligands which are under clinical trials as promising novel therapeutic agents and the direction in which research should proceed with a view to come out with novel therapeutic agents.

scholarly journals Recent Developments on Therapeutic and Diagnostic Approaches for COVID-19

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Joydeb Majumder ◽  
Tamara Minko
Keyword(s):  
Clinical Trials ◽  
Recent Progress ◽  
Recent Literature ◽  
Antiviral Drugs ◽  
Future Perspectives ◽  
Plasma Therapy ◽  
Public Health Threat ◽  
Recent Developments ◽  
Diagnostic Approaches ◽  
Diagnostics And Therapy

AbstractThe ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious public health threat worldwide with millions of people at risk in a growing number of countries. Though there are no clinically approved antiviral drugs and vaccines for COVID-19, attempts are ongoing for clinical trials of several known antiviral drugs, their combination, as well as development of vaccines in patients with confirmed COVID-19. This review focuses on the latest approaches to diagnostics and therapy of COVID-19. We have summarized recent progress on the conventional therapeutics such as antiviral drugs, vaccines, anti-SARS-CoV-2 antibody treatments, and convalescent plasma therapy which are currently under extensive research and clinical trials for the treatment of COVID-19. The developments of nanoparticle-based therapeutic and diagnostic approaches have been also discussed for COVID-19. We have assessed recent literature data on this topic and made a summary of current development and future perspectives.

scholarly journals CRISPR Screening: Molecular Tools for Studying Virus–Host Interactions

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2258
Author(s):  
Vladimir Chulanov ◽  
Anastasiya Kostyusheva ◽  
Sergey Brezgin ◽  
Natalia Ponomareva ◽  
Vladimir Gegechkori ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Viral Infections ◽  
Whole Genome ◽  
Molecular Tools ◽  
Host Interactions ◽  
Drug Candidates ◽  
Complex Interactions ◽  
Recent Developments ◽  
Novel Drug

CRISPR/Cas is a powerful tool for studying the role of genes in viral infections. The invention of CRISPR screening technologies has made it possible to untangle complex interactions between the host and viral agents. Moreover, whole-genome and pathway-specific CRISPR screens have facilitated identification of novel drug candidates for treating viral infections. In this review, we highlight recent developments in the fields of CRISPR/Cas with a focus on the use of CRISPR screens for studying viral infections and identifying new candidate genes to aid development of antivirals.

scholarly journals Novel Drug Delivery Systems for Rheumatoid Arthritis: An Approach to Better Patient Compliance

2019 ◽  
Vol 12 (1) ◽  
pp. 157-170 ◽  
Author(s):  
Sangeeta Mohanty ◽  
Sthitapragnya Panda ◽  
Aslesha Bhanja ◽  
Abhisek Pal ◽  
Si Sudam Chandra
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Human Life ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
Future Perspectives ◽  
Conventional Drug ◽  
Potential Applications ◽  
Novel Drug

Recent advances in science and technology radically changed the way we detect, treat and prevent different diseases in all aspects of human life. Rheumatoid arthritis (RA) is a chronic, systemic, progressive, autoimmune disease in which the body’s immune system whose major role is to protect the health by attacking foreign bacteria and viruses are mistakenly, attacking the joints resulting in thickened synovium, pannus formation, & destruction of bone, cartilage. Still now researchers are unable to know the exact cause of this disease. However, it is believed that genes and environmental factors play a role in development of RA. In this review, we discuss the Pathophysiology, predictors, & factors involved in pathogenesis of RA. We also discuss the Conventional therapeutic agents for Rheumatoid Arthritis. More importantly, we extensively discuss the emerging novel drug delivery systems (NDDS) like nanoparticles, dendrimers, micelles, microspheres, liposomes, and so on as these are the promising tools having successful applications in overcoming the limitations associated with conventional drug delivery systems. Although several NDDS have been used for various purposes, liposomes have been focused on due to its potential applications in RA diagnosis and therapy. In addition, we discuss the therapeutic effectiveness and challenges for RA by using these novel drug delivery systems. Finally, we conclude by discussing the future perspectives.

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