scholarly journals Network Bioinformatics Analysis Provides Insight into Drug Repurposing for COVID-2019

2020 ◽  
Author(s):  
Xu Li ◽  
Jinchao Yu ◽  
Zhiming Zhang ◽  
Jing Ren ◽  
Alex E. Peluffo ◽  
...  
Keyword(s):  
Bioinformatics Analysis ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
Clinical Knowledge ◽  
Phase 3 ◽  
Module Detection ◽  
Novel Drug ◽  
Insight Into ◽  
Old Drugs ◽  
Significant Health

The COVID-2019 disease caused by the SARS-CoV-2 virus (aka 2019-nCoV) has raised significant health concerns in China and worldwide. While novel drug discovery and vaccine studies are long, repurposing old drugs against the COVID-2019 epidemic can help identify treatments, with known preclinical, pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter Phase 3 or 4 or can be used directly in clinical settings. In this study, we presented a novel network based drug repurposing platform to identify potential drugs for the treatment of COVID-2019. We first analysed the genome sequence of SARS-CoV-2 and identified SARS as the closest disease, based on genome similarity between both causal viruses, followed by MERS and other human coronavirus diseases. Using our AutoSeed pipeline (text mining and database searches), we obtained 34 COVID-2019-related genes. Taking those genes as seeds, we automatically built a molecular network for which our module detection and drug prioritization algorithms identified 24 disease-related human pathways, five modules and finally suggested 78 drugs to repurpose. Following manual filtering based on clinical knowledge, we re-prioritized 30 potential repurposable drugs against COVID-2019 (including pseudoephedrine, andrographolide, chloroquine, abacavir, and thalidomide) . We hope that this data can provide critical insights into SARS-CoV-2 biology and help design rapid clinical trials of treatments against COVID-2019.

scholarly journals Network bioinformatics analysis provides insight into drug repurposing for COVID-19

2021 ◽  
pp. 100090
Author(s):  
Xu Li ◽  
Jinchao Yu ◽  
Zhiming Zhang ◽  
Jing Ren ◽  
Alex E Peluffo ◽  
...  
Keyword(s):  
Bioinformatics Analysis ◽  
Drug Repurposing ◽  
Insight Into

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

Old Drugs with New Tricks; Paradigm in Drug Development Pipeline for Alzheimer’s Disease

2020 ◽  
Vol 20 ◽  
Author(s):  
Tanay Dalvi ◽  
Bhaskar Dewangan ◽  
Rudradip Das ◽  
Jyoti Rani ◽  
Suchita Dattatray Shinde ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Development ◽  
Molecular Targets ◽  
Drug Repurposing ◽  
Phase Iii ◽  
Complex Nature ◽  
New Drug ◽  
Development Pipeline ◽  
Old Drugs

: The most common reason behind dementia is Alzheimer’s disease (AD) and it is predicted to be the third lifethreatening disease apart from stroke and cancer for the geriatric population. Till now only four drugs are available in the market for symptomatic relief. The complex nature of disease pathophysiology and lack of concrete evidences of molecular targets are the major hurdles for developing new drug to treat AD. The the rate of attrition of many advanced drugs at clinical stages, makes the de novo discovery process very expensive. Alternatively, Drug Repurposing (DR) is an attractive tool to develop drugs for AD in a less tedious and economic way. Therefore, continuous efforts are being made to develop a new drug for AD by repursing old drugs through screening and data mining. For example, the survey in the drug pipeline for Phase III clinical trials (till February 2019) which has 27 candidates, and around half of the number are drugs which have already been approved for other indications. Although in the past the drug repurposing process for AD has been reviewed in the context of disease areas, molecular targets, there is no systematic review of repurposed drugs for AD from the recent drug development pipeline (2019-2020). In this manuscript, we are reviewing the clinical candidates for AD with emphasis on their development history including molecular targets and the relevance of the target for AD.

Critical Insight into the Attributes of Emerging Novel Coronavirus (COVID-19) in India and Across the World

Coronaviruses ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 49-56
Author(s):  
Gaurav M. Doshi ◽  
Hemen S. Ved ◽  
Ami P. Thakkar
Keyword(s):  
Review Article ◽  
World Health ◽  
Effective Vaccine ◽  
Human Contact ◽  
The World ◽  
Critical Insight ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Insight Into ◽  
Old Drugs

The World Health Organization (WHO) has recently announced the spread of novel coronavirus (nCoV) globally and has declared it a pandemic. The probable source of transmission of the virus, which is from animal to human and human to human contact, has been established. As per the statistics reported by the WHO on 11th April 2020, data has shown that more than sixteen lakh confirmed cases have been identified globally. The reported cases related to nCoV in India have been rising substantially. The review article discusses the characteristics of nCoV in detail with the probability of potentially effective old drugs that may inhibit the virus. The research may further emphasize and draw the attention of the world towards the development of an effective vaccine as well as alternative therapies. Moreover, the article will help to bridge the gap between the new researchers since it’s the current thrust area of research.

scholarly journals Detecting and Profiling Endogenous RNA G-Quadruplexes in the Human Transcriptome

2021 ◽  
Vol 22 (15) ◽  
pp. 8012
Author(s):  
Rongxin Zhang ◽  
Yajun Liu ◽  
Xingxing Zhang ◽  
Ke Xiao ◽  
Yue Hou ◽  
...  
Keyword(s):  
Bioinformatics Analysis ◽  
Biological Functions ◽  
Bioinformatics Pipeline ◽  
The Real ◽  
Human Transcriptome ◽  
Gene Sets ◽  
Nucleic Acid Structures ◽  
Regulatory Functions ◽  
Whole Transcriptome ◽  
Insight Into

G-quadruplexes are the non-canonical nucleic acid structures that are preferentially formed in G-rich regions. This structure has been shown to be associated with many biological functions. Regardless of the broad efforts on DNA G-quadruplexes, we still have limited knowledge on RNA G-quadruplexes, especially in a transcriptome-wide manner. Herein, by integrating the DMS-seq and the bioinformatics pipeline, we profiled and depicted the RNA G-quadruplexes in the human transcriptome. The genes that contain RNA G-quadruplexes in their specific regions are significantly related to immune pathways and the COVID-19-related gene sets. Bioinformatics analysis reveals the potential regulatory functions of G-quadruplexes on miRNA targeting at the scale of the whole transcriptome. In addition, the G-quadruplexes are depleted in the putative, not the real, PAS-strong poly(A) sites, which may weaken the possibility of such sites being the real cleaved sites. In brief, our study provides insight into the potential function of RNA G-quadruplexes in post-transcription.

scholarly journals NOD: a web server to predict New use of Old Drugs to facilitate drug repurposing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tarun Jairaj Narwani ◽  
Narayanaswamy Srinivasan ◽  
Sohini Chakraborti
Keyword(s):  
Chemical Space ◽  
Web Server ◽  
Drug Repurposing ◽  
Cost Effective ◽  
Evolutionary Information ◽  
Cost Effective Alternative ◽  
Similarity Searches ◽  
Old Drugs ◽  
Control Study ◽  
Made In

AbstractComputational methods accelerate the drug repurposing pipelines that are a quicker and cost-effective alternative to discovering new molecules. However, there is a paucity of web servers to conduct fast, focussed, and customized investigations for identifying new uses of old drugs. We present the NOD web server, which has the mentioned characteristics. NOD uses a sensitive sequence-guided approach to identify close and distant homologs of a protein of interest. NOD then exploits this evolutionary information to suggest potential compounds from the DrugBank database that can be repurposed against the input protein. NOD also allows expansion of the chemical space of the potential candidates through similarity searches. We have validated the performance of NOD against available experimental and/or clinical reports. In 65.6% of the investigated cases in a control study, NOD is able to identify drugs more effectively than the searches made in DrugBank. NOD is freely-available at http://pauling.mbu.iisc.ac.in/NOD/NOD/.

Letting Compassion Open the Door: Battered Women's Disclosure to Medical Providers

1995 ◽  
Vol 4 (4) ◽  
pp. 459-465 ◽  
Author(s):  
Heidi M. Bauer ◽  
Michael A. Rodriguez
Keyword(s):  
Healthcare Providers ◽  
Clinical Settings ◽  
Abused Women ◽  
Women Patients ◽  
Medical Providers ◽  
Physically Abused ◽  
Physical Injuries ◽  
Marital Abuse ◽  
Psychiatric Problems ◽  
Significant Health

Domestic violence is an important social problem that strongly impacts the healthcare system. It is estimated that two to four million women are physically abused each year by their husbands, ex-husbands, or boyfriends. Many of these abused women enter the medical system as patients with physical injuries, somatic symptoms, or psychiatric problems. These patients represent a large proportion of women patients in a variety of clinical settings: 22–35% of women presenting to emergency departments, up to 37% of obstetric patients, and over 25% of women seeking primary care. Despite the significant health implications of marital abuse, healthcare providers often fail to identify and treat this problem when signs are present.

scholarly journals Potential 2019-nCoV 3C-like Protease Inhibitors Designed Using Generative Deep Learning Approaches

2020 ◽  
Author(s):  
Alex Zhavoronkov ◽  
Vladimir Aladinskiy ◽  
Alexander Zhebrak ◽  
Bogdan Zagribelnyy ◽  
Victor Terentiev ◽  
...  
Keyword(s):  
Homology Modelling ◽  
Drug Repurposing ◽  
Hiv Protease ◽  
Learning Approaches ◽  
Protein Targets ◽  
Chemical Libraries ◽  
Internal Resources ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Novel Drug

<div> <div> <div> <p>The emergence of the 2019 novel coronavirus (2019-nCoV), for which there is no vaccine or any known effective treatment created a sense of urgency for novel drug discovery approaches. One of the most important 2019-nCoV protein targets is the 3C-like protease for which the crystal structure is known. Most of the immediate efforts are focused on drug repurposing of known clinically-approved drugs and virtual screening for the molecules available from chemical libraries that may not work well. For example, the IC50 of lopinavir, an HIV protease inhibitor, against the 3C-like protease is approximately 50 micromolar. In an attempt to address this challenge, on January 28th, 2020 Insilico Medicine decided to utilize a part of its generative chemistry pipeline to design novel drug-like inhibitors of 2019-nCoV and started generation on January 30th. It utilized three of its previously validated generative chemistry approaches: crystal-derived pocked- based generator, homology modelling-based generation, and ligand-based generation. Novel druglike compounds generated using these approaches are being published at www.insilico.com/ncov-sprint/ and will be continuously updated. Several molecules will be synthesized and tested using the internal resources; however, the team is seeking collaborations to synthesize, test, and, if needed, optimize the published molecules. </p> </div> </div> </div>

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