scholarly journals Drug Repurposing of Approved Drugs Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine and Ergotamine for Combating COVID19

2020 ◽  
Author(s):  
Vishal Mevada ◽  
Pravin Dudhagara ◽  
Himani Gandhi ◽  
Nilam Vaghamshi ◽  
Urvisha Beladiya ◽  
...  
Keyword(s):  
Protein Structures ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Sequential Screening ◽  
Drug Molecules ◽  
Single Target ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Country Office

<p>Pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO Country Office in China on 31 December 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. Currently, there is no Vaccine against COVID-19 pandemic and infection is spreading worldwide vary rapidly there is an exigent requirement of practicable drug treatment. Drug repurposing is one of the most promising approaches for that. Many reports are available with <i>in silico</i> drug repurposing but the majority of them engrossed on a single target. The present study aimed at screening the approved against Covid19 protein and extract the combination of operational comprehensively. A total of 1735 drug molecules against all COVID19 protein structures and sequential screening recognize the better potential of anti-HCV drugs over anti-HIV drugs. The study designated Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine Ergotamin as promising drug candidates for covid19 treatment. The computational analysis also reveled the better potential of proposed drugs over the currently used drug combination for COVID19 drugs. </p>

scholarly journals Drug Repurposing of Approved Drugs Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine and Ergotamine for Combating COVID19

2020 ◽  
Author(s):  
Vishal Mevada ◽  
Pravin Dudhagara ◽  
Himani Gandhi ◽  
Nilam Vaghamshi ◽  
Urvisha Beladiya ◽  
...  
Keyword(s):  
Protein Structures ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Sequential Screening ◽  
Drug Molecules ◽  
Single Target ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Country Office

<p>Pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO Country Office in China on 31 December 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. Currently, there is no Vaccine against COVID-19 pandemic and infection is spreading worldwide vary rapidly there is an exigent requirement of practicable drug treatment. Drug repurposing is one of the most promising approaches for that. Many reports are available with <i>in silico</i> drug repurposing but the majority of them engrossed on a single target. The present study aimed at screening the approved against Covid19 protein and extract the combination of operational comprehensively. A total of 1735 drug molecules against all COVID19 protein structures and sequential screening recognize the better potential of anti-HCV drugs over anti-HIV drugs. The study designated Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine Ergotamin as promising drug candidates for covid19 treatment. The computational analysis also reveled the better potential of proposed drugs over the currently used drug combination for COVID19 drugs. </p>

scholarly journals Drug Repurposing of Approved Drugs Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine and Ergotamine for Combating COVID19

2020 ◽  
Author(s):  
Vishal Mevada ◽  
Pravin Dudhagara ◽  
Himani Gandhi ◽  
Nilam Vaghamshi ◽  
Urvisha Beladiya ◽  
...  
Keyword(s):  
Protein Structures ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Sequential Screening ◽  
Drug Molecules ◽  
Single Target ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Country Office

<p>Pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO Country Office in China on 31 December 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. Currently, there is no Vaccine against COVID-19 pandemic and infection is spreading worldwide vary rapidly there is an exigent requirement of practicable drug treatment. Drug repurposing is one of the most promising approaches for that. Many reports are available with <i>in silico</i> drug repurposing but the majority of them engrossed on a single target. The present study aimed at screening the approved against Covid19 protein and extract the combination of operational comprehensively. A total of 1735 drug molecules against all COVID19 protein structures and sequential screening recognize the better potential of anti-HCV drugs over anti-HIV drugs. The study designated Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine Ergotamin as promising drug candidates for covid19 treatment. The computational analysis also reveled the better potential of proposed drugs over the currently used drug combination for COVID19 drugs. </p>

scholarly journals Potent Synergistic Anti-Human Immunodeficiency Virus (HIV) Effects Using Combinations of the CCR5 Inhibitor Aplaviroc with Other Anti-HIV Drugs

2008 ◽  
Vol 52 (6) ◽  
pp. 2111-2119 ◽  
Author(s):  
Hirotomo Nakata ◽  
Seth M. Steinberg ◽  
Yasuhiro Koh ◽  
Kenji Maeda ◽  
Yoshikazu Takaoka ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Synergistic Effects ◽  
Immunodeficiency Virus ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Nonparametric Statistical ◽  
Anti Hiv ◽  
Ccr5 Inhibitor ◽  
Hiv 1

ABSTRACT Aplaviroc (AVC), an experimental CCR5 inhibitor, potently blocks in vitro the infection of R5-tropic human immunodeficiency virus type 1 (R5-HIV-1) at subnanomolar 50% inhibitory concentrations. Although maraviroc is presently clinically available, further studies are required to determine the role of CCR5 inhibitors in combinations with other drugs. Here we determined anti-HIV-1 activity using combinations of AVC with various anti-HIV-1 agents, including four U.S. Food and Drug Administration-approved drugs, two CCR5 inhibitors (TAK779 and SCH-C) and two CXCR4 inhibitors (AMD3100 and TE14011). Combination effects were defined as synergistic or antagonistic when the activity of drug A combined with B was statistically greater or less, respectively, than the additive effects of drugs A and A combined and drugs B and B combined by using the Combo method, described in this paper, which provides (i) a flexible choice of interaction models and (ii) the use of nonparametric statistical methods. Synergistic effects against R5-HIV-1Ba-L and a 50:50 mixture of R5-HIV-1Ba-L and X4-HIV-1ERS104pre (HIV-1Ba-L/104pre) were seen when AVC was combined with zidovudine, nevirapine, indinavir, or enfuvirtide. Mild synergism and additivity were observed when AVC was combined with TAK779 and SCH-C, respectively. We also observed more potent synergism against HIV-1Ba-L/104pre when AVC was combined with AMD3100 or TE14011. The data demonstrate a tendency toward greater synergism with AVC plus either of the two CXCR4 inhibitors compared to the synergism obtained with combinations of AVC and other drugs, suggesting that the development of effective CXCR4 inhibitors may be important for increasing the efficacies of CCR5 inhibitors.

scholarly journals Drug repurposing using transcriptome sequencing and virtual drug screening in a patient with glioblastoma

2020 ◽  
Author(s):  
Mohamed E. M. Saeed ◽  
Onat Kadioglu ◽  
Henry Johannes Greten ◽  
Adem Yildirim ◽  
Katharina Mayr ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Treatment Options ◽  
Drug Repurposing ◽  
Sequencing Data ◽  
Survival Times ◽  
Chemical Library ◽  
Ki 67 ◽  
Drug Candidates ◽  
Egfr Expression ◽  
Approved Drugs

SummaryBackground Precision medicine and drug repurposing are attractive strategies, especially for tumors with worse prognosis. Glioblastoma is a highly malignant brain tumor with limited treatment options and short survival times. We identified novel BRAF (47-438del) and PIK3R1 (G376R) mutations in a glioblastoma patient by RNA-sequencing. Methods The protein expression of BRAF and PIK3R1 as well as the lack of EGFR expression as analyzed by immunohistochemistry corroborated RNA-sequencing data. The expression of additional markers (AKT, SRC, mTOR, NF-κB, Ki-67) emphasized the aggressiveness of the tumor. Then, we screened a chemical library of > 1500 FDA-approved drugs and > 25,000 novel compounds in the ZINC database to find established drugs targeting BRAF47-438del and PIK3R1-G376R mutated proteins. Results Several compounds (including anthracyclines) bound with higher affinities than the control drugs (sorafenib and vemurafenib for BRAF and PI-103 and LY-294,002 for PIK3R1). Subsequent cytotoxicity analyses showed that anthracyclines might be suitable drug candidates. Aclarubicin revealed higher cytotoxicity than both sorafenib and vemurafenib, whereas idarubicin and daunorubicin revealed higher cytotoxicity than LY-294,002. Liposomal formulations of anthracyclines may be suitable to cross the blood brain barrier. Conclusions In conclusion, we identified novel small molecules via a drug repurposing approach that could be effectively used for personalized glioblastoma therapy especially for patients carrying BRAF47-438del and PIK3R1-G376R mutations.

scholarly journals Computational guided approach for drug repurposing against SARS-CoV-2

2021 ◽  
Author(s):  
Jigisha Anand ◽  
Tanmay Ghildiyal ◽  
Aakanksha Madhwal ◽  
Rishabh Bhatt ◽  
Devvret Verma ◽  
...  
Keyword(s):  
Drug Targets ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Computational Docking ◽  
Drug Candidates ◽  
Docking Tool ◽  
Inhibitory Potential ◽  
Approved Drugs ◽  
Tract Infections

Background: In the current SARS-CoV-2 outbreak, drug repositioning emerges as a promising approach to develop efficient therapeutics in comparison to de novo drug development. The present investigation screened 130 US FDA-approved drugs including hypertension, cardiovascular diseases, respiratory tract infections (RTI), antibiotics and antiviral drugs for their inhibitory potential against SARS-CoV-2. Materials & methods: The molecular drug targets against SARS-CoV-2 proteins were determined by the iGEMDOCK computational docking tool. The protein homology models were generated through SWISS Model workspace. The pharmacokinetics of all the ligands was determined by ADMET analysis. Results: The study identified 15 potent drugs exhibiting significant inhibitory potential against SARS-CoV-2. Conclusion: Our investigation has identified possible repurposed drug candidates to improve the current modus operandi of the treatment given to COVID-19 patients.

scholarly journals Integrated Docking and Enhanced Sampling Based Selection of Repurposing Drugs for SARS-CoV-2 by Targeting Host Dependent Factors

2020 ◽  
Author(s):  
Amit Kumawat ◽  
Sadanandam Namsani ◽  
Debabrata Pramanik ◽  
Sudip Roy ◽  
Jayant K. Singh
Keyword(s):  
Regulatory Protein ◽  
Drug Repurposing ◽  
Md Simulations ◽  
Free Energy Calculations ◽  
High Throughput Analysis ◽  
Drug Candidates ◽  
Global Pandemic ◽  
Therapeutic Uses ◽  
Approved Drugs ◽  
Fda Approved Drugs

Since the onset of global pandemic, the most focused research currently in progress is the development of vaccine candidates and clinical trials of existing FDA approved drugs for other relevant diseases, in order to repurpose them for the COVID-19. Here, we investigate the drug repurposing strategies to counteract the coronavirus infection which involves several potential targetable host proteins involved in viral replication and disease progression. We report the high throughput analysis of literature-derived repurposing drug candidates that can be used to target the genetic regulators known to interact with viral proteins based on experimental and interactome studies. In this work we have performed integrated molecular docking followed by molecular dynamics (MD) simulations and free energy calculations through an expedite insilico process where the number of screened candidates reduces sequentially at every step based on physicochemical information. We elucidate that in addition to the pre-clinical and FDA approved drugs that targets specific regulatory proteins, a range of chemical compounds (Nafamostat, Chloramphenicol, Ponatinib) binds to the other gene transcription and translation regulatory protein with higher affinity and may harbour potential for therapeutic uses.<br>

Drug Discovery by Drug Repurposing: Combating COVID-19 in the 21st Century

2020 ◽  
Vol 20 ◽  
Author(s):  
Nitesh Sanghai ◽  
Kashfia Shafiq ◽  
Geoffrey K. Tranmer
Keyword(s):  
Drug Discovery ◽  
Drug Repurposing ◽  
Compassionate Use ◽  
Drug Candidates ◽  
Working Day ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Day By Day ◽  
Potential Use

: Due to the rapidly developing nature of the current COVID-19 outbreak and its almost immediate humanitarian and economic toll, coronavirus drug discovery efforts have largely focused on generating potential COVID-19 drug candidates as quickly as possible. Globally, scientists are working day and night to find the best possible solution to treat the deadly virus. During the first few months of 2020, the SARS-CoV-2 outbreak quickly developed into a pandemic, with a mortality rate that was increasing at an exponential rate day by day. As a result, scientists have turned to a drug repurposing approach, to rediscover the potential use and benefits of existing approved drugs. Currently, there is no single drug approved by the U.S. Food and Drug Administration (FDA), for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously known as 2019-nCoV) that causes COVID-19. Based on only in-vitro studies, several active drugs are already in the clinical pipeline, made possible by following the compassionate use of medicine protocols. This method of repurposing and the use of existing molecules like Remdesivir (GS-5734), Chloroquine, Hydroxychloroquine, etc. has proven to be a landmark in the field of drug rediscovery. In this review article we will discuss the repurposing of medicines for treating the deadly novel coronavirus (SARS-CoV-2).

scholarly journals Identification of Potential Molecules Against COVID-19 Main Protease Through Structure-Guided Virtual Screening Approach

2020 ◽  
Author(s):  
Lovika Mittal ◽  
Anita Kumari ◽  
Mitul Srivastava ◽  
Mrityunjay Singh ◽  
Shailendra Asthana
Keyword(s):  
Virtual Screening ◽  
Design Method ◽  
Hot Spot ◽  
Drug Repurposing ◽  
Inhibitory Effect ◽  
Drug Molecules ◽  
Main Protease ◽  
Approved Drugs ◽  
Novel Drug

<p>In this work, computer-aided drug design method has been implemented to quickly identify promising drug repurposing candidates against COVID-19 main protease (M<sup>pro</sup>)<sup> </sup>. The world is facing an epidemic and in absence of vaccine or any effective treatment, it has created a sense of urgency for novel drug discovery approaches. We have made an immediate effort by performing virtual screening of clinically approved drugs or molecules under clinical trials against COVID-19 M<sup>pro</sup> to identify potential drug molecules. With given knowledge of this system, N3 and 13B compounds have shown inhibitory effect against COVID-19 M<sup>pro</sup>. Both the compounds were considered as control to filter out the screened molecules. Overall, we have identified six potential compounds, Leupeptin Hemisulphate, Pepstatin A, Nelfinavir , Birinapant, Lypression and Octeotide which have shown the docking energy > -8.0 kcal/mol and MMGBSA > -68.0 kcal/mol. The binding pattern of these compounds suggests that they interacted with key <i>hot-spot</i> residues. Also, their pharmacokinetic annotations and therapeutic importance have indicated that they possess drug-like properties and could pave their way for<i> in-vitro</i> studies. The findings of this work will be significant for structure and pharmacophore-based designing. </p>

scholarly journals Recent Advances in In Silico Target Fishing

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5124 ◽  
Author(s):  
Salvatore Galati ◽  
Miriana Di Stefano ◽  
Elisa Martinelli ◽  
Giulio Poli ◽  
Tiziano Tuccinardi
Keyword(s):  
Drug Discovery ◽  
In Silico ◽  
Drug Targets ◽  
Biological Activities ◽  
Protein Structures ◽  
Drug Repurposing ◽  
Specific Protein ◽  
Protein Targets ◽  
Drug Candidates ◽  
Target Fishing

In silico target fishing, whose aim is to identify possible protein targets for a query molecule, is an emerging approach used in drug discovery due its wide variety of applications. This strategy allows the clarification of mechanism of action and biological activities of compounds whose target is still unknown. Moreover, target fishing can be employed for the identification of off targets of drug candidates, thus recognizing and preventing their possible adverse effects. For these reasons, target fishing has increasingly become a key approach for polypharmacology, drug repurposing, and the identification of new drug targets. While experimental target fishing can be lengthy and difficult to implement, due to the plethora of interactions that may occur for a single small-molecule with different protein targets, an in silico approach can be quicker, less expensive, more efficient for specific protein structures, and thus easier to employ. Moreover, the possibility to use it in combination with docking and virtual screening studies, as well as the increasing number of web-based tools that have been recently developed, make target fishing a more appealing method for drug discovery. It is especially worth underlining the increasing implementation of machine learning in this field, both as a main target fishing approach and as a further development of already applied strategies. This review reports on the main in silico target fishing strategies, belonging to both ligand-based and receptor-based approaches, developed and applied in the last years, with a particular attention to the different web tools freely accessible by the scientific community for performing target fishing studies.

scholarly journals Efficient repositioning of approved drugs as anti-HIV agents using Anti-HIV-Predictor

2016 ◽  
Author(s):  
Shao-Xing Dai ◽  
Huan Chen ◽  
Wen-Xing Li ◽  
Yi-Cheng Guo ◽  
Jia-Qian Liu ◽  
...  
Keyword(s):  
Web Server ◽  
Female Infertility ◽  
Hiv Therapy ◽  
Link Type ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Syncytia Formation ◽  
Anti Hiv Agents ◽  
Anti Hiv

AbstractDevelopment of new, effective and affordable drugs against HIV is urgently needed. In this study, we developed a world’s first web server called Anti-HIV-Predictor (http://bsb.kiz.ac.cn:70/hivpre) for predicting anti-HIV activity of given compounds. This server is rapid and accurate (accuracy >93% and AUC > 0.958). We applied the server to screen 1835 approved drugs for anti-HIV therapy. Totally 67 drugs were predicted to have anti-HIV activity, 25 of which are anti-HIV drugs. Then we experimentally evaluated 35 predicted new anti-HIV compounds by assays of syncytia formation, p24 quantification, cytotoxicity. Finally, we repurposed 7 approved drugs (cetrorelix, dalbavancin, daunorubicin, doxorubicin, epirubicin, idarubicin and valrubicin) as new anti-HIV agents. The original indication of these drugs is involved in a variety of diseases such as female infertility and cancer. Anti-HIV-Predictor and the 7 repurposed anti-HIV agents provided here demonstrate the efficacy of this strategy for discovery of new anti-HIV agents.

Sign in / Sign up

Export Citation Format

Share Document