A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19 (original) (raw)
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Computational guided approach for drug repurposing against SARS-CoV-2
Future Virology, 2021
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.
Scope of repurposed drugs against the potential targets of the latest variants of SARS-CoV-2
Structural Chemistry
The unprecedented outbreak of the severe acute respiratory syndrome (SARS) Coronavirus-2, across the globe, triggered a worldwide uproar in the search for immediate treatment strategies. With no specific drug and not much data available, alternative approaches such as drug repurposing came to the limelight. To date, extensive research on the repositioning of drugs has led to the identification of numerous drugs against various important protein targets of the coronavirus strains, with hopes of the drugs working against the major variants of concerns (alpha, beta, gamma, delta, omicron) of the virus. Advancements in computational sciences have led to improved scope of repurposing via techniques such as structure-based approaches including molecular docking, molecular dynamic simulations and quantitative structure activity relationships, network-based approaches, and artificial intelligence-based approaches with other core machine and deep learning algorithms. This review highlights the various approaches to repurposing drugs from a computational biological perspective, with various mechanisms of action of the drugs against some of the major protein targets of SARS-CoV-2. Additionally, clinical trials data on potential COVID-19 repurposed drugs are also highlighted with stress on the major SARS-CoV-2 targets and the structural effect of variants on these targets. The interaction modelling of some important repurposed drugs has also been elucidated. Furthermore, the merits and demerits of drug repurposing are also discussed, with a focus on the scope and applications of the latest advancements in repurposing.
Scientific Reports
The Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The virus has rapidly spread in humans, causing the ongoing Coronavirus pandemic. Recent studies have shown that, similarly to SARS-CoV, SARS-CoV-2 utilises the Spike glycoprotein on the envelope to recognise and bind the human receptor ACE2. This event initiates the fusion of viral and host cell membranes and then the viral entry into the host cell. Despite several ongoing clinical studies, there are currently no approved vaccines or drugs that specifically target SARS-CoV-2. Until an effective vaccine is available, repurposing FDA approved drugs could significantly shorten the time and reduce the cost compared to de novo drug discovery. In this study we attempted to overcome the limitation of in silico virtual screening by applying a robust in silico drug repurposing strategy. We combined and integrated docking simulations, with molecular dyn...
Computational Chemistry to Repurposing Drugs for the Control of COVID-19
Biologics, 2021
Thus far, in 2021, 219 countries with over 175 million people have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a positive sense, single-stranded RNA virus, and is the causal agent for coronavirus disease (COVID-19). Due to the urgency of the situation, virtual screening as a computational modeling method offers a fast and effective modality of identifying drugs that may be effective against SARS-CoV-2. There has been an overwhelming abundance of molecular docking against SARS-CoV-2 in the last year. Due to the massive volume of computational studies, this systematic review has been created to evaluate and summarize the findings of existing studies. Herein, we report on computational articles of drugs which target, (1) viral protease, (2) Spike protein-ACE 2 interaction, (3) RNA-dependent RNA polymerase, and (4) other proteins and nonstructural proteins of SARS-CoV-2. Based on the studies presented, there are 55 identified natural or d...
Drug repurposing is emerging as a vital approach for identifying known drugs with potential therapeutic indications for COVID-19 disease. This aims to categorize and develop therapeutics by identifying existing approved drugs from drug libraries that can effectively reduce drug development time, cost and safety risk. In the current study, virtual screening of known drugs has been carried out against 24 proteins of SARS-CoV2 (NSP1-NSP16, envelope, membrane, nucleoprotein, spike, ORF3a, ORF6, ORF7a, ORF8, and ORF9b). A total of 4193 approved drugs were screened against these targets using AutoDock Vina. The drugs were classified into active and inactive molecules based on the threshold value of the docking score and the therapeutic indications of top 10 and bottom 10 drugs were analyzed in detail. From the study, it was observed that most of the active drugs have antiviral, antibacterial, anticancer, pain and central nervous system based therapeutic properties. The inactive compounds ...
COVID-19: molecular targets, drug repurposing and new avenues for drug discovery
Memórias do Instituto Oswaldo Cruz, 2020
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infection that may break the healthcare system of several countries. Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. Finally, we also discuss patent protection issues, cost effectiveness and scalability of synthetic routes for some of the most studied repurposing candidates since these are key aspects to meet global demand for COVID-19 treatment.
Discovery of new drug indications for COVID-19: A drug repurposing approach
PLOS ONE
Motivation The outbreak of coronavirus health issues caused by COVID-19(SARS-CoV-2) creates a global threat to public health. Therefore, there is a need for effective remedial measures using existing and approved therapies with proven safety measures has several advantages. Dexamethasone (Pubchem ID: CID0000005743), baricitinib(Pubchem ID: CID44205240), remdesivir (PubchemID: CID121304016) are three generic drugs that have demonstrated in-vitro high antiviral activity against SARS-CoV-2. The present study aims to widen the search and explore the anti-SARS-CoV-2 properties of these potential drugs while looking for new drug indications with optimised benefits via in-silico research. Method Here, we designed a unique drug-similarity model to repurpose existing drugs against SARS-CoV-2, using the anti-Covid properties of dexamethasone, baricitinib, and remdesivir as references. Known chemical-chemical interactions of reference drugs help extract interactive compounds withimprovedanti-S...
Computational and Structural Biotechnology Journal, 2021
The SARS-CoV2 is a highly contagious pathogen that causes COVID-19 disease. It has affected millions of people globally with an average lethality of~3%. There is an urgent need of drugs for the treatment of COVID-19. In the current studies, we have used bioinformatics techniques to screen the FDA approved drugs against nine SARS-CoV2 proteins to identify drugs for repurposing. Additionally, we analyzed if the identified molecules can also affect the human proteins whose expression in lung changed during SARS-CoV2 infection. Targeting such genes may also be a beneficial strategy to curb disease manifestation. We have identified 74 molecules that can bind to various SARS-CoV2 and human host proteins. We experimentally validated our in-silico predictions using vero E6 cells infected with SARS-CoV2 virus. Interestingly, many of our predicted molecules viz. capreomycin, celecoxib, mefloquine, montelukast, and nebivolol showed good activity (IC50) against SARS-CoV2. We hope that these studies may help in the development of new therapeutic options for the treatment of COVID-19.
Identification of Multi-Target Directed Inhibitors of SARS-CoV-2: Drug Repurposing
2021
Background: COVID-19 remains a major global challenge while several drugs identified to ameliorate the syndromes are associated with incessant resistance and lack of prospective potentials to permanently curb the infection. This study is aimed at evaluating the potentials of the existing drug molecules to overcome the viral resistance through multi-target inhibition mechanisms. Methods: Molecular docking and molecular dynamics simulations have been extensively applied to virtually screen 2826 drugs from Selleckem.com library against some key bio-receptors implicated in the SARS-CoV-2 such as the viral nucleocapsid phosphoprotein, the viral spike glycoprotein and the human host ACE2. Results: Five drugs namely D-(+)-Raffinose pentahydrate (1), (-)-Epicatechin gallate (5), 2797 (7), Rutin DAB10 (8) and Hyperoside (9) display higher inhibitory potentials against N-terminal NTD of SARS-CoV-2 (PDB 6M3M) with XP docking scores of -16.20, -11.98, -11.83, -11.81 and -11.41 than remdesivir a...