Eur Rev Med Pharmacol Sci. 2021 Dec;25(23):7565-7584. doi: 10.26355/eurrev_202112_27456.

ABSTRACT

OBJECTIVE: With the recent direction in drug repurposing, many approved drugs have been evaluated to assess their effect on the coronavirus or SARS-CoV-2 infection (COVID-19). Driving this path, chloroquine (CQ) has been used in the treatment of malaria and hydroxychloroquine (HCQ) in immunomodulatory and anti-thrombotic action, playing a leading role in initial management of the viral infection.

MATERIALS AND METHODS: Literature search was done using Google Scholar, PubMed and Scopus database using keywords "chloroquine" "SARS-CoV-2" "COVID-19" "mechanism of action" and articles of interest were selected providing evidence of the possible role of CQ in viral infection.

RESULTS: In a bid to understand how and if CQ and HCQ would exert their anti-viral property, mechanistic exegesis was done to review various proposed mechanisms of action. This revealed the inhibition of viral attachment and entry, inhibition of enveloped glycoprotein, inhibition of the development and proliferation of new viral particles as the way they perform their action. There is an interplay between iron metabolism and homeostasis with COVID-19 infection and viral reproduction.

CONCLUSIONS: This study aims to show the functional role of CQ and HCQ, as well as to provide possible mechanistic insight on the role of iron on viral infection, iron starvation and its downstream cellular pathways involving hepcidin and proinflammatory cytokines. The overall aim of providing possible mode of action of CQ and HCQ in the management of COVID-19 infection is exhibited via its anti-viral, anti-inflammatory and anti-thrombotic activities.

PMID:34919258 | DOI:10.26355/eurrev_202112_27456

Front Pharmacol. 2021 Nov 30;12:763649. doi: 10.3389/fphar.2021.763649. eCollection 2021.

ABSTRACT

Background: Previous studies suggested an association of sleep disorders with inflammatory bowel disease (IBD) and indicated that using pharmacological treatments for the modulation of circadian rhythms might prevent IBD pathogenesis or aggravation, but whether the effect of sleep traits on IBD was causal is inconclusive and, therefore, prevents drug repurposing based on the previous studies. We aimed to examine the causal effect of different sleep traits on the pathogenesis of IBD. Methods: Genetic instruments for sleep traits were selected from the largest GWAS studies available in the UK Biobank (n = 449,734) and the 23andMe Research (n = 541,333). A two-sample Mendelian randomization (MR) study was conducted to examine the association of the genetic instruments with IBD (12,882 cases and 21,770 controls), ulcerative colitis (6,968 cases, 20,464 controls), and Crohn's disease (5,956 cases and 14,927 controls). We applied the inverse-variance weighted (IVW) method to estimate causal effects, and we used the weighted median and MR-Egger method for sensitivity analyses. Results: We found that sleep duration (OR, 1.00, 95% CI 1.00-1.01), short sleep duration (OR, 1.07, 95% CI 0.41-2.83), morningness (OR, 1.05, 95% CI 0.87-1.27), daytime napping (OR, 1.64, 95% CI 0.62-4.4), frequent insomnia (OR, 1.17, 95% CI 0.8-1.72), any insomnia (OR, 1.17, 95% CI 0.69-1.97), and snoring (OR, 0.31, 95% CI 0.06-1.54) had no causal effect on IBD, and these sleep traits had no causal effect on ulcerative colitis and Crohn's disease either. Most of the sensitivity analyses showed consistent results with those of the IVW method. Conclusion: Our MR study did not support the causal effect of sleep traits on IBD. Pharmacological modulation of circadian rhythms for the prevention of IBD pathogenesis was unwarranted.

PMID:34916940 | PMC:PMC8669049 | DOI:10.3389/fphar.2021.763649

Nat Commun. 2021 Dec 16;12(1):7327. doi: 10.1038/s41467-021-27547-3.

ABSTRACT

The global disruption caused by the 2020 coronavirus pandemic stressed the supply chain of many products, including pharmaceuticals. Multiple drug repurposing studies for COVID-19 are now underway. If a winning therapeutic emerges, it is unlikely that the existing inventory of the medicine, or even the chemical raw materials needed to synthesize it, will be available in the quantities required. Here, we utilize retrosynthetic software to arrive at alternate chemical supply chains for the antiviral drug umifenovir, as well as eleven other antiviral and anti-inflammatory drugs. We have experimentally validated four routes to umifenovir and one route to bromhexine. In one route to umifenovir the software invokes conversion of six C-H bonds into C-C bonds or functional groups. The strategy we apply of excluding known starting materials from search results can be used to identify distinct starting materials, for instance to relieve stress on existing supply chains.

PMID:34916512 | DOI:10.1038/s41467-021-27547-3

Genome Med. 2021 Dec 16;13(1):189. doi: 10.1186/s13073-021-01000-y.

ABSTRACT

While understanding molecular heterogeneity across patients underpins precision oncology, there is increasing appreciation for taking intra-tumor heterogeneity into account. Based on large-scale analysis of cancer omics datasets, we highlight the importance of intra-tumor transcriptomic heterogeneity (ITTH) for predicting clinical outcomes. Leveraging single-cell RNA-seq (scRNA-seq) with a recommender system (CaDRReS-Sc), we show that heterogeneous gene-expression signatures can predict drug response with high accuracy (80%). Using patient-proximal cell lines, we established the validity of CaDRReS-Sc's monotherapy (Pearson r>0.6) and combinatorial predictions targeting clone-specific vulnerabilities (>10% improvement). Applying CaDRReS-Sc to rapidly expanding scRNA-seq compendiums can serve as in silico screen to accelerate drug-repurposing studies. Availability: https://github.com/CSB5/CaDRReS-Sc .

PMID:34915921 | DOI:10.1186/s13073-021-01000-y

Curr Opin Pharmacol. 2021 Nov 18;62:43-59. doi: 10.1016/j.coph.2021.11.002. Online ahead of print.

ABSTRACT

To face the COVID-19 pandemic, prophylactic vaccines have been developed in record time, but vaccine coverage is still limited, accessibility is not equitable worldwide, and the vaccines are not fully effective against emerging variants. Therefore, therapeutic treatments are urgently needed to control the pandemic and treat vulnerable populations, but despite all efforts made, options remain scarce. However, the knowledge gained during 2020 constitutes an invaluable platform from which to build future therapies. In this review, we highlight the main drug repurposing strategies and achievements made over the first 18 months of the pandemic, but also discuss the antivirals, immunomodulators and drug combinations that could be used in the near future to cure COVID-19.

PMID:34915400 | DOI:10.1016/j.coph.2021.11.002

Front Genet. 2021 Nov 29;12:744170. doi: 10.3389/fgene.2021.744170. eCollection 2021.

ABSTRACT

Drug discovery and repurposing against COVID-19 is a highly relevant topic with huge efforts dedicated to delivering novel therapeutics targeting SARS-CoV-2. In this context, computer-aided drug discovery is of interest in orienting the early high throughput screenings and in optimizing the hit identification rate. We herein propose a pipeline for Ligand-Based Drug Discovery (LBDD) against SARS-CoV-2. Through an extensive search of the literature and multiple steps of filtering, we integrated information on 2,610 molecules having a validated effect against SARS-CoV and/or SARS-CoV-2. The chemical structures of these molecules were encoded through multiple systems to be readily useful as input to conventional machine learning (ML) algorithms or deep learning (DL) architectures. We assessed the performances of seven ML algorithms and four DL algorithms in achieving molecule classification into two classes: active and inactive. The Random Forests (RF), Graph Convolutional Network (GCN), and Directed Acyclic Graph (DAG) models achieved the best performances. These models were further optimized through hyperparameter tuning and achieved ROC-AUC scores through cross-validation of 85, 83, and 79% for RF, GCN, and DAG models, respectively. An external validation step on the FDA-approved drugs collection revealed a superior potential of DL algorithms to achieve drug repurposing against SARS-CoV-2 based on the dataset herein presented. Namely, GCN and DAG achieved more than 50% of the true positive rate assessed on the confirmed hits of a PubChem bioassay.

PMID:34912370 | PMC:PMC8667578 | DOI:10.3389/fgene.2021.744170

Genome Med. 2021 Dec 16;13(1):187. doi: 10.1186/s13073-021-01001-x.

ABSTRACT

We present Beyondcell, a computational methodology for identifying tumour cell subpopulations with distinct drug responses in single-cell RNA-seq data and proposing cancer-specific treatments. Our method calculates an enrichment score in a collection of drug signatures, delineating therapeutic clusters (TCs) within cellular populations. Additionally, Beyondcell determines the therapeutic differences among cell populations and generates a prioritised sensitivity-based ranking in order to guide drug selection. We performed Beyondcell analysis in five single-cell datasets and demonstrated that TCs can be exploited to target malignant cells both in cancer cell lines and tumour patients. Beyondcell is available at: https://gitlab.com/bu_cnio/beyondcell .

PMID:34911571 | DOI:10.1186/s13073-021-01001-x

Transl Oncol. 2021 Dec 12;16:101303. doi: 10.1016/j.tranon.2021.101303. Online ahead of print.

ABSTRACT

Sertraline hydrochloride is a first-line antidepressant with potential antineoplastic properties because of its structural similarity with other drugs capable to inhibit the translation-controlled tumor protein (TCTP), a biomolecule involved in cell proliferation. Recent studies suggest it could be repositioned for cancer treatment. In this review, we systematically map the findings that repurpose sertraline as an antitumoral agent, including the mechanisms of action that support this hypotesis. From experimental in vivo and in vitro tumor models of thirteen different types of neoplasms, three mechanisms of action are proposed: apoptosis, autophagy, and drug synergism. The antidepressant is able to inhibit TCTP, modulate chemotherapeutical resistance and exhibit proper cytotoxicity, resulting in reduced cell counting (in vitro) and shrunken tumor masses (in vivo). A mathematical equation determined possible doses to be used in human beings, supporting that sertraline could be explored in clinical trials as a TCTP-inhibitor.

PMID:34911014 | DOI:10.1016/j.tranon.2021.101303

OMICS. 2021 Dec 15. doi: 10.1089/omi.2021.0195. Online ahead of print.

ABSTRACT

Gastric cancer (GC) is a prevalent disease worldwide with high mortality and poor treatment success. Early diagnosis of GC and forecasting of its prognosis with the use of biomarkers are directly relevant to achieve both personalized/precision medicine and innovation in cancer therapeutics. Gene expression signatures offer one of the promising avenues of research in this regard, as well as guiding drug repurposing analyses in cancers. Using publicly accessible gene expression datasets from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA), we report here original findings on co-expressed gene modules that are differentially expressed between 133 GC samples and 46 normal tissues, and thus hold potential for novel diagnostic candidates for GC. Furthermore, we found two co-expressed gene modules were significantly associated with poor survival outcomes revealed by survival analysis of the RNA-Seq TCGA datasets. We identified STAT6 (signal transducer and activator of transcription 6) as a key regulator of the identified gene modules. Finally, potential therapeutic drugs that may target and reverse the expression of the identified altered gene modules examined for drug repurposing analyses and the unraveled compounds were further investigated in the literature by the text mining method. Accordingly, we found several repurposed drug candidates, including Trichostatin A, Vorinostat, Parthenolide, Panobinostat, Brefeldin A, Belinostat, and Danusertib. Through text mining analysis and literature search validation, Belinostat and Danusertib were suggested as possible novel drug candidates for GC treatment. These findings collectively inform multiple aspects of GC medical management, including its precision diagnosis, forecasting of possible outcomes, and drug repurposing for innovation in GC medicines in the future.

PMID:34910889 | DOI:10.1089/omi.2021.0195

Curr Res Pharmacol Drug Discov. 2021 Jun 9;2:100041. doi: 10.1016/j.crphar.2021.100041. eCollection 2021.

ABSTRACT

Psoriasis is a chronic inflammatory autoimmune condition manifested by the hyperproliferation of keratinocytes with buildup of inflammatory red patches and scales on skin surfaces. The available treatment options for the management of psoriasis have various drawbacks, and the clinical need for effective therapeutics for this disease remain unmet; therefore, the approaches of drug repurposing or drug repositioning could potentially be used for treating indications of psoriasis. The undiscovered potential of drug repurposing or repositioning compensates for the limitations and hurdles in drug discovery and drug development processes. Drugs initially approved for other indications, including anticancer, antidiabetic, antihypertensive, and anti-arthritic activities, are being investigated for their potential in psoriasis management as a new therapeutic indication by using repurposing strategies. This article envisages the potential of various therapeutics for the management of psoriasis.

PMID:34909670 | PMC:PMC8663928 | DOI:10.1016/j.crphar.2021.100041

Curr Res Pharmacol Drug Discov. 2021 Apr 8;2:100022. doi: 10.1016/j.crphar.2021.100022. eCollection 2021.

ABSTRACT

Neurodegenerative diseases (ND) are of vast origin which are characterized by gradual progressive loss of neurons in the brain region. ND can be classified according to the clinical symptoms present (e.g. Cognitive decline, hyperkinetic, and hypokinetic movements disorder) or by the pathological protein deposited (e.g., Amyloid, tau, Alpha-synuclein, TDP-43). Alzheimer's disease preceded by Parkinson's is the most prevalent form of ND world-wide. Multiple factors like aging, genetic mutations, environmental factors, gut microbiota, blood-brain barrier microvascular complication, etc. may increase the predisposition towards ND. Genetic mutation is a major contributor in increasing the susceptibility towards ND, the concept of one disease-one gene is obsolete and now multiple genes are considered to be involved in causing one particular disease. Also, the involvement of multiple pathological mechanisms like oxidative stress, neuroinflammation, mitochondrial dysfunction, etc. contributes to the complexity and makes them difficult to be treated by traditional mono-targeted ligands. In this aspect, the Poly-pharmacological drug approach which targets multiple pathological pathways at the same time provides the best way to treat such complex networked CNS diseases. In this review, we have provided an overview of ND and their pathological origin, along with a brief description of various genes associated with multiple diseases like Alzheimer's, Parkinson's, Multiple sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Huntington's and a comprehensive detail about the Poly-pharmacology approach (MTDLs and Fixed-dose combinations) along with their merits over the traditional single-targeted drug is provided. This review also provides insights into current repurposing strategies along with its regulatory considerations.

PMID:34909657 | PMC:PMC8663985 | DOI:10.1016/j.crphar.2021.100022

Curr Res Pharmacol Drug Discov. 2020 Dec 31;2:100012. doi: 10.1016/j.crphar.2020.100012. eCollection 2021.

ABSTRACT

Neurodegenerative disorders which affects a larger population pose a great clinical challenge. These disorders impact the quality of life of an individual by damaging the neurons, which are the unit cells of the brain. Clinicians are faced with the grave challenge of inhibiting the progression of these diseases as available treatment options fail to meet the clinical demand. Thus, treating the disease/disorder symptomatically is the Hobson's choice. The goal of the researchers is to introduce newer therapies in this segment and introducing a new molecule will take long years of development. Hence, drug repurposing/repositioning can be a better substitute in comparison to time consuming and expensive drug discovery and development cycle. Presently, a paradigm shift towards the re-purposing of drugs can be witnessed. Statins which have been previously approved as anti-hyperlipidemic agents are in the limelight of research for re-purposed drugs. Owing to their anti-inflammatory and antioxidant nature, statins act as neuroprotective in several brain disorders. Further they attenuate the amyloid plaques and protein aggregation which are the triggering factors in the Alzheimer's and Parkinson's respectively. In case of Huntington disease and Multiple sclerosis they help in improving the psychomotor symptoms and stimulate remyelination thus acting as neuroprotective. This article reviews the potential of statins in treating neurodegenerative disorders along with a brief discussion on the safety concerns associated with use of statins and human clinical trial data linked with re-tasking statins for neurodegenerative disorders along with the regulatory perspectives involved with the drug repositioning.

PMID:34909647 | PMC:PMC8663947 | DOI:10.1016/j.crphar.2020.100012

Arabian journal of chemistry. 2021 Mar;14(3):102983. doi: 10.1016/j.arabjc.2020.102983. Epub 2021 Jan 10.

ABSTRACT

A novel corona virus SARS-CoV-2 has led to an outbreak of the highly infectious pandemic COVID-19 complicated viral pneumonia. Patients with risk factors frequently develop secondary infections where the role of appropriate antibiotics is mandatory. However, the efforts of drug repurposing lead to recognizing the role of certain antibiotics beyond the management of infection. The current review provided the detailed antiviral, immunomodulatory effect, unique pharmacokinetic profile of two antibiotics namely azithromycin (AZ) and doxycycline (DOX). It summarizes current clinical trials and concerns regarding safety issues of these drugs. Azithromycin (AZ) has amazing lung tissue access, wide range antibacterial efficacy, conceivable antiviral action against COVID-19. It also showed efficacy when combined with other antiviral drugs in limited clinical trials, but many clinicians raise concerns regarding cardiovascular risk in susceptible patients. DOX has a considerable role in the management of pneumonia, it has some advantages including cardiac safety, very good access to lung tissue, potential antiviral, and immunomodulation impact by several mechanisms. The pharmacological profiles of both drugs are heightening considering these medications for further studies in the management of COVID-19.

PMID:34909062 | PMC:PMC7797177 | DOI:10.1016/j.arabjc.2020.102983

Microbiol Spectr. 2021 Dec 15:e0095121. doi: 10.1128/Spectrum.00951-21. Online ahead of print.

ABSTRACT

Staphylococcus aureus is a versatile human commensal bacteria and pathogen that causes various community and hospital-acquired infections. The S. aureus efflux pump NorA which belongs to the major facilitator superfamily, confers resistance to a range of substrates. Many efflux pump inhibitors (EPIs) have been discovered, but none is clinically approved due to their undesirable toxicities. In this study, we have screened clinically approved drugs for possible NorA EPI-like activity. We identified six drugs that showed the best efflux pump inhibition in vitro, with a fractional inhibitory concentration index of ≤0.5, indicating synergism with hydrophilic fluoroquinolones. The mechanistic validation of efflux inhibitory potential was demonstrated in ethidium bromide-based accumulation and efflux inhibition assays. We further confirmed the functionality of EPIs by norfloxacin accumulation assay depicting more realistic proof of the conjecture. None of the EPIs disturbed membrane function or depleted the ATP synthesis levels in bacteria. Both raloxifene and pyrvinium displayed an increase in bactericidal activity of ciprofloxacin in time-kill kinetics, prolonged its post-antibiotic effect, and reduced the frequency of spontaneous resistant mutant development. The combination of EPIs with ciprofloxacin caused significant eradication of preformed biofilms. Moreover, in the murine thigh infection model, a single dose of pyrvinium combined with ciprofloxacin reduced the bacterial burden significantly compared to untreated control and ciprofloxacin alone, indicating the efficacy of the combination. Conclusively, this study represents approved drugs that can be repurposed and combined with antibiotics as NorA EPIs, having anti-biofilm properties to treat severe S. aureus infections at clinically relevant concentrations. IMPORTANCE Staphylococcus aureus is a frequent pathogen bacterium and the predominant cause of worsened nosocomial infections. Efflux pumps contribute to drug efflux and are reportedly associated with biofilm formation, thereby promoting difficult-to-treat biofilm-associated S. aureus infections. One strategy to combat these bacteria is to reduce active efflux and increase pathogen sensitivity to existing antibiotics. Repurposing approved drugs may solve the classical toxicity issues with previous efflux pump inhibitors and help reach sufficient plasma concentrations. We describe the in silico-based screening of FDA-approved drugs that identified six different molecules able to inhibit NorA pump (Major Facilitator Superfamily). Our study highlights that these compounds bind to and block the activity of the NorA pump and increase the sensitivity of S. aureus and methicillin-resistant S. aureus to fluoroquinolones. These drugs combined with fluoroquinolones significantly reduced the preformed biofilms and displayed significant efficacy in the murine thigh infection model when compared to untreated control and ciprofloxacin alone.

PMID:34908453 | DOI:10.1128/Spectrum.00951-21

Sci Rep. 2021 Dec 14;11(1):23933. doi: 10.1038/s41598-021-03418-1.

ABSTRACT

Effective treatment options for head and neck squamous cell carcinoma (HNSCC) are currently lacking. We exploited the drug response and genomic data of the 28 HNSCC cell lines, screened with 4,518 compounds, from the PRISM repurposing dataset to uncover repurposing drug candidates for HNSCC. A total of 886 active compounds, comprising of 418 targeted cancer, 404 non-oncology, and 64 chemotherapy compounds were identified for HNSCC. Top classes of mechanism of action amongst targeted cancer compounds included PI3K/AKT/MTOR, EGFR, and HDAC inhibitors. We have shortlisted 36 compounds with enriched killing activities for repurposing in HNSCC. The integrative analysis confirmed that the average expression of EGFR ligands (AREG, EREG, HBEGF, TGFA, and EPGN) is associated with osimertinib sensitivity. Novel putative biomarkers of response including those involved in immune signalling and cell cycle were found to be associated with sensitivity and resistance to MEK inhibitors respectively. We have also developed an RShiny webpage facilitating interactive visualization to fuel further hypothesis generation for drug repurposing in HNSCC. Our study provides a rich reference database of HNSCC drug sensitivity profiles, affording an opportunity to explore potential biomarkers of response in prioritized drug candidates. Our approach could also reveal insights for drug repurposing in other cancers.

PMID:34907286 | DOI:10.1038/s41598-021-03418-1

Drug Discov Today Technol. 2021 Dec;39:1-12. doi: 10.1016/j.ddtec.2021.06.004. Epub 2021 Jun 24.

ABSTRACT

Standing amidst the COVID-19 pandemic, we have faced major medical and economic crisis in recent times which remains to be an unresolved issue till date. Although the scientific community has made significant progress towards diagnosis and understanding the disease; however, effective therapeutics are still lacking. Several omics-based studies, especially proteomics and interactomics, have contributed significantly in terms of identifying biomarker panels that can potentially be used for the disease prognosis. This has also paved the way to identify the targets for drug repurposing as a therapeutic alternative. US Food and Drug Administration (FDA) has set in motion more than 500 drug development programs on an emergency basis, most of them are focusing on repurposed drugs. Remdesivir is one such success of a robust and quick drug repurposing approach. The advancements in omics-based technologies has allowed to explore altered host proteins, which were earlier restricted to only SARS-CoV-2 protein signatures. In this article, we have reviewed major contributions of proteomics and interactomics techniques towards identifying therapeutic targets for COVID-19. Furthermore, in-silico molecular docking approaches to streamline potential drug candidates are also discussed.

PMID:34906319 | DOI:10.1016/j.ddtec.2021.06.004

PLoS One. 2021 Dec 14;16(12):e0261267. doi: 10.1371/journal.pone.0261267. eCollection 2021.

ABSTRACT

Advances in genome-scale metabolic models (GEMs) and computational drug discovery have caused the identification of drug targets at the system-level and inhibitors to combat bacterial infection and drug resistance. Here we report a structural systems pharmacology framework that integrates the GEM and structure-based virtual screening (SBVS) method to identify drugs effective for Escherichia coli infection. The most complete genome-scale metabolic reconstruction integrated with protein structures (GEM-PRO) of E. coli, iML1515_GP, and FDA-approved drugs have been used. FBA was performed to predict drug targets in silico. The 195 essential genes were predicted in the rich medium. The subsystems in which a significant number of these genes are involved are cofactor, lipopolysaccharide (LPS) biosynthesis that are necessary for cell growth. Therefore, some proteins encoded by these genes are responsible for the biosynthesis and transport of LPS which is the first line of defense against threats. So, these proteins can be potential drug targets. The enzymes with experimental structure and cognate ligands were selected as final drug targets for performing the SBVS method. Finally, we have suggested those drugs that have good interaction with the selected proteins as drug repositioning cases. Also, the suggested molecules could be promising lead compounds. This framework may be helpful to fill the gap between genomics and drug discovery. Results show this framework suggests novel antibacterials that can be subjected to experimental testing soon and it can be suitable for other pathogens.

PMID:34905555 | DOI:10.1371/journal.pone.0261267

Curr Microbiol. 2021 Dec 14;79(1):13. doi: 10.1007/s00284-021-02693-5.

ABSTRACT

Carbapenem-resistant Acinetobacter baumannii has been classified as a top priority for the development of new therapies due to its resistance to most antibiotics. Drug repurposing may be a fast and inexpensive strategy for treating this pathogen. This review aims to critically evaluate repurposed drugs for the treatment of infections caused by carbapenem-resistant A. baumannii, correlating their antimicrobial activity with data available for toxicity and side effects. Some drugs have been suggested as promising candidates for repurposing; however, in some cases, high toxicity and low plasma concentrations reduce applicability in clinical practice. The most favorable applicability is offered by fusidic acid and colistin, possibly combined with a third agent, promising to be well tolerated and achieving satisfactory plasma concentrations.

PMID:34905109 | DOI:10.1007/s00284-021-02693-5

Curr Res Pharmacol Drug Discov. 2021 Dec 4:100072. doi: 10.1016/j.crphar.2021.100072. Online ahead of print.

ABSTRACT

Repurposing regulatory agency approved drugs and investigational compounds with known safety profiles can significantly fast track the drug development timeline over de novo drug discovery, with lower investment requirements and improved attrition rate. These advantages are vital in any epidemic or pandemic situation, where hospital beds are occupied by patients for whom there is no known treatment. Here we examine drug repurposing in the context of human coronaviruses, SARS-CoV, MERS-CoV, and, in particular, SARS-CoV-2, the virus currently causing a continued widespread pandemic with substantial impacts on public health and economy. The key druggable targets explored were those involved in viral entry, viral replication, and viral-induced ARDS, as well as viral proteases, with a focus on the strategy by which the drugs were repurposed.

PMID:34901833 | PMC:PMC8642829 | DOI:10.1016/j.crphar.2021.100072

Adv Ther (Weinh). 2021 Oct;4(10):2100179. doi: 10.1002/adtp.202100179. Epub 2021 Oct 20.

ABSTRACT

[This corrects the article DOI: 10.1002/adtp.202100055.].

PMID:34901385 | PMC:PMC8646851 | DOI:10.1002/adtp.202100179