scholarly journals An Update on Antiviral Therapy Against SARS-CoV-2: How Far Have We Come?

2021 ◽  
Vol 12 ◽  
Author(s):  
Omkar Indari ◽  
Shweta Jakhmola ◽  
Elangovan Manivannan ◽  
Hem Chandra Jha
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Drug Repurposing ◽  
Clinical Findings ◽  
Open Label ◽  
Plasma Therapy ◽  
Clinical Safety ◽  
Treatment Research ◽  
Repurposed Drugs ◽  
Approved Drugs

COVID-19 pandemic has spread worldwide at an exponential rate affecting millions of people instantaneously. Currently, various drugs are under investigation to treat an enormously increasing number of COVID-19 patients. This dreadful situation clearly demands an efficient strategy to quickly identify drugs for the successful treatment of COVID-19. Hence, drug repurposing is an effective approach for the rapid discovery of frontline arsenals to fight against COVID-19. Successful application of this approach has resulted in the repurposing of some clinically approved drugs as potential anti-SARS-CoV-2 candidates. Several of these drugs are either antimalarials, antivirals, antibiotics or corticosteroids and they have been repurposed based on their potential to negate virus or reduce lung inflammation. Large numbers of clinical trials have been registered to evaluate the effectiveness and clinical safety of these drugs. Till date, a few clinical studies are complete and the results are primary. WHO also conducted an international, multi-country, open-label, randomized trials-a solidarity trial for four antiviral drugs. However, solidarity trials have few limitations like no placebos were used, additionally any drug may show effectiveness for a particular population in a region which may get neglected in solidarity trial analysis. The ongoing randomized clinical trials can provide reliable long-term follow-up results that will establish both clinical safety and clinical efficacy of these drugs with respect to different regions, populations and may aid up to worldwide COVID-19 treatment research. This review presents a comprehensive update on majorly repurposed drugs namely chloroquine, hydroxychloroquine, remdesivir, lopinavir-ritonavir, favipiravir, ribavirin, azithromycin, umifenovir, oseltamivir as well as convalescent plasma therapy used against SARS-CoV-2. The review also summarizes the data recorded on the mechanism of anti-SARS-CoV-2 activity of these repurposed drugs along with the preclinical and clinical findings, therapeutic regimens, pharmacokinetics, and drug-drug interactions.

scholarly journals Repurposing of Antimicrobial Agents for Cancer Therapy: What Do We Know?

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3193
Author(s):  
Christina Pfab ◽  
Luisa Schnobrich ◽  
Samir Eldnasoury ◽  
André Gessner ◽  
Nahed El-Najjar
Keyword(s):  
Clinical Trials ◽  
Antimicrobial Agents ◽  
Large Body ◽  
Drug Repurposing ◽  
Extensive Discussion ◽  
Attrition Rates ◽  
Beneficial Effects ◽  
Stage Of Development ◽  
Development Costs ◽  
Approved Drugs

The substantial costs of clinical trials, the lengthy timelines of new drug discovery and development, along the high attrition rates underscore the need for alternative strategies for finding quickly suitable therapeutics agents. Given that most approved drugs possess more than one target tightly linked to other diseases, it encourages promptly testing these drugs in patients. Over the past decades, this has led to considerable attention for drug repurposing, which relies on identifying new uses for approved or investigational drugs outside the scope of the original medical indication. The known safety of approved drugs minimizes the possibility of failure for adverse toxicology, making them attractive de-risked compounds for new applications with potentially lower overall development costs and shorter development timelines. This latter case is an exciting opportunity, specifically in oncology, due to increased resistance towards the current therapies. Indeed, a large body of evidence shows that a wealth of non-cancer drugs has beneficial effects against cancer. Interestingly, 335 drugs are currently being evaluated in different clinical trials for their potential activities against various cancers (Redo database). This review aims to provide an extensive discussion about the anti-cancer activities exerted by antimicrobial agents and presents information about their mechanism(s) of action and stage of development/evaluation.

scholarly journals A Scoping Insight on Potential Prophylactics, Vaccines and Therapeutic Weaponry for the Ongoing Novel Coronavirus (COVID-19) Pandemic- A Comprehensive Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Priyanka Dash ◽  
Subhashree Mohapatra ◽  
Sayantan Ghosh ◽  
Bismita Nayak
Keyword(s):  
Clinical Trials ◽  
Therapeutic Strategy ◽  
Antiviral Agents ◽  
Fast Response ◽  
Etiologic Agent ◽  
Prolonged Treatment ◽  
Rdrp Activity ◽  
Open Label ◽  
Plasma Therapy ◽  
Mesenchymal Stem Cell Therapy

The emergence of highly virulent CoVs (SARS-CoV-2), the etiologic agent of novel ongoing “COVID-19” pandemics has been marked as an alarming case of pneumonia posing a large global healthcare crisis of unprecedented magnitude. Currently, the COVID-19 outbreak has fueled an international demand in the biomedical field for the mitigation of the fast-spreading illness, all through the urgent deployment of safe, effective, and rational therapeutic strategies along with epidemiological control. Confronted with such contagious respiratory distress, the global population has taken significant steps towards a more robust strategy of containment and quarantine to halt the total number of positive cases but such a strategy can only delay the spread. A substantial number of potential vaccine candidates are undergoing multiple clinical trials to combat COVID-19 disease, includes live-attenuated, inactivated, viral-vectored based, sub-unit vaccines, DNA, mRNA, peptide, adjuvant, plant, and nanoparticle-based vaccines. However, there are no licensed anti-COVID-19 drugs/therapies or vaccines that have proven to work as more effective therapeutic candidates in open-label clinical trial studies. To counteract the infection (SARS-CoV-2), many people are under prolonged treatment of many chemical drugs that inhibit the PLpro activity (Ribavirin), viral proteases (Lopinavir/Ritonavir), RdRp activity (Favipiravir, Remdesivir), viral membrane fusion (Umifenovir, Chloroquine phosphate (CQ), Hydroxychloroquine phosphate (HCQ), IL-6 overexpression (Tocilizumab, Siltuximab, Sarilumab). Mesenchymal Stem Cell therapy and Convalescent Plasma Therapy have emerged as a promising therapeutic strategy against SARS-CoV-2 virion. On the other hand, repurposing previously designed antiviral agents with tolerable safety profile and efficacy could be the only promising approach and fast response to the novel virion. In addition, research institutions and corporations have commenced the redesign of the available therapeutic strategy to manage the global crisis. Herein, we present succinct information on selected anti-COVID-19 therapeutic medications repurposed to combat SARS-CoV-2 infection. Finally, this review will provide exhaustive detail on recent prophylactic strategies and ongoing clinical trials to curb this deadly pandemic, outlining the major therapeutic areas for researchers to step in.

Randomized Clinical Trials in Pediatric Dentistry: Application of Evidence-Based Dentistry through the CONSORT Statement

2019 ◽  
Vol 43 (4) ◽  
pp. 219-230 ◽  
Author(s):  
Arturo Garrocho-Rangel ◽  
Socorro Ruiz-Rodríguez ◽  
César Gaitán-Fonseca ◽  
Amaury Pozos-Guillén
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Internal Validity ◽  
Consort Statement ◽  
Pediatric Dentistry ◽  
Clinical Findings ◽  
Evidence Based ◽  
The Consort Statement ◽  
Pediatric Dentists ◽  
Evidence Based Dentistry

In order to include appropriate informed decisions on dental therapeutic or preventive procedures in children, Pediatric Dentists should apply the fundamentals of “Evidence-Based Dentistry” (EBD). This oral health approach assists clinicians in understanding and applying the most relevant research published on evidence in the clinical setting when treating their patients. One of the crucial steps of EBD is to critically appraise and use the primary articles about therapy or prevention, namely, Randomized Clinical Trials (RCT), the study design that best addresses the questions related with these clinical areas. The aim of the present paper was to provide the basic concepts and an example of how to critically read and understand articles on RCT studies in Pediatric Dentistry employing the CONSORT statement, a process that involves assessing the reliability of results, risk of bias (internal validity), and applicability of reported clinical findings (external validity).

scholarly journals Topical Corticosteroids a Viable Solution for Oral Graft versus Host Disease? A Systematic Insight on Randomized Clinical Trials

Medicina ◽  
2020 ◽  
Vol 56 (7) ◽  
pp. 349
Author(s):  
Arin Sava ◽  
Andra Piciu ◽  
Sergiu Pasca ◽  
Alexandru Mester ◽  
Ciprian Tomuleasa
Keyword(s):  
Clinical Trials ◽  
Graft Versus Host Disease ◽  
Randomized Clinical Trials ◽  
Open Label ◽  
Double Blind ◽  
Host Disease ◽  
Graft Versus Host ◽  
Overall Response ◽  
Topical Corticosteroids ◽  
Oral Gvhd

Background and Objectives: This research attempts to provide a clear view of the literature on randomized clinical trials (RCTs) concerning the efficacy of topical dexamethasone, clobetasol and budesonide in oral graft versus host disease (GVHD). Materials and Methods: An electronic search of the PubMed, Web of Science and Scopus databases was carried out for eligible RCTs. Studies were included if they had adult patients with oral GVHD treatment with topical corticosteroids, and if the RCT study was published in English. The Cochrane Risk of Bias tool was used to assess the quality of these studies. Overall, three RCTs were included (an Open, Randomized, Multicenter Trial; a Randomized Double-Blind Clinical Trial; and an Open-Label Phase II Randomized Trial). Results: The trials involved 76 patients, of which 44 patients received topical dexamethasone, 14 patients received topical clobetasol and 18 patients received topical budesonide. Topical agents were most frequently used when oral tissues were the sole site of involvement. It appears that the best overall response is present for budesonide with no difference between the four arms, followed by clobetasol, and then by dexamethasone. The limitation of the current study is mainly represented by the fact that overall response was derived in two of the studies from other parameters. Moreover, both budesonide and clobetasol were used in only one study each, while two assessed dexamethasone. Conclusions: Based on the clinical trials, all three agents seem to be effective in treating oral GVHD and had a satisfactory safety profile. There is still a need for assessing high quality RCTs to assess the efficacy of these therapies on a larger cohort.

scholarly journals An overview of treatment options for COVID-19

2020 ◽  
Vol 9 (11) ◽  
pp. 1770
Author(s):  
Madhusmita Mohanty Mohapatra ◽  
Manju Rajaram ◽  
Dharm Prakash Dwivedi ◽  
Vishnukant Govindraj ◽  
Pratap Upadhya
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Unknown Origin ◽  
The Novel ◽  
Clinical Trial Registry ◽  
Repurposed Drugs ◽  
Novel Coronavirus ◽  
Meta Analyses ◽  
Effective Drugs

Severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2) which emerged in Wuhan initially as pneumonia of unknown origin in December 2019, later spread to whole world and became pandemic on 11th March, 2020. Many drugs have been proposed but are backed without clinical evidence. Scientific bodies are in the row to discover a reliable vaccine and effective drugs against the novel coronavirus. Many antiviral and anti-parasitic drugs which were thought to have some effect on Coronavirus disease 2019 (COVID-19) have been tried during the crisis but none have shown concrete evidence of action. Randomized clinical trials on the repurposed drugs are now registered under clinical trial registry to look at the safety profile and efficacy of the drugs to be used against SARS-CoV-2. Many meta-analyses are being conducted worldwide to frame evidence for the fight against this novel coronavirus. We are providing below a review of various drugs that have been tried for treatment of COVID-19 as well as different clinical trials which are underway.

scholarly journals Repurposing Immunomodulatory Therapies against Coronavirus Disease 2019 (COVID-19) in the Era of Cardiac Vigilance: A Systematic Review

2020 ◽  
Vol 9 (9) ◽  
pp. 2935
Author(s):  
Courtney M. Campbell ◽  
Avirup Guha ◽  
Tamanna Haque ◽  
Tomas G. Neilan ◽  
Daniel Addison
Keyword(s):  
Clinical Trials ◽  
Cancer Therapies ◽  
Clinical Safety ◽  
Randomized Evaluation ◽  
Therapeutic Trials ◽  
Inflammatory Phase ◽  
Repurposed Drugs ◽  
Intervention Trials ◽  
Investigational Agents ◽  
Immunomodulatory Therapies

The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in efforts to identify therapies to ameliorate adverse clinical outcomes. The recognition of the key role for increased inflammation in COVID-19 has led to a proliferation of clinical trials targeting inflammation. The purpose of this review is to characterize the current state of immunotherapy trials in COVID-19, and focuses on associated cardiotoxicities, given the importance of pharmacovigilance. The search terms related to COVID-19 were queried in ClinicalTrials.gov. A total of 1621 trials were identified and screened for interventional trials directed at inflammation. Trials (n = 226) were fully assessed for the use of a repurposed drug, identifying a total of 141 therapeutic trials using a repurposed drug to target inflammation in COVID-19 infection. Building on the results of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial demonstrating the benefit of low dose dexamethasone in COVID-19, repurposed drugs targeting inflammation are promising. Repurposed drugs directed at inflammation in COVID-19 primarily have been drawn from cancer therapies and immunomodulatory therapies, specifically targeted anti-inflammatory, anti-complement, and anti-rejection agents. The proposed mechanisms for many cytokine-directed and anti-rejection drugs are focused on evidence of efficacy in cytokine release syndromes in humans or animal models. Anti-complement-based therapies have the potential to decrease both inflammation and microvascular thrombosis. Cancer therapies are hypothesized to decrease vascular permeability and inflammation. Few publications to date describe using these drugs in COVID-19. Early COVID-19 intervention trials have re-emphasized the subtle, but important cardiotoxic sequelae of potential therapies on outcomes. The volume of trials targeting the COVID-19 hyper-inflammatory phase continues to grow rapidly with the evaluation of repurposed drugs and late-stage investigational agents. Leveraging known clinical safety profiles and pharmacodynamics allows swift investigation in clinical trials for a novel indication. Physicians should remain vigilant for cardiotoxicity, often not fully appreciated in small trials or in short time frames.

scholarly journals Identification of SARS-CoV-2–induced pathways reveals drug repurposing strategies

2021 ◽  
Vol 7 (27) ◽  
pp. eabh3032
Author(s):  
Namshik Han ◽  
Woochang Hwang ◽  
Konstantinos Tzelepis ◽  
Patrick Schmerer ◽  
Eliza Yankova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Viral Replication ◽  
Rapid Development ◽  
Drug Repurposing ◽  
Mechanisms Of Action ◽  
Neural Network Analysis ◽  
Cell Assays ◽  
Artificial Neural Network Analysis ◽  
Approved Drugs ◽  
Disease Signatures

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates the rapid development of new therapies against coronavirus disease 2019 (COVID-19) infection. Here, we present the identification of 200 approved drugs, appropriate for repurposing against COVID-19. We constructed a SARS-CoV-2–induced protein network, based on disease signatures defined by COVID-19 multiomics datasets, and cross-examined these pathways against approved drugs. This analysis identified 200 drugs predicted to target SARS-CoV-2–induced pathways, 40 of which are already in COVID-19 clinical trials, testifying to the validity of the approach. Using artificial neural network analysis, we classified these 200 drugs into nine distinct pathways, within two overarching mechanisms of action (MoAs): viral replication (126) and immune response (74). Two drugs (proguanil and sulfasalazine) implicated in viral replication were shown to inhibit replication in cell assays. This unbiased and validated analysis opens new avenues for the rapid repurposing of approved drugs into clinical trials.

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