Union is strength: antiviral and anti-inflammatory drugs for COVID-19.
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ABSTRACT:
SUBMITTER: Naveja JJ
PROVIDER: S-EPMC7590638 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Union is strength: antiviral and anti-inflammatory drugs for COVID-19.
Naveja Jose J JJ Madariaga-Mazón Abraham A Flores-Murrieta Francisco F Granados-Montiel Julio J Maradiaga-Ceceña Marco M Alaniz Víctor Duarte VD Maldonado-Rodriguez Maricruz M García-Morales Jazmín J Senosiain-Peláez Juan Pablo JP Martinez-Mayorga Karina K
Drug discovery today 20201027 1
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Project description:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a wide spectrum of symptom severity, which is manifested at different phases of infection and demands different levels of care. Viral load, host innate-immune response to SARS-CoV-2, and comorbidities have a direct impact on the clinical outcomes of COVID-19 patients and determine the diverse disease trajectories. The initial SARS-CoV-2 penetrance and replication in the host causes death of infected cells, determining the viral response. SARS-CoV-2 replication in the host triggers the activation of host antiviral immune mechanisms, determining the inflammatory response. While a healthy immune response is essential to eliminate infected cells and prevent spread of the virus, a dysfunctional immune response can result in a cytokine storm and hyperinflammation, contributing to disease progression. Current therapies for COVID-19 target the virus and/or the host immune system and may be complicated in their efficacy by comorbidities. Here we review the evidence for use of two classes of anti-inflammatory drugs, glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of COVID-19. We consider the clinical evidence regarding the timing and efficacy of their use, their potential limitations, current recommendations and the prospect of future studies by these and related therapies.
| S-EPMC8280659 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the novel coronavirus disease 2019 (COVID-19), a highly pathogenic and sometimes fatal respiratory disease responsible for the current 2020 global pandemic. Presently, there remains no effective vaccine or efficient treatment strategies against COVID-19. Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines very widely used to alleviate fever, pain, and inflammation (common symptoms of COVID-19 patients) through effectively blocking production of prostaglandins (PGs) via inhibition of cyclooxyganase enzymes. PGs can exert either proinflammatory or anti-inflammatory effects depending on the inflammatory scenario. In this review, we survey the potential roles that NSAIDs and PGs may play during SARS-CoV-2 infection and the development and progression of COVID-19. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.
| S-EPMC7405053 | biostudies-literature
Project description:At the end of 2019, a novel flu-like coronavirus named COVID-19 (coronavirus disease 2019) was recognized by World Health Organization. No specific treatments exist for COVID-19 at this time. New evidence suggests that therapeutic options focusing on antiviral agents may alleviate COVID-19 symptoms as well as those that lead to the decrease in the inflammatory responses. Flavonoids, as phenolic compounds, have attracted considerable attention due to their various biological properties. In this review, the promising effects and possible mechanisms of action of naringenin, a citrus-derived flavonoid, against COVID-19 were discussed. We searched PubMed/Medline, Science direct, Scopus, and Google Scholar databases up to March 2020 using the definitive keywords. The evidence reviewed here indicates that naringenin might exert therapeutic effects against COVID-19 through the inhibition of COVID-19 main protease, 3-chymotrypsin-like protease (3CLpro), and reduction of angiotensin converting enzyme receptors activity. One of the other mechanisms by which naringenin might exert therapeutic effects against COVID-19 is, at least partly, by attenuating inflammatory responses. The antiviral activity of the flavanone naringenin against some viruses has also been reported. On the whole, the favorable effects of naringenin lead to a conclusion that naringenin may be a promising treatment strategy against COVID-19.
| S-EPMC7361426 | biostudies-literature
Project description:The novel coronavirus disease 2019 (COVID-19) pandemic has caused catastrophic damage to human life across the globe along with social and financial hardships. According to the Johns Hopkins University Coronavirus Resource Center, more than 41.3 million people worldwide have been infected, and more than 1,133,000 people have died as of October 22, 2020. At present, there is no available vaccine and a scarcity of efficacious therapies. However, there is tremendous ongoing effort towards identifying effective drugs and developing novel vaccines. Early data from Adaptive COVID-19 Treatment Trials (ACTT) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and compassionate use study have shown promise for remdesivir, leading to emergency authorization by the Food and Drug Administration (FDA) for treatment of hospitalized COVID-19 patients. However, several randomized studies have now shown no benefit or increased adverse events associated with remdesivir treatment. Drug development is a time-intensive process and requires extensive safety and efficacy evaluations. In contrast, drug repurposing is a time-saving and cost-effective drug discovery strategy geared towards using existing drugs instead of de novo drug discovery. Treatments for cancer and COVID-19 often have similar goals of controlling inflammation, inhibiting cell division, and modulating the host microenvironment to control the disease. In this review, we focus on anti-cancer drugs that can potentially be repurposed for COVID-19 and are currently being tested in clinical trials.
| S-EPMC7680713 | biostudies-literature
Project description:Purpose of reviewPatients on disease-modifying anti-rheumatic drugs (DMARDs) remain concerned about potential risks of severe COVID-19 outcomes. Meanwhile, several DMARDs have been proposed as COVID-19 therapies.Recent findingsIn patients with autoimmune diseases, baseline glucocorticoid use is associated with severe COVID-19. While classes of DMARDs (e.g., conventional synthetic, targeted synthetic, and biologic) do not appear to be associated with higher risk, specific medications such as rituximab and sulfasalazine may be associated. Randomized clinical trials (RCTs) show that glucocorticoids reduce mortality in severe COVID-19. RCTs suggest other agents, such as baricitinib, may improve COVID-19 outcomes in certain populations. Baseline glucocorticoid use raises the risk of severe COVID-19 in patients with autoimmune diseases, but glucocorticoids are an effective treatment for those with severe COVID-19. Further research is needed to inform DMARD management in autoimmune disease patients during the pandemic and the role of DMARDs in COVID-19 treatment.
| S-EPMC8065312 | biostudies-literature
Project description:PurposeA number of research articles has been published evaluating safety and efficacy of drugs against COVID-19. This study was undertaken to collate and review the information regarding common proposed anti- viral drugs for easy reference.MethodsThe literature was search was done using terms like severe acute respiratory syndrome or SARS-CoV-2 or 2019-nCoV or SARS-CoV or COVID-19 in combination with drugs or treatment or pharmaco-therapy using PubMed and google scholar to identify relevant articles.ResultsDespite showing good early results, hydroxychloroquine and lopinavir-ritonavir has not shown clinical benefit in randomized controlled trials. However lopinavir in combination with other drugs specially interferon is being investigated. Remdesivir has shown positive effect in terms of clinical improvement and continued to being investigated alone or in combination with other drugs. Favipiravir has shown mixed results and more data from adequately powered study is needed to prove its efficacy.ConclusionsMany drugs which showed positive effect in initial studies could not replicate the same benefit in large randomized controlled trials. There is need to evaluate efficacy and safety of drugs based on high quality evidence before allowing it to be used in general population.
| S-EPMC8291105 | biostudies-literature
Project description:BackgroundWorld Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19).MethodsWe randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry.ResultsAt 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration.ConclusionsThese remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).
| S-EPMC7727327 | biostudies-literature
Project description:Background and purposeSurgical care and pain management for patients with fractures have evolved over the years. We wanted to ascertain if there were any changes in the incidence of non-unions and, if so, whether the use of non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 selective inhibitors, might have an effect.Patients and methodsWe used the National Inpatient Sample (NIS) to estimate the annual number of patients hospitalized for surgical treatment of a non-union between 1993 and 2012, and calculated age-adjusted rates of non-union. We estimated the prevalence of prescriptions for NSAIDs from 1996 through 2012 using the Medical Expenditure Panel Survey (MEPS). The interrupted time-series analysis was used to relate quarterly rates of non-union to changes in prescriptions for NSAIDs between 1996 and 2009.ResultsThe annual estimate of non-unions in the USA declined 30% from 25,634 in 1993 to 17,815 in 2012 (p < 0.001). Specifically, the age-adjusted rate of non-unions decreased by 44% from 8.6 per 10(5) persons in 1996 to 4.8 per 10(5) persons in 2012 (p < 0.001). However, there was an 8% increase in the incidence rate of non-unions (p = 0.003) between 2000 and 2004, when certain COX-2 selective inhibitors were on the market and their prescriptions were prevalent at around 6% among those with fractures. A drop in non-union estimates from 22,321 in 2010 to 18,789 in 2011 (p = 0.04) also coincided with a marked decrease in prescriptions for NSAIDs in patients with fractures, from 22% to 14% (p = 0.02).InterpretationNon-unions in the USA declined substantially between 1993 and 2012, but this was interrupted by changes in prescriptions for NSAIDs, with sustained increases between 2000 and 2004 followed by transient decreases in 2005 and 2011.
| S-EPMC4564789 | biostudies-literature
Project description:AimsMost risks of nonsteroidal anti-inflammatory drugs (NSAIDs) are pharmacological, dose and duration dependent. Usage patterns of prescription-only (POM) or 'over-the-counter (OTC)' NSAIDs may influence risks, but are not commonly described.MethodsThe Echantillon Généraliste de Bénéficiaires database, the permanent 1/97 representative sample from the French national healthcare insurance systems, was queried over 2009-2010 to identify usage patterns, concomitant chronic diseases and cardiovascular medication in OTC and POM NSAID users.ResultsOver 2 years, 229?477 of 526?108 patients had at least one NSAID dispensation; 44?484 patients (19%) were dispensed only OTC NSAIDs (93% ibuprofen) and 121?208 (53%) only POM NSAIDs. The OTC users were younger (39.9 vs. 47.4 years old) and more often female (57 vs. 53%); 69% of OTC users and 49% of POM users had only one dispensation. A mean of 14.6 defined daily doses (DDD) were dispensed over 2 years for OTC?vs. 53 for POM; 93% OTC?vs. 60% POM patients bought ? 30 DDD over 2 years, and 1.5 vs. 12% bought ? 90?DDD. Chronic comorbidities were found in 19% of OTC users vs. 28% of POM users; 24 vs. 37% had at least one dispensation of a cardiovascular drug over the 2 years.ConclusionsMost of the use of NSAIDs appears to be short term, especially for OTC-type NSAIDs, such as ibuprofen. The validity of risk estimates for NSAIDs extrapolated from clinical trials or from observational studies not including OTC-type usage may need to be revised.
| S-EPMC4004409 | biostudies-literature
Project description:The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has posed the world at a pandemic risk. Coronavirus-19 disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which causes pneumonia, requires intensive care unit hospitalization in about 10% of cases and can lead to a fatal outcome. Several efforts are currently made to find a treatment for COVID-19 patients. So far, several anti-viral and immunosuppressive or immunomodulating drugs have demonstrated some efficacy on COVID-19 both in vitro and in animal models as well as in cases series. In COVID-19 patients a pro-inflammatory status with high levels of interleukin (IL)-1B, IL-1 receptor (R)A and tumor necrosis factor (TNF)-? has been demonstrated. Moreover, high levels of IL-6 and TNF-? have been observed in patients requiring intensive-care-unit hospitalization. This provided rationale for the use of anti-rheumatic drugs as potential treatments for this severe viral infection. Other agents, such as hydroxychloroquine and chloroquine might have a direct anti-viral effect. The anti-viral aspect of immunosuppressants towards a variety of viruses has been known since long time and it is herein discussed in the view of searching for a potential treatment for SARS-CoV-2 infection.
| S-EPMC7164894 | biostudies-literature