New anti-viral drugs for the treatment of COVID-19 instead of favipiravir.
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ABSTRACT:
SUBMITTER: Aktas A
PROVIDER: S-EPMC7484583 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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
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:Due the current pandemic of COVID-19, an urgent need is required for serious medical treatments of a huge number of patients. The world health organization (WHO) approved Favipiravir (FAV) as a medication for patients infected with corona virus. In the current study, we report the first simple electrochemical, greatly sensitive sensor using MnO2-rGO nanocomposite for the accurate determination of Favipiravir (FAV). The developed sensor showed a high improvement in the electrochemical oxidation of FAV comparing to the unmodified screen-printed electrode (SPE). The suggested platform constituents and the electrochemical measurements parameters were studied. Under optimal experimental parameters, a current response to the concentration change of FAV was found to be in the linear range of 1.0 × 10-8-5.5 × 10-5 M at pH 7.0 with a limit of detection 0.11 µM and a quantification limit of 0.33 µM. The developed platform was confirmed by the precise analysis of FAV in real samples including dosage form and plasma. The developed platform can be applied in different fields of industry quality control and clinical analysis laboratories for the FAV determination.
| S-EPMC8161794 | biostudies-literature
Project description:Background/aimCurrently there is not an effective antiviral treatment for COVID-19, but a large number of drugs have been evaluated since the beginning of the pandemic, and many of them have been used for the treatment of COVID-19 despite the preliminary or conflicting results of the clinical trials. We aimed to review and summarize all of the current knowledge on the antivirals for COVID-19ResultsThere are 2 main drug groups for SARS-CoV-2: agents that target proteins or RNA of the virus or interfere with proteins or biological processes in the host that support the virus. The main drug groups include inhibitors of viral entry into the human cell (convalescent plasma, monoclonal antibodies, nanobodies, mini proteins, human soluble ACE-2, camostat, dutasteride, proxalutamide, bromhexin, hydroxychloroquine, umifenovir nitazoxanid, niclosamide, lactoferrin), inhibitors of viral proteases (lopinavir/ritonavir, PF-07321332, PF-07304814, GC376), inhibitors of viral RNA (remdesivir, favipiravir, molnupiravir, AT-527, merimepodib, PTC299), inhibitors of host proteins supporting virus (plitidepsin, fluvoxamine, ivermectin), and agents supporting host natural immunity
| S-EPMC8771049 | biostudies-literature
Project description:The coronavirus disease-2019 (COVID-19) outbreak all over the world has led the researchers to strive to develop drugs or vaccines to prevent or halt the progression of this ailment. To hasten the treatment process, repurposed drugs are being evaluated. Favipiravir is one such oral drug that was approved for new and reemerging pandemic influenza in Japan in 2014 and has shown potent in vitro activity against severe acute respiratory syndrome coronavirus-2. It has a wide therapeutic safety margin indicated by a wide CC50/EC50 ratio for a high dose. From the clinical studies in COVID-19, it has shown rapid viral clearance as compared to lopinavir/ritonavir (LPV/RTV) and superior recovery rate than umifenovir. Overall, favipiravir has shown promising results in clinical studies in China, Russia, and Japan, and more trials are underway in multiple countries, including USA, UK, and India. Recently, treatment guidelines from many countries and some states from India have included favipiravir in the treatment protocol. This review provides insights into the evidence-based evolving role of favipiravir in the management of COVID-19 infection with emphasis on benefits of initiating an early antiviral therapy with special focus on favipiravir, its pharmacodynamic, pharmacokinetic, in vitro, clinical data, and inclusion in the treatment protocols of COVID-19.
| S-EPMC7831863 | biostudies-literature
Project description:With over 16 million cases reported from across the globe, the SARS-CoV-2, a mere 125 microns in diameter, has left an indelible impact on our world. With the paucity of new drugs to combat this disease, the medical community is in a race to identify repurposed drugs that may be effective against this novel coronavirus. One of the drugs which has recently garnered much attention, especially in India, is an anti-viral drug originally designed for influenza, called favipiravir. In this article, we have tried to provide a comprehensive, evidence-based review of this drug in the context of the present pandemic to elucidate its role in the management of COVID-19.
| S-EPMC7467067 | biostudies-literature
Project description:We developed three different protein arrays to measure IgG autoantibodies associated with Connective Tissue Diseases (CTDs), Anti-Cytokine Antibodies (ACA), and anti-viral antibody responses in 147 hospitalized COVID-19 patients in three different centers.
2021-07-24 | GSE180742 | GEO
Project description: Not available
| S-EPMC7167223 | biostudies-literature
Project description:BackgroundThe coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the health workforce and societies worldwide. Favipiravir was suggested by some experts to be effective and safe to use in COVID-19. Although this drug has been evaluated in randomized controlled trials (RCTs), it is still unclear if it has a definite role in the treatment of COVID-19.ObjectivesTo assess the effects of favipiravir compared to no treatment, supportive treatment, or other experimental antiviral treatment in people with acute COVID-19.Search methodsWe searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, and three other databases, up to 18 July 2023.Selection criteriaWe searched for RCTs evaluating the efficacy of favipiravir in treating people with COVID-19.Data collection and analysisWe used standard Cochrane methodological procedures for data collection and analysis. We used the GRADE approach to assess the certainty of evidence for each outcome.Main resultsWe included 25 trials that randomized 5750 adults (most under 60 years of age). The trials were conducted in Bahrain, Brazil, China, India, Iran, Kuwait, Malaysia, Mexico, Russia, Saudi Arabia, Thailand, the UK, and the USA. Most participants were hospitalized with mild to moderate disease (89%). Twenty-two of the 25 trials investigated the role of favipiravir compared to placebo or standard of care, whilst lopinavir/ritonavir was the comparator in two trials, and umifenovir in one trial. Most trials (24 of 25) initiated favipiravir at 1600 mg or 1800 mg twice daily for the first day, followed by 600 mg to 800 mg twice a day. The duration of treatment varied from five to 14 days. We do not know whether favipiravir reduces all-cause mortality at 28 to 30 days, or in-hospital (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.49 to 1.46; 11 trials, 3459 participants; very low-certainty evidence). We do not know if favipiravir reduces the progression to invasive mechanical ventilation (RR 0.86, 95% CI 0.68 to 1.09; 8 trials, 1383 participants; very low-certainty evidence). Favipiravir may make little to no difference in the need for admission to hospital (if ambulatory) (RR 1.04, 95% CI 0.44 to 2.46; 4 trials, 670 participants; low-certainty evidence). We do not know if favipiravir reduces the time to clinical improvement (defined as time to a 2-point reduction in patients' admission status on the WHO's ordinal scale) (hazard ratio (HR) 1.13, 95% CI 0.69 to 1.83; 4 trials, 721 participants; very low-certainty evidence). Favipiravir may make little to no difference to the progression to oxygen therapy (RR 1.20, 95% CI 0.83 to 1.75; 2 trials, 543 participants; low-certainty evidence). Favipiravir may lead to an overall increased incidence of adverse events (RR 1.27, 95% CI 1.05 to 1.54; 18 trials, 4699 participants; low-certainty evidence), but may result in little to no difference inserious adverse eventsattributable to the drug (RR 1.04, 95% CI 0.76 to 1.42; 12 trials, 3317 participants; low-certainty evidence).Authors' conclusionsThe low- to very low-certainty evidence means that we do not know whether favipiravir is efficacious in people with COVID-19 illness, irrespective of severity or admission status. Treatment with favipiravir may result in an overall increase in the incidence of adverse events but may not result in serious adverse events.
| S-EPMC10840071 | biostudies-literature
Project description:The year 2020 witnessed a heavy death toll due to COVID-19, calling for a global emergency. The continuous ongoing research and clinical trials paved the way for vaccines. But, the vaccine efficacy in the long run is still questionable due to the mutating coronavirus, which makes drug re-positioning a reasonable alternative. COVID-19 has hence fast-paced drug re-positioning for the treatment of COVID-19 and its symptoms. This work builds computational models using matrix completion techniques to predict drug-virus association for drug re-positioning. The aim is to assist clinicians with a tool for selecting prospective antiviral treatments. Since the virus is known to mutate fast, the tool is likely to help clinicians in selecting the right set of antivirals for the mutated isolate. The main contribution of this work is a manually curated database publicly shared, comprising of existing associations between viruses and their corresponding antivirals. The database gathers similarity information using the chemical structure of drugs and the genomic structure of viruses. Along with this database, we make available a set of state-of-the-art computational drug re-positioning tools based on matrix completion. The tools are first analysed on a standard set of experimental protocols for drug target interactions. The best performing ones are applied for the task of re-positioning antivirals for COVID-19. These tools select six drugs out of which four are currently under various stages of trial, namely Remdesivir (as a cure), Ribavarin (in combination with others for cure), Umifenovir (as a prophylactic and cure) and Sofosbuvir (as a cure). Another unanimous prediction is Tenofovir alafenamide, which is a novel Tenofovir prodrug developed in order to improve renal safety when compared to its original counterpart (older version) Tenofovir disoproxil. Both are under trail, the former as a cure and the latter as a prophylactic. These results establish that the computational methods are in sync with the state-of-practice. We also demonstrate how the drugs to be used against the virus would vary as SARS-Cov-2 mutates over time by predicting the drugs for the mutated strains, suggesting the importance of such a tool in drug prediction. We believe this work would open up possibilities for applying machine learning models to clinical research for drug-virus association prediction and other similar biological problems.
| S-EPMC8079380 | biostudies-literature