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Frontiers in Pharmacology 2020The emergence of COVID-19 as a pandemic has resulted in the need for urgent development of vaccines and drugs and the conduction of clinical trials to fight the...
The emergence of COVID-19 as a pandemic has resulted in the need for urgent development of vaccines and drugs and the conduction of clinical trials to fight the outbreak. Because of the time constraints associated with the development of vaccines and effective drugs, drug repurposing and other alternative treatment methods have been used to treat patients that have been infected by the SARS-CoV-2 virus and have acquired COVID-19. The objective of this systematic scoping review is to provide an overview of the molecular mechanism of action of repurposed drugs or alternative treatment medicines used to attenuate COVID-19 disease. The research articles or gray literature, including theses, government reports, and official news online, were identified from four databases and one search engine. The full content of a total of 160 articles that fulfilled our inclusion criteria was analyzed and information about six drugs (ritonavir, lopinavir, oseltamivir, remdesivir, favipiravir, and chloroquine) and four Traditional Chinese Medicines (, TCM combination of and , and ) was extracted. All of the repurposed drugs and complementary medicine that have been used for the treatment of COVID-19 depend on the ability of the drug to inhibit the proliferation of the SARS-CoV-2 virus by binding to enzyme active sites, viral chain termination, or triggering of the molecular pathway, whereas Traditional Chinese Medicine plays a pivotal role in triggering the inflammation pathway, such as the neuraminidase blocker, to fight the SARS-CoV-2 virus.
PubMed: 33746739
DOI: 10.3389/fphar.2020.585331 -
The Medical Journal of Malaysia Nov 2020Currently, there are several attempts to find an effective antiviral drugs against the COVID-19. Although majority of the COVID-19 patients have mild to moderate...
INTRODUCTION
Currently, there are several attempts to find an effective antiviral drugs against the COVID-19. Although majority of the COVID-19 patients have mild to moderate clinical events, up to 5-10% may have severe, life threatening events that urgently require effective drugs. The purpose of this systematic review is to evaluate the effectiveness of antiviral therapies in the treatment of COVID-19.
METHODS
An extensive search was performed in PubMed, EMBASE, Cochrane Library for randomised controlled trials (RCTs), prospective case series studies that evaluated therapies COVID-19. The outcomes searched for were mortality, recovery rate, length of hospital stay and clinical improvement from January to May 15, 2020. Independent reviewers searched, identified, screened, and related studies were included.
RESULTS
Total of five RCTs on 439 patients and seventeen case series involving 1656 patients were found in the specified review period that reported the use of Lopinavir, Ritonavir, Remdesivir. Oseltamivir, Ribavirin in patients with COVID-19; but none of which showed efficacy of antiviral therapy. Such current findings impede researchers from recommending an appropriate and effective antiviral therapy against COVID-19, making it a serious concern for the global community.
DISCUSSION
In the present pandemic and any future epidemics, all the related authorities should pursue many more RCTs, cohort and case series for a prospective outcome in the management and treatment guidelines.
Topics: Antiviral Agents; COVID-19; Humans; Pandemics; Ribavirin; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33219182
DOI: No ID Found -
International Journal of Clinical... Sep 2020Since there is still no definitive conclusion regarding which non-steroidal anti-inflammatory drugs (NSAIDs) are most effective and safe in viral respiratory infections,...
BACKGROUND
Since there is still no definitive conclusion regarding which non-steroidal anti-inflammatory drugs (NSAIDs) are most effective and safe in viral respiratory infections, we decided to evaluate the efficacy and safety of various NSAIDs in viral respiratory infections so that we can reach a conclusion on which NSAID is best choice for coronavirus disease 2019 (COVID-19).
METHODS
A search was performed in Medline (via PubMed), Embase and CENTRAL databases until 23 March 2020. Clinical trials on application of NSAIDs in viral respiratory infections were included.
RESULTS
Six clinical trials were included. No clinical trial has been performed on COVID-19, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome infections. Studies show that ibuprofen and naproxen not only have positive effects in controlling cold symptoms, but also do not cause serious side effects in rhinovirus infections. In addition, it was found that clarithromycin, naproxen and oseltamivir combination leads to decrease in mortality rate and duration of hospitalisation in patients with pneumonia caused by influenza.
CONCLUSION
Although based on existing evidence, NSAIDs have been effective in treating respiratory infections caused by influenza and rhinovirus, since there is no clinical trial on COVID-19 and case-reports and clinical experiences are indicative of elongation of treatment duration and exacerbation of the clinical course of patients with COVID-19, it is recommended to use substitutes such as acetaminophen for controlling fever and inflammation and be cautious about using NSAIDs in management of COVID-19 patients until there are enough evidence. Naproxen may be a good choice for future clinical trials.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Survival Rate; COVID-19 Drug Treatment
PubMed: 32460369
DOI: 10.1111/ijcp.13557 -
Advances in Therapy Jun 2020Influenza in hospitalized intensive care unit (ICU) patients with respiratory failure is associated with 25% mortality, despite timely oseltamivir treatment. A...
INTRODUCTION
Influenza in hospitalized intensive care unit (ICU) patients with respiratory failure is associated with 25% mortality, despite timely oseltamivir treatment. A systematic review of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of alternative neuraminidase inhibitor (NAI) regimens compared to standard of care in patients hospitalized for H1N1, H3N2, or B influenza.
METHODS
The Cochrane collaboration searching methods were followed in Cochrane Library, PubMed, and Web of Science databases (2009-2019). Eligibility criteria were RCTs comparing different regimens of NAIs in hospitalized patients (at least 1 year old) for clinically diagnosed influenza (H1N1, H3N2, or B). Pre-defined endpoints were time to clinical resolution (TTCR), overall mortality, hospital discharge, viral clearance, drug-related adverse events (AEs), and serious adverse events.
RESULTS
Seven trials (1579 patients) were included. Two trials compared two regimens of oral oseltamivir therapy, and one trial compared two regimens of intravenous zanamivir therapy vs oral oseltamivir therapy. Four trials focused on intravenous peramivir therapy: two trials compared two different regimens and two trials compared two different regimens vs oral oseltamivir therapy. Overall, the different regimens were well tolerated, with no significant differences in AEs; nonetheless non-significant differences were reported among different regimens regarding TTCR, mortality, and viral clearance.
CONCLUSION
Higher compared to standard doses of NAIs or systemic peramivir therapy compared to oral oseltamivir therapy did not demonstrate benefit.
Topics: Adult; Antiviral Agents; Clinical Protocols; Critical Care; Humans; Influenza, Human; Neuraminidase; Randomized Controlled Trials as Topic; Respiratory Insufficiency
PubMed: 32347523
DOI: 10.1007/s12325-020-01347-5 -
Terapevticheskii Arkhiv Dec 2020Baloxavir marboxil (baloxavir) is the first cap-dependent endonuclease inhibitor being studied for the treatment of influenza in single oral dosing regimen. This network... (Meta-Analysis)
Meta-Analysis
AIM
Baloxavir marboxil (baloxavir) is the first cap-dependent endonuclease inhibitor being studied for the treatment of influenza in single oral dosing regimen. This network meta-analysis (NMA) evaluated the efficacy and safety of baloxavir compared to other antivirals for influenza in otherwise healthy patients.
METHODS
A systematic literature review was performed on 14 November 2016 in Medline, Embase, CENTRAL, and ICHUSHI to identify randomized controlled trials assessing antivirals for influenza. A NMA including 22 trials was performed to compare the efficacy and safety of baloxavir with other antivirals.
RESULTS
The time to alleviation of all symptoms was significantly shorter for baloxavir compared to zanamivir (difference in median time 19.96 h; 95% CrI [3.23, 39.07]). The time to cessation of viral shedding was significantly shorter for baloxavir than zanamivir and oseltamivir (47.00 h; 95% CrI [28.18, 73.86] and 56.03 h [33.74, 87.86], respectively). The mean decline in virus titer from baseline to 24 h was significantly greater for baloxavir than for the other drugs. Other differences in efficacy outcomes were not significant. No significant differences were found between baloxavir and the other antivirals for safety, except total drug-related adverse events where baloxavir demonstrated a decrease compared to oseltamivir and laninamivir.
CONCLUSION
The NMA suggests that baloxavir demonstrated better or similar efficacy results compared to other antivirals with a comparable safety profile. Baloxavir led to a significant decrease in viral titer versus zanamivir, oseltamivir and peramivir and decreased viral shedding versus zanamivir and oseltamivir.
Topics: Antiviral Agents; Dibenzothiepins; Humans; Influenza, Human; Morpholines; Network Meta-Analysis; Neuraminidase; Pyridones; Triazines
PubMed: 33720617
DOI: 10.26442/00403660.2020.11.000870 -
The American Journal of Chinese Medicine 2018The rapidly changing influenza virus has remained a consistent threat to the well-being of a variety of species on the planet. Influenza virus' high mutation rate has...
The rapidly changing influenza virus has remained a consistent threat to the well-being of a variety of species on the planet. Influenza virus' high mutation rate has allowed the virus to rapidly and continuously evolve, as well as generate new strains that are resistant to the current commercially available antivirals. Thus, the increased resistance has compelled the scientific community to explore alternative compounds that have antiviral effects against influenza virus. In this paper, the authors systematically review numerous herbal extracts that were shown to have antiviral effects against the virus. Specifically, the herbal antiviral targets mainly include hemagglutinin, neuraminidase and matrix 2 proteins. In some instances, herbal extracts inhibited the replication of oseltamivir-resistant strains and certain pentacyclic triterpenes exhibited higher antiviral activity than oseltamivir. This paper also explores the possibility of targeting various host-cell signaling pathways that are utilized by the virus during its replication process. Infected cell pathways are hijacked by intracellular signaling cascades such as NF-kB signaling, PI3K/Akt pathway, MAPK pathway and PKC/PKR signaling cascades. Herbal antivirals have been shown to target these pathways by suppressing nuclear export of influenza vRNP and thus inhibiting the phosphorylation signaling cascade. In conclusion, copious amounts of herbal antivirals have been shown to inhibit influenza virus, however further studies are needed for these new compounds to be up to modern pharmacological standards.
Topics: Antiviral Agents; Depression, Chemical; Drug Resistance, Viral; Drugs, Chinese Herbal; Hemagglutinins; Herbal Medicine; Humans; MAP Kinase Signaling System; NF-kappa B; Neuraminidase; Orthomyxoviridae; Pentacyclic Triterpenes; Phosphorylation; Signal Transduction; Viral Matrix Proteins; Virus Replication
PubMed: 30612461
DOI: 10.1142/S0192415X18500854 -
Expert Review of Clinical Pharmacology Jul 2021Scarce evidence verifying the clinical impact of baloxavir on influenza complications is found. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Scarce evidence verifying the clinical impact of baloxavir on influenza complications is found.
METHODS
PubMed, Cochrane Library, and Web of Science databases were searched through December 2020. Randomized-controlled trials (RCT) that enrolled patients with laboratory-confirmed influenza receiving neuraminidase inhibitors (NAI) or baloxavir comparing to placebo were assessed. PROSPERO Registration-number: CRD42021226854.
RESULTS
Twenty-one RCTs (11,697 patients) were included. Antiviral administration significantly reduced time to clinical resolution (mean difference: -21.3 hours) and total influenza-related complications (OR:0.55, 95%CI: 0.42-0.73). Specifically, antivirals significantly decreased bronchitis (OR:0.54, 95%CI: 0.38-0.75), sinusitis (OR:0.51, 95%CI: 0.33-0.78), acute otitis media (OR:0.48, 95%CI: 0.30-0.77), and antibiotic prescription (OR:0.62; 95%CI: 0.48-0.80). A positive trend favored antivirals administration to reduce pneumonia (OR:0.47, 95%CI: 0.16-1.33), or hospitalization rates (OR:0.65; 95%CI: 0.34-1.24) compared to placebo, but did not reach statistical significance. Adverse events (AE) were reported in 11%, 8.9%, and 5.1% of NAIs, placebo and baloxavir recipients, respectively. Compared with NAIs, administration of baloxavir showed non-significantly reduced AEs (OR:0.74, 95%CI: 0.53-1.04).
CONCLUSIONS
Single-dose baloxavir and NAIs were superior to placebo to reduce complications in uncomplicated influenza, with 40% significant reduction in antibiotic prescription. Safety and efficacy of single-dose baloxavir were non-inferior to NAIs.
Topics: Antiviral Agents; Dibenzothiepins; Enzyme Inhibitors; Humans; Influenza, Human; Morpholines; Neuraminidase; Pyridones; Randomized Controlled Trials as Topic; Triazines
PubMed: 33861168
DOI: 10.1080/17512433.2021.1917378 -
The Journal of International Medical... Jan 2020H7N9 avian influenza virus (AIV) caused human infections in 2013 in China. Phylogenetic analyses indicate that H7N9 AIV is a novel reassortant strain with pandemic...
H7N9 avian influenza virus (AIV) caused human infections in 2013 in China. Phylogenetic analyses indicate that H7N9 AIV is a novel reassortant strain with pandemic potential. We conducted a systemic review regarding virus-induced pathogenesis, vaccine development, and diagnosis of H7N9 AIV infection in humans. We followed PRISMA guidelines and searched PubMed, Web of Science, and Google Scholar to identify relevant articles published between January 2013 and December 2018. Pathogenesis data indicated that H7N9 AIV belongs to low pathogenic avian influenza, which is mostly asymptomatic in avian species; however, H7N9 induces high mortality in humans. Sporadic human infections have recently been reported, caused by highly pathogenic avian influenza viruses detected in poultry. H7N9 AIVs resistant to adamantine and oseltamivir cause severe human infection by rapidly inducing progressive acute community-acquired pneumonia, multiorgan dysfunction, and cytokine dysregulation; however, mechanisms via which the virus induces severe syndromes remain unclear. An H7N9 AIV vaccine is lacking; designs under evaluation include synthesized peptide, baculovirus-insect system, and virus-like particle vaccines. Molecular diagnosis of H7N9 AIVs is suggested over conventional assays, for biosafety reasons. Several advanced or modified diagnostic assays are under investigation and development. We summarized virus-induced pathogenesis, vaccine development, and current diagnostic assays in H7N9 AIVs.
Topics: Animals; Birds; Drug Resistance, Viral; Host-Pathogen Interactions; Humans; Influenza A Virus, H7N9 Subtype; Influenza Vaccines; Influenza in Birds; Influenza, Human
PubMed: 31068040
DOI: 10.1177/0300060519845488 -
Antiviral Therapy 2016Systemic capillary leak syndrome is a rare and potentially lethal disorder characterized by episodes of vascular hyperpermeability, which lead to shock. Although the... (Review)
Review
Systemic capillary leak syndrome is a rare and potentially lethal disorder characterized by episodes of vascular hyperpermeability, which lead to shock. Although the pathogenesis is unknown, some viral infections can act as triggers. We present the first case associated with influenza A virus in adulthood, perform a literature review and discuss its treatment.
Topics: Adult; Antiviral Agents; Capillary Leak Syndrome; Female; Humans; Influenza A virus; Influenza, Human; Oseltamivir
PubMed: 26330157
DOI: 10.3851/IMP2989 -
BMJ (Clinical Research Ed.) Sep 2018
Topics: Female; Humans; Papillomavirus Infections; Papillomavirus Vaccines; Randomized Controlled Trials as Topic; Risk Assessment; Uterine Cervical Neoplasms; Vaccination
PubMed: 30249615
DOI: 10.1136/bmj.k3694