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1.
EClinicalMedicine ; 49: 101484, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1881934

ABSTRACT

Background: The effectiveness of combination therapy for COVID-19 pneumonia remains unclear. We evaluated favipiravir, camostat, and ciclesonide combination therapy in patients with moderate COVID-19 pneumonia. Methods: In this open-label phase 3 study, hospitalized adults who were positive for SARS-CoV-2 and had COVID-19 pneumonia were enrolled prior to official vaccination drive in Japan. Participants were randomly assigned to favipiravir monotherapy or favipiravir + camostat + ciclesonide combination therapy. The primary outcome was the length of hospitalization due to COVID-19 infection after study treatment. The hospitalization period was calculated from the time of admission to the time of patient discharge using the clinical management guide of COVID-19 for front-line healthcare workers developed by the Japanese Ministry of Health, Labour, and Welfare (Version 3). Cases were registered between November 11, 2020, and May 31, 2021. Japan Registry of Clinical Trials registration: jRCTs031200196. Findings: Of 121 enrolled patients, 56 received monotherapy and 61 received combination therapy. Baseline characteristics were balanced between the groups. The median time of hospitalization was 10 days for the combination and 11 days for the monotherapy group. The median time to discharge was statistically significantly lower in the combination therapy vs monotherapy group (HR, 1·67 (95% CI 1·03-2·7; P = 0·035). The hospital discharge rate was statistically significantly higher in the combination therapy vs monotherapy group in patients with less severe COVID-19 infections and those who were ≤60 years. There were no significant differences in clinical findings between the groups at 4, 8, 11, 15, and 29 days. Adverse events were comparable between the groups. There were two deaths, with one in each group. Interpretation: Combination oral favipiravir, camostat and, ciclesonide therapy could decrease the length of hospitalization stays without safety concerns in patients with moderate COVID-19 pneumonia. However, lack of hard clinical primary outcome is one of the major limitations of the study. Funding: This research was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 20fk0108261h0001.

2.
Chem Zvesti ; : 1-17, 2021 May 16.
Article in English | MEDLINE | ID: covidwho-1877948

ABSTRACT

ABSTRACT: Specific inhibition of the viral RNA-dependent RNA polymerase (RdRp) of the newly-emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising strategy for developing highly potent medicines for coronavirus disease 2019 (COVID-19). However, almost all of the reported viral RdRp inhibitors (either repurposed drugs or new antiviral agents) lack selectivity against the SARS-CoV-2 RdRp. Herein, I discovered a new favipiravir derivative, (E)-N-(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20), as the first potent SARS-CoV-2 inhibitor with very high selectivity (209- and 45-fold more potent than favipiravir and remdesivir, respectively). Based on the significant reduction in the in vitro SARS-CoV-2 replication/copies, strong computational cyanorona-20 ligand-RdRp protein interactions, and anti-RdRp activity of the parent favipiravir drug, SARS-CoV-2 inhibition is thought to be mediated through the coronaviral-2 RdRp inhibition. This promising selective anti-COVID-19 compound is also, to the best of our knowledge, the first bioactive derivative of favipiravir, the known antiinfluenza and antiviral drug. This new nucleoside analog was designed, synthesized, characterized, computationally studied (through pharmacokinetic calculations along with computational molecular modeling and prediction), and biologically evaluated for its anti-COVID-19 activities (through a validated in vitro anti-COVID-19 assay). The results of the biological assay showed that cyanorona-20 surprisingly exhibited very significant anti-COVID-19 activity (anti-SARS-CoV-2 EC50 = 0.45 µM), and, in addition, it could be also a very promising lead compound for the design of new anti-COVID-19 agents. Cyanorona-20 is a new favipiravir derivative with promise for the treatment of SARS-CoV-2 infection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11696-021-01640-9.

3.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-337959

ABSTRACT

Background: Well tolerated antivirals administered early in the course of COVID-19 infection when the viremia is highest could prevent progression to severe disease. Favipiravir inhibits SARS-CoV-2 viral replication in vitro with evidence of clinical benefit in open label trials. Placebo controlled studies of people with early symptomatic COVID-19 with regular assessments of SARS-CoV-2 viral load can determine if it has an antiviral effect and improves clinical outcomes. Methods: People with PCR-confirmed COVID-19 and 5 days or less of symptoms were randomised 1:1 to favipiravir 1800 mg on day 1, then 800 mg twice daily or matched placebo for 14 days. SARS-CoV-2 viral load was quantitated from second daily self-collected nose-throat swabs while receiving study drug. The primary endpoint was time to virological cure defined as 2 successive swabs negative for SARS-CoV-2 by PCR and secondary outcomes were progression of disease severity, symptom resolution and safety. Findings: Between 31 July 2020 and 19 September 2021, 200 people were enrolled (199 in the community, 1 in hospital) with 190 receiving one or more doses of drug (modified intention to treat [mITT] population). There was no difference in time to virological cure (Log-rank p=0.6 comparing Kaplan Meier curves), progression to hospitalisation (14 favipiravir, 9 placebo;p=0.38), time to symptom resolution (cough, fever, sore throat) and there were no deaths. 51 people related an adverse event that was possibly drug related, but these were evenly distributed (n=24 favipiravir, n=27 placebo). Sensitivity analyses where the definition of virological cure was changed to: a single negative PCR, exclude datapoints based on the presence or absence of human DNA in the swab, a SARS-CoV-2 viral load < 300 copies/mL being considered negative all demonstrated no difference between arms. Interpretation: Favipiravir does not improve the time to virological cure or clinical outcomes and shows no evidence of an antiviral effect when treating early symptomatic COVID-19 infection. Trial Registration Details: This trial was registered under (NCT04445467). Funding Information: The study was supported in part by grants from the Commonwealth Bank and the Lord Mayor’s Charitable Foundation. JHM is supported by the Medical Research Future Fund, AYP, JT are supported by the Australian National Health and Medical Research Council. Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the Alfred Ethics Committee (No 406/20) and all participants provided informed consent.

4.
Eurasian Chemical Communications ; 4(9):835-851, 2022.
Article in English | Scopus | ID: covidwho-1876372

ABSTRACT

This study included the preparation and identification of copper oxide nanoparticles (CuNPs) prepared from eucalyptus leaf extract using modern and advanced detection and analysis devices: XRD, AFM, SEM, UV-Vis, and TEM. The results of the tests indicated that the prepared particles are spherical and rod-shaped, with average diameters ranging from 32.55-37.94 nm, and the results showed that the copper oxide nanoparticles were within the nano-scale, and the wavelength of the drug is (322) nanometers. The factors affecting the loading of the drug (Favipiravir) at a concentration of (40 µg/mL) on the surface of activated charcoal prepared from eucalyptus leaves were studied, as well with a weight of 0.1 g and in the presence of copper oxide nanoparticles with different concentrations. It was found that the equilibrium time is 25 minutes, and the thermodynamic functions were calculated at different temperatures. The results illustrated that the loading process by using exothermic adsorption (physical adsorption), is less random process and spontaneously. The possibility of using the loaded substance (Favipiravir:CuNPs) to inhibit microorganisms such as viruses, bacteria, and fungi was studied, and by the presence of the surface active substance sodium dodecyl sulphate SDS, it was found that it has the ability to inhibit by 100%, as a result of the merging of the tail of the superficial active substances with the fatty membrane of the virus, the other microorganisms, its dismantling, and encapsulation of its parts. The vaccines and therapeutic drugs developed on the basis of nano-medicine, which are currently undergoing clinical trials, have the potential to become innovative alternatives to defeat COVID-19 in the future. Copyright © 2022 by SPC (Sami Publishing Company).

5.
Adverse Drug Reactions Journal ; 24(4):169-174, 2022.
Article in Chinese | Scopus | ID: covidwho-1875842

ABSTRACT

Objective To explore the occurrence and influencing factors of serum uric acid elevation in patients with coronavirus disease 2019 (COVID⁃19) treated with favipiravir. Methods Medical records of patients with COVID⁃19 who were hospitalized in Beijing Ditan Hospital between June 1, 2020 and June 30, 2021 and treated with the 5- or 10-day regimen of favipiravir were collected and retrospectively analyzed. After favipiravir withdrawal, if the elevation in serum uric acid was ≥30% of baseline level, it was defined as serum uric acid elevation. Then patients were divided into serum uric acid elevation group and non-serum uric acid elevation group. The clinical characteristics such as gender, age, body mass index, comorbidities, smoking and drinking behavior, COVID⁃19 grade, favipiravir regimen, and serum uric acid level and renal function before treatment in patients between the 2 groups were compared. Influencing factors of favipiravir⁃associated serum uric acid elevation was analyzed using multivariate logistic regression method. Results A total of 179 patients were included in the analysis, including 104 (58.1%) males and 75 (41.9%) females, aged from 19 to 70 years with a median age of 43 years. The level of serum uric acid in 179 patients after favipiravir treatment was significantly higher than before [(451±119) μmol/L vs. (332±94) μmol/L, P<0.001]. The change rate of serum uric acid from baseline level ranged from -57.1% to 157.8% with the median of 38.6%. The elevation in serum uric acid of ≥ 30% of baseline level occurred in 108 (60.3%) patients. The incidences of serum uric acid elevation in patients treated with 5-day and 10-day regi⁃ mens of favipiravir were 46.8% (36/77) and 70.6% (72/102), respectively, and the difference between them was significant (P=0.001). Multivariate logistic regression analysis showed that body mass index 24.0 to <28.0 kg/m2 (OR=3.109, 95%CI: 1.209-7.994, P=0.019) and 10-day regimen of favipiravir (OR=3.017, 95%CI: 1.526-5.964, P=0.001) were independent risk factors for favipiravir⁃associated serum uric acid elevation. Conclusions More than half of COVID⁃19 patients treated with favipiravir can develop serum uric acid elevation. Overweight and 10-day regimen of favipiravir are independent risk factors for serum uric acid elevation in patients. © 2022 Adverse Drug Reactions Journal.

6.
Arch Gynecol Obstet ; 2022 May 27.
Article in English | MEDLINE | ID: covidwho-1872414

ABSTRACT

PURPOSE: As in vitro and in vivo studies reported antiviral efficacy against RNA viruses, favipiravir, a pyrazinecarboxamide derivative, has become one of the treatment options for COVID-19 in some countries including Turkey. Preclinical studies demonstrated the risk for teratogenicity and embryotoxicity. Hence, the drug is contraindicated during pregnancy. Although limited in numbers, case-based evaluations indicate that favipiravir might not be a major teratogen in human pregnancies. This study aimed to present and analyze the outcomes of favipiravir exposure during pregnancy. METHODS: In this case series, the outcomes of nine pregnancies that were referred to the Teratology Information Service of Dokuz Eylul University Faculty of Medicine, Department of Medical Pharmacology between 01 April 2020 and 30 November 2021 were retrospectively evaluated. RESULTS: One spontaneous abortion, two elective terminations, one preterm live delivery and five term live deliveries were detected. The premature newborn was reported dead on the 5th day of neonatal intensive care unit admission. Physiological jaundice and transient respiratory distress were recorded in two term infants. One term infant was antenatally diagnosed with renal pelviectasis, but the findings resolved postnatally without requiring intervention. CONCLUSION: The data indicate that favipiravir is not likely to be a major teratogen. Yet, it is not possible to draw a definite conclusion due to methodological limitations. Favipiravir exposures during pregnancy should be followed up closely and the outcomes should be reported consistently.

7.
Pragmat Obs Res ; 13: 33-41, 2022.
Article in English | MEDLINE | ID: covidwho-1869279

ABSTRACT

Background: Favipiravir, an RNA-dependent RNA polymerase inhibitor (RdRp), is a broad-spectrum oral antiviral agent approved in India under emergency use authorization, for the treatment of mild-to-moderate coronavirus disease (COVID-19). The present study was planned to evaluate the effectiveness and safety of favipiravir in real-world clinical practice. Materials and Methods: This was a multicentric, retrospective, single-arm study conducted across four centres in India, after obtaining permission from the independent ethics committee. Medical records were analysed to evaluate effectiveness and safety of patients who were prescribed favipiravir. Results: The medical records of a total of 360 patients met the inclusion criteria, with 358 of them available for the final analysis. Males made up 58.46% of the study population. The average age of enrolled patients was 51.80 ± 16.45 years. The most common symptoms were fever, cough, and myalgia-fatigue. The median time to clinical cure and fever relief was five and four days, respectively. The average length of stay in the hospital was six days. In total, 8% of the patients experienced adverse events. Hepatic enzyme elevation, diarrhoea, decreased appetite, headache, fatigue, and giddiness were the common symptoms. Conclusion: In our real-world study, favipiravir was found to have a clinical cure rate of more than 90% in mild-to-moderate COVID-19 patients. This supports the use of favipiravir in the treatment of COVID-19. Favipiravir was well tolerated, with only minimal side effects, which were transient in nature.

8.
Turkish Archives of Pediatrics ; 57(3):372-373, 2022.
Article in English | EMBASE | ID: covidwho-1869996
9.
Pharmaceutical and Biomedical Research ; 7(4):257-266, 2021.
Article in English | EMBASE | ID: covidwho-1865955

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To increase the success in treating patients with COVID-19, many drug suggestions and some clinical studies are shared in the literature. However, the combination of several drugs with other clinical care has improved patients’ conditions. And this review discusses some side effects of Covid-19 drugs’ adverse effects. Objectives: Here, we have shortly reported the recent updates on the most common and plausible drugs for treating COVID-19 patients. We also compare these treatment options based on their impact on symptom management, inpatient length of stay, and overall morbidity and mortality. Methods: An extensive literature search was performed through PubMed, Scopus, Web of Science, and Google Scholar. Most of the keywords used were: "COVID-19", "Side effects of used drugs," "Treatment of COVID-19", "Risk factors," "Organ damage," and "Methods of diagnosis and treatment." Results: Anti-inflammatory, antimicrobial, and vitamin supplements do not have obvious benefits, but there is limited information to consider. Other factors and drugs such as improved plasma, eculizumab, immunoglobulins, IgG1-neutralizing monoclonal antibodies, remidseiver, steroids, and tosilizumab have shown potential effects on patient’s length of hospital stay and mortality. Currently, there is no evidence that any other vaccines, apart from those specifically designed for the SARS-Cov-2 virus, will protect against COVID-19. Conclusion: Since the prevention of the COVID-19 virus is a new issue in the medical world, there is no known effective treatment option in this area, and the prevention of its adverse side effects has not been conclusively proven. Of course, the occurrence of side effects in patients undergoing treatment such as hepatotoxicity, retinal damage, nephrotoxicity, and cardiotoxicity proves that the necessary caution should be used in drug combination methods.

10.
Letters in Drug Design and Discovery ; 19(5):413-427, 2022.
Article in English | EMBASE | ID: covidwho-1862452

ABSTRACT

Background: COVID-19, first reported in China, from the new strain of severe acute respiratory syndrome coronaviruses (SARS-CoV-2), poses a great threat to the world by claiming uncountable lives. SARS-CoV-2 is a highly infectious virus that has been spreading rapidly throughout the world. In the absence of any specific medicine to cure COVID-19, there is an urgent need to develop novel thera-peutics, including drug repositioning along with diagnostics and vaccines to combat the COVID-19. Many antivirals, antimalarials, antiparasitic, antibacterials, immunosuppressive anti-inflammatory, and immunoregulatory agents are being clinically investigated for the treatment of COVID-19. Objectives: The earlier developed one parameter regression model correlating the dock scores with in vitro anti-SARS-CoV-2 main protease activity well predicted the six drugs viz remdesivir, chloroquine, favipiravir, ribavirin, penciclovir, and nitazoxanide as potential anti-COVID agents. To further validate our earlier model, the biological activity of nine more recently published SARS-CoV-2 main protease inhibitors has been predicted using our previously reported model. Methods: In the present study, this regression model has been used to screen the existing antiviral, an-tiparasitic, antitubercular, and anti pneumonia chemotherapeutics utilizing dock score analyses to explore the potential including mechanism of action of these compounds in combating SARS-CoV-2 main prote-ase. Results: The high correlation (R=0.91) explaining 82.3% variance between the experimental versus predicted activities for the nine compounds is observed. It proves the robustness of our developed model. Therefore, this robust model has been further improved, taking a total number of 15 compounds to formu-late another model with an R-value of 0.887 and the explained variance of 78.6%. These models have been used for high throughput screening (HTS) of the 21 diverse compounds belonging to antiviral, an-tiparasitic, antitubercular, and anti pneumonia chemotherapeutics as potential repurpose agents to combat SARS-CoV-2 main protease. The models screened that the drugs bedaquiline and lefamulin have higher binding affinities (dock scores of-8.989 and-9.153 Kcal/mol respectively) than the reference compound {N}-[2-(5-fluoranyl-1~{H}-indol-3-yl)ethyl]ethanamide (dock score of-7.998 Kcal/Mol), as well as higher predicted activities with pEC50 of 0.783 and 0.937 µM and the 0.611 and 0.724 µM respectively. The clinically used repurposed drugs dexamethasone and cefixime have been predicted with pEC50 val-ues of-0.463 and-0.622 µM and-0.311 and-0.428 µM respectively for optimal inhibition. The drugs such as doxycycline, cefpodoxime, ciprofloxacin, sparfloxacin, moxifloxacin, and TBAJ-876 showed moderate binding affinity corresponding to the moderate predicted activity (-1.540 to-1.109 µM). Conclusion: In the present study, validation of our previously developed dock score-based one parametric regression model has been carried out by predicting 9 more SARS-CoV-2 main protease inhibitors. Another model has been formulated to explore the model's robustness. These models have been taken as a barometer for the screening of more potent compounds. The HTS revealed that the drugs such as bedaqui-line and lefamulin are highly predicted active compounds, whereas dexamethasone and cefixime have optimal inhibition towards SARS-CoV-2 main protease. The drugs such as doxycycline, cefpodoxime, ciprofloxacin, sparfloxacin, moxifloxacin, and TBAJ-876 have moderately active compounds towards the target inhibition.

11.
Clin Infect Pract ; 15: 100145, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1859406

ABSTRACT

Background: The novel coronavirus disease, commonly called COVID-19, has already killed millions of lives. Our study aimed to identify a safe and right drug for the management of such globally threatened COVID-19. Methods: This preliminary double-blinded randomized controlled trial was done among 57 hospitalized COVID-19 patients in the early stage of their illness. Of them, 29 patients received Favipiravir (FVP) and the remaining 28 patients received a placebo under the standard of care. Among the patients, 4 from Favipiravir (FVP) group and 3 from the placebo group were discontinued. The patients were observed regularly for a period of 10 days. Result: In our study, the FVP treated group showed accelerated viral clearance compared to the placebo-treated group. Assessment of chest X-ray showed remarkable improvement of pheumonia patient in group A compared to Group B. Hematological and Biochemical parameters such as total WBC count, neutrophil and lymphocyte counts were examined. No significant differences in the hematological parameters such as WBC count, neutrophil and lymphocyte counts in Group A and Group B patients. Liver transaminases levels were also stable in FVP treated group (average ALT ranges 39.4-46.2; AST 28.2-32.8). Conclusion: The drug Favipiravir displayed remarkable improvements in the clinical conditions and recovery of COVID-19 patients at the early stages of their infections.

12.
Biotechnol Lett ; 2022 May 24.
Article in English | MEDLINE | ID: covidwho-1859022

ABSTRACT

PURPOSE: In the wake of SARS-CoV-2's global spread, human activities from health to social life to education have been affected. Favipiravir and Molnupiravir exhibited novel hexokinase inhibition and we discuss advantages of this property in their COVID-19 inhibition potential. METHODS: This paper describes molecular docking data of human hexokinase II with Favipiravir, Cyan 20, Remdesivir, 2DG, and Molnupiravir along with hexokinase inhibition assays. RESULTS: Favipiravir, an antiviral drug previously cleared for treating the flu and ebola, has shown some promise in early trials to treat COVID-19. We observed potent human hexokinase inhibiting potential of Favipiravir (50%) as against 4% and merely 0.3% hexokinase inhibition with Molnupiravir and 2 Deoxy D glucose at 0.1 mM concentration supported by molecular docking studies. CONCLUSION: Favipiravir could continue to be part of the COVID-19 treatment regimen due to its resistance to host esterases, hexokinase inhibition potential and proven safety through human trials.

13.
Chemical Methodologies ; 6(6):463-474, 2022.
Article in English | Web of Science | ID: covidwho-1856523

ABSTRACT

The crystal structure of quinoline derivative with empirical formula (C18H21N3O7) was determined using single crystal X-ray diffraction, which belongs to the monoclinic system with the P2(1)/c space group. The cohesion and stabilization of the structure were provided by C-H center dot center dot center dot O hydrogen bond and Van-Der Waals interactions. A molecular docking study was performed to determine its antiviral potency between the SARS-CoV-2 main protease (M-pro) (PDB ID: 6Y2E) and chloroquine was chosen as a standard because of its similarity with our synthetic quinoline-based compound. Six herbal compounds and synthetic drugs bound to the active site of the target in order to compare their results with synthetic quinoline-based compound. This synthetic compound showed the lowest binding energy of -7.6 kcal.mol(-1), proving that this molecule seems to be a good candidate against the SARS-CoV-2.

14.
Acta Medica Nagasakiensia ; 65(2):67-71, 2021.
Article in English | EMBASE | ID: covidwho-1856303

ABSTRACT

The relationship between the severity of COVID-19, hyperinflammation, and intravascular coagulopathy is of critical importance. We report on a case of severe COVID-19 pneumonia treated with favipiravir during the earliest phase of the pandemic. The present case showed improvement in SARS-CoV-2 viral load and the presence of SARS-CoV-2 IgG with decreased radiological evidence of pulmonary infiltration. Moreover, the levels of serum IL-6 and TNF-α did not increase markedly. However, the hypoxia failed to recover, leading to the patient’s death due to possible pulmonary thrombosis, because D-dimer was markedly elevated, and an electrocardiogram showed typical changes. At present, the fact that some COVID-19 patients with mild to moderate symptoms suddenly die at home has become a major issue in Japan. These findings suggest that additional treatment with anti-coagulants should be considered in some COVID-19 patients at risk of hypercoagulation to prevent sudden death from pulmonary thrombosis.

15.
European Heart Journal Supplements ; 23(SUPPL F):1, 2021.
Article in English | Web of Science | ID: covidwho-1853052
16.
J Sep Sci ; 2022 May 18.
Article in English | MEDLINE | ID: covidwho-1850137

ABSTRACT

Favipiravir, molnupiravir, and ritonavir have been recently approved as the first oral antivirals for treatment of SARS-CoV-2 viral infections. Their combination was reported in several clinical studies, alternatively, to enhance the viral eradication and improve patient's recovery times and rates. Being all orally administered, therefore, the development of new sensitive and validated methodologies for their simultaneous determination is a necessitate. In the proposed research, a sensitive, selective, and simple high-performance thin layer chromatography method was developed and validated for determination of favipiravir, molnupiravir, and ritonavir. Silica gel 60F254 thin layer chromatography plates were used as stationary phase for this separation using mobile phase composed of methylene chloride:ethyl acetate:methanol:25% ammonia (6:3:4:1, v/v/v/v). Densitometric detection was performed at wavelength 289 nm. Peaks of favipiravir, molnupiravir, and ritonavir were resolved at retention factors 0.22, 0.42, and 0.63, respectively. The proposed method was found linear within the specified ranges of 3.75-100.00 µg/ml for molnupiravir and favipiravir, and 2.75-100.00 µg/ml for ritonavir. Limits of detection were found to be 1.12, 1.21, and 0.89 µg/ml for favipiravir, molnupiravir, and ritonavir, respectively. This is the first method to be reported for the simultaneous determination of the cited three antiviral drugs. The method was assessed on novel greenness metrics.

17.
J Evol Biochem Physiol ; 58(2): 430-440, 2022.
Article in English | MEDLINE | ID: covidwho-1846349

ABSTRACT

Introduction: Favipiravir and Vitamin C (Vit C) were used together in the treatment of the COVID-19 pandemic. However, the effects of favipiravir on the periodontium are still unknown. Therefore, the aim of this study was to investigate the effects of Favipiravir and Vit C treatment on alveolar bone metabolism. Experimental: Fifty healthy adult male Sprague-Dawley rats (2-3 months old) were randomly divided into five equal groups (n = 10): Control, Favi 20, Favi 100, Favi 20+Vit C, Favi 100+Vit C. Favipiravir (20 mg/kg and 100 mg/kg, i.m.) and Vit C (150 mg/kg/day, oral) were administered to the rats for 14 days. Alveolar bone loss (ABL) and histopathological changes were examined using a light microscope. Immunohistochemistry was used to determine levels of receptor activator of nuclear factor kappa-B ligand (RANKL), caspase-3, bone morphogenic protein 2 (BMP-2) and alkaline phosphatase (ALP) in the bone tissues. Results: Favipiravir increased the levels of RANKL and caspase-3 expression but decreased BMP-2 and ALP levels in a dose-dependent manner. Favi 20+Vit C and Favi 100 +Vit C groups showed decreased RANKL and caspase-3 levels in addition to increased BMP-2 and ALP levels. Conclusion: Favipiravir can cause histopathological damage to the periodontium, but administration of favipiravir combined with Vit C can provide a protective effect against this damage.

18.
Journal of Communicable Diseases ; 2022:258-262, 2022.
Article in English | Scopus | ID: covidwho-1848052

ABSTRACT

Background: Pharmacotherapy of Severe Acute Respiratory Corona Virus-2 (SARS-CoV-2), also denoted as COVID-19 is evolving. Many antivirals were found to be ineffective. Antiviral therapy used in 2020 was not originally developed for COVID-19. The effectiveness of favipiravir (an original drug for influenza) in COVID-19 pneumonia is questionable. Methods: A small sample retrospective study was conducted to indicate if favipiravir is effective in COVID-19 clearance. It was conducted in a tertiary-level care hospital in the United Arab Emirates. COVID-19 pneumonia patients were admitted to the hospital from January to December 2020 were studied. SPSS version 26 was used for the data analysis. Results: The average day of COVID-19 clearance for those who received favipiravir alone or favipiravir and hydroxychloroquine together were 12 days. Those who received no antivirals had COVID-19 clearance in an average of 11 days. Independent-Samples Kruskal-Wallis Test shows no statistically significant difference (p-value 0.663) in the length of COVID-19 clearance between these three treatment groups. Conclusion: Favipiravir was not effective in mild COVID-19 pneumonia for achieving COVID-19 clearance. The effectiveness of favipiravir on COVID-19 clearance needs to be studied further. Copyright (c) 2022: Author(s).

19.
Bioscientia Medicina ; 5(10):949-952, 2021.
Article in English | GIM | ID: covidwho-1836513

ABSTRACT

Background: Delirium is a common condition in geriatric patients. One of the trigger factors for this condition is an infection, such as COVID-19 infection. Elderly with COVID-19 show atypical symptoms such as delirium. Elderly patients with COVID-19 who present with delirium, either as a primary symptom or showing symptoms or signs, have a poor prognosis. This study were aimed to presents covid-19 elderly patient with comorbid delirium. Case presentation: A 77-year-old woman with disorientation for one day came to Emergency Department with her family. She had no history of headaches, blurred vision, or seizures. However, she had a fever, did not want to eat for three days, and had a purulent decubitus ulcer. The patient was diagnosed with acute delirium syndrome, confirmed COVID-19 with sepsis, malnutrition, hypercoagulation, grade III decubitus ulcer, suspected dementia, immobilization, total dependence. The patient admitted to the isolation ward. The patient had meropenem 500 mg every 12 hours, anticoagulants and favipiravir according to the dose and parenteral nutrition.

20.
Viruses ; 14(4)2022 03 24.
Article in English | MEDLINE | ID: covidwho-1834918

ABSTRACT

The effect of treatment with favipiravir, an antiviral purine nucleoside analog, for coronavirus disease 2019 (COVID-19) on the production and duration of neutralizing antibodies for SARS-CoV-2 was explored. There were 17 age-, gender-, and body mass index-matched pairs of favipiravir treated versus control selected from a total of 99 patients recovered from moderate COVID-19. These subjects participated in the longitudinal (>6 months) analysis of (i) SARS-CoV-2 spike protein's receptor-binding domain IgG, (ii) virus neutralization assay using authentic virus, and (iii) neutralization potency against original (WT) SARS-CoV-2 and cross-neutralization against B.1.351 (beta) variant carrying triple mutations of K417N, E484K, and N501Y. The results demonstrate that the use of favipiravir: (1) significantly accelerated the elimination of SARS-CoV-2 in the case vs. control groups (p = 0.027), (2) preserved the generation and persistence of neutralizing antibodies in the host, and (3) did not interfere the maturation of neutralizing potency of anti-SARS-CoV-2 and neutralizing breadth against SARS-CoV-2 variants. In conclusion, treatment of COVID-19 with favipiravir accelerates viral clearance and does not interfere the generation or maturation of neutralizing potency against both WT SARS-CoV-2 and its variants.


Subject(s)
Antibodies, Neutralizing , COVID-19 , SARS-CoV-2 , Amides/therapeutic use , Antibodies, Neutralizing/metabolism , Antibodies, Viral , COVID-19/drug therapy , Humans , Immunoglobulin G , Neutralization Tests , Pyrazines/therapeutic use , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
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