(D) Immunoprobing of bromelaintreated purified Sectodomain (1:10 ratio) with 30, 60, 120, and 240 min. Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection.Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19.Methods: This was an open . eTh procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. All participants were evaluated with nasopharyngeal swab polymerase chain reaction (PCR) and chest computed tomography (CCT). Quintremil S , Transcriptional and epigenetic regulation of macrophages in atherosclerosis. View this study on Beta.ClinicalTrials.gov, U.S. Department of Health and Human Services, The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. , et al. A sample size calculation was performed based on our observed results by using a one-sided McNemars test. et al. , , , For this reason, a combination of quercetin and vitamin C is recommended in severe infections where the body is under stress (Kim et al., 2013). et al. It can cause endothelial dysfunction, hypercoagulability, and cytokine storm (Potus et al., 2020). Fact check: Over-the-counter vitamins for COVID-19 are unproven - USA TODAY Alcocer S (I) SPR Max Resonance Units (RSU) at equilibrium as a function of the concentration of control RBD and Sectodomain using immobilized ACE2. Therefore, those findings may be explained by the immune-modulatory properties of flavonoids on macrophages via contributing their transformation from pro- to antiinflammatory phenotypes (Conti et al., 2020). et al. , Ackermann M , The endpoint was that QCB supplementation was continued throughout the follow-up period from study baseline to discharge, intubation, or death. ). Studies suggest 4 vitamins to lower risk of severe cases of COVID-19 , Lucas SB Aggarwal A The decrease in CRP and ferritin levels was higher in the QCB group (all Ps were < 0.05). , 2021 Jan;16(1):74-81. doi: 10.1097/COH.0000000000000658. None of the adverse effects related to QCB supplement was observed in participants. The combination of bromelain and curcumin as an immune Stevens JM , Trimaille A Bsmller H Bonilla E Luo C , Naturally, an insufficiency of vitamin C leads to severe injuries to multiple organs, especially to the heart and brain, since they are both highly aerobic organs that produce more oxygen radicals. Carmichael MD , (C) Immunofluorescence of Sectodomain invehicle, bromelain (75 g/ml) with and without E64 (4 M)treated VeroE6 cells (n = 3) for 2 h. Nuclei were stained with DAPI. Omaha Bromelain and Acetylcysteine (BromAc) has synergistic action against glycoproteins by breakage of glycosidic linkages and disulfide bonds. -, Zhu F.C., Guan X.H., Li Y.H., Huang J.Y., Jiang T., Hou L.H., Li J.X., Yang B.F., Wang L., Wang W.J., et al. 3E and F). Besides, QCB supplement is suggested to have a role on the elevation of the thrombocyte and lymphocyte count. 8 1I intent). , In the QCB group, the increase in platelet and lymphocyte counts was higher (all Ps were < 0.05). 2019. , ( US Food and Drug Administration described quercetin as GRAS status (generally recognized as safe) (Davis et al., 2009). 3A and B) and was further confirmed by cysteine protease inhibitor (E64) treatment (Fig. FOIA 1H). 2013. Needs PW Selective inhibitors of picornavirus replication. official website and that any information you provide is encrypted It differs between individuals, and also reinfection of individuals with SARSCoV2. Chen J Bromelain Inhibits SARS-CoV-2 Infection in VeroE6 Cells - PMC Cardiovascular Disease: A Target for the Pharmacological Eefcts of Quercetin. , Pharmacokinetics and bioavailability of the flavonol quercetin in humans, Int Journal of Clinical Pharmacology and eThrapeutics. , Role of Oxidative Stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) Infection: A Review. Prakash Radhakrishnan conceived the idea; Surender Khurana, St. Patrick M. Reid, Gloria E. O. Borgstahl, and Prakash Radhakrishnan designed research; Satish Sagar, Ashok Kumar Rathinavel, William E. Lutz, Lucas R. Struble, St. Patrick M. Reid, Tobias Hoffmann, and Mara J. Broadhurst performed research; Nitish Kumar Mishra, Chittibabu Guda, Nicholas Y. Palermo, and Kenneth W. Bayles contributed new reagents/analytic tools; Satish Sagar, Ashok Kumar Rathinavel, Andy T. Schnaubelt, Gloria E. O. Borgstahl, St. Patrick M. Reid, and Prakash Radhakrishnan analyzed data; Gloria E. O. Borgstahl, and Prakash Radhakrishnan wrote the paper. We suggest that suboptimal bioavailability of QCB may explain this situation. Curth U , 1 , doi: 10.7759/cureus.27876. Department of General Surgery, stanbul Kanuni Sultan Sleyman Training and Research Hospital, stanbul, , 2015. et al. Exclusion criteria determined as severe respiratory failure, shock and combined failure of other organs that required ICU (intensive care unit) monitoring and treatment, previous history of allergic reactions against any component of QCB, pregnant or lactating women, women of childbearing age with a positive pregnancy test, breastfeeding, miscarriage, or within 2 weeks after delivery, and participation in another clinical trial against SARS-CoV-2 treatment currently or in the past 28 days. Quercetin as a possible complementary agent for early-stage COVID-19 With the advantage of the lack of systemic toxicity, flavonoids, including quercetin are proven to potentialize the effects of routine drugs against coronavirus (Ferrer et al., 2008). QUERCETIN Reviews and User Ratings: Effectiveness, Ease of Use, and , et al. Nausea. Chen C Jesel L ). Bayshnikova E 2020. Number 3: Zinc stops viral replication multiple ways, so . Flow chart of the study was demonstrated as Figure-1 (Figure 1). , Mean SD (n = 3). Salazar J official website and that any information you provide is encrypted Quercetin is a safe natural anti-oxidant and anti-inflammatory polyphenolic compound that found in various natural sources include onion, red grapes, honey and citrus fruits. , Surface plasmon resonance (SPR) analysis revealed that purified SARSCoV2 Sectodomain binds with ACE2 in a concentrationdependent manner and has a comparable binding affinity as control RBD (Fig. Read our, ClinicalTrials.gov Identifier: NCT04468139, Interventional , Before , Nasopharyngeal swab SARS CoV2 PCR result was positive in 40%50% of cases for both groups (p = 0.84; Table 3). , Sage T In the standard treatment group, 8/380 patients required intensive care due to respiratory failure. ( Natural products may help to reduce your hay fever - PressReader ). ). , 2020. SectodomaineGFP purified from Tni insect cells and showed 215 kDa molecular weight (intent; 1, mock control; 2, SectodomaineGFP). Shi Y, Zeida A, Edwards CE, Mallory ML, Sastre S, Machado MR, Pickles RJ, Fu L, Liu K, Yang J, Baric RS, Boucher RC, Radi R, Carroll KS. ( Malenfant S , , Moreover, mast cell degranulation associated with interstitial edemaand immunothrombosis was just reported in alveolar septa of deceased patients with COVID-19 (Motta Junior et al., 2020). Demographic features, vital signs, laboratory test results during follow-up, drug administration data, past, and current diagnoses of the patients were recorded. Nagashima S , We sought to determine the effect of BromAc on the spike and envelope proteins and its potential to reduce infectivity in host cells. 8600 Rockville Pike Di Santo S Mano JF Bartosz G Pavan R , Quercetin Information | Mount Sinai - New York Mast Cells in Alveolar Septa of COVID-19 Patients: A Pathogenic Pathway aTht May Link Interstitial Edema to Immunothrombosis. Listing a study does not mean it has been evaluated by the U.S. Federal Government. , The .gov means its official. Bromelain and Acetylcysteine (BromAc) has synergistic action against glycoproteins by breakage of glycosidic linkages and disulfide bonds. Raiser W Our docking studies between homotrimeric (RBD containing chain A) S protein and stem bromelain revealed that bromelain cleaves the Sprotein equally likely at the 131166 (50.4%) and 617649 (49.6%) disulfide bonds (Fig. Jiang F ). All Rights Reserved, NAC may also protect against coagulation problems associated with COVID-19, as it has both. The Combination of Bromelain and Acetylcysteine (BromAc Epub 2020 Oct 26. et al. 2022 Dec 20;24(1):20. doi: 10.3390/ijms24010020. ). , In the literature, platelet activation and aggregation have been reported in patients with severe COVID-19, but the triggers of these processes are not discussed yet (Hottz et al., 2020; Salamanna et al., 2020). You have reached the maximum number of saved studies (100). official website and that any information you provide is encrypted 2005. , Viral particles treated with vehicle control (left) and bromelain (right). Materials are available upon a reasonable request from the corresponding author. Eefct of quercetin and other flavonoids on antigeninduced histamine secretion from rat intestinal mast cells. Oral steroids are used on and after the fifth day for pulmonary weakness and aspirin or NAC can be added to reduce the risk of clotting. Treatment of COVID-19 patients with quercetin: a prospective, single Department of Genetics, Editorial: Emerging and old viral diseases: Antiviral drug discovery from medicinal plants. Monocytes play a critical role in the inflammatory response. Manach C ). , , Omaha Centre for Biological Threats and Special Pathogens 4 (ZBS 4), Conti P et al. The most common complaints at the time of hospital admission were fatigue (62.4%), cough (61.1%), anorexia (57%), thirst (53.7%), respiratory distress (51%) and chills (48.3%). Maddipati KR , Computer-generated random numbers were used for simple randomization. (G) Negativestaining transmissionEM of bromelaintreated (250 g /ml, at 37C for 1.5 h) SARSCoV2. Upon this data, the investigators hypothesize that quercetin can be effective on both prophylaxis and treatment of COVID-19 cases. Baena CP Although there was no significant difference between the two groups in terms of reduction in D-Dimer levels with treatment, in the standard treatment group, 3/380 patients required intensive care due to stroke, 2/380 patients due to myocardial infarction, and 1/380 patients due to delirium (Table 4, Figure 2). 2020. Clipboard, Search History, and several other advanced features are temporarily unavailable. USA, 2 , et al. Since bromelain inhibits SARSCoV2 infection, and its profound fibrinolytic activity The combination of bromelain and curcumin as an immune-boosting Castellani ML ). Bromelain inhibits SARSCoV2 binding and infection. 2006. ). HHS Vulnerability Disclosure, Help In terms of comorbid diseases, the standard treatment plus QCB group had a significantly higher number of chronic obstructive pulmonary disease (COPD, p = 0.02), though there was no significant difference in terms of other diseases. The https:// ensures that you are connecting to the Studies have demonstrated that SARSCoV2 Sprotein has high homology among other coronaviruses (76% identity with SARSCoV) with conserved cysteine amino acids (UniProtKB: {"type":"entrez-protein","attrs":{"text":"P59594","term_id":"30173397","term_text":"P59594"}}P59594). The wild-type (WT) SARS-CoV-2 strain at 5.5 and 4.5 log. Labratory parameters of all patients at the time of admission. et al. - January 26, 2023. , An official website of the United States government. Researchers have been applying computer modeling techniques to identify molecules with structures that could conceivably block the "ACE2 receptors" on cells to which the coronavirus that causes COVID-19 attaches, much like a key fits into a lock. Anti-inflammatory potential of Quercetin in COVID-19 treatment Therefore, we conclude that further studies involving different doses and plasma level measurements are required to reveal the dose/response relationship and bioavailability of QCB for a better understanding of the role of QCB in the treatment of SARS CoV-2. We sought to determine the effect of BromAc on the spike and envelope proteins and its potential to reduce infectivity in host cells. , Xu W , , To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Zaim S, Chong JH, Sankaranarayanan V, Harky A. ACE2 expression in kidney and testis may cause kidney and testis damage after 2019nCoV infection, Discovering drugs to treat coronavirus disease 2019 (COVID19), Recent progress and challenges in drug development against COVID19 coronavirus (SARSCoV2): an update on the status, Perioperative bromelain reduces pain and swelling and improves quality of life measures after mandibular third molar surgery: a randomized, doubleblind, placebocontrolled clinical trial, Fibrinolytic and antithrombotic action of bromelain may eliminate thrombosis in heart patients, A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study. Struijs K Heat inactivation and cysteine proteinase inhibitor (E64) treatment inhibited bromelain mediated digestion of Sectodomain (Fig. Accessibility , Kumazawa Y Also, thrombosis development is a significant risk factor of multiorgan failure and death in COVID19 patients. Most importantly, VeroE6 cells or SARSCoV2 or both with bromelain reduces the viral infection (Fig. Most recently, platelets were reported to trigger degranulation of perivascular mast cells leading to inflammatory responses and tissue injury (Karhausen et al., 2020). Mustafa MR, Antiviral activity of four types of bioflavonoid against dengue virus type-2. Al Shukor N The Therapeutic and Prophylactic Potential of Quercetin against COVID doi: 10.1126/science.abd4251. The https:// ensures that you are connecting to the J. Antimicrob. Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection, Vitamin C deficiency increases the lung pathology of inuflenza virus-infected gulo-/- mice. The Cq values were graphically represented. Bethesda, MD 20894, Web Policies Therefore, we suggest that the combination of quercetin and standard anticoagulant therapy can also create a synergistic effect. Quercetin suppresses the NLRP3 inflammasome by affecting these regulators. , Information provided by (Responsible Party): Amr kamel khalil Ahmed, Ministry of Health, Saudi Arabia, Quercetin 500 g of quercetin Quercetin will be administered orally once daily, in the morning before breakfast for 5-10 days or patient improves or discharged, Dietary Supplement: Quercetin Treatment a daily dose of quercetin (500 mg) will be taken orally by proven COVID-19 cases intervention, Dietary Supplement:Bromealin Treatment a daily dose of bromelain(500 mg) will be taken orally by proven COVID-19 cases intervention, zinc 50 mg orally daily dose will be taken orally by proven COVID-19 cases intervention, vitamin c 1000 mg orally daily by proven COVID-19 cases intervention, speed the days of recovery and discharge from hospital, the level of serum zinc is very important especially at chronic diseases, according to questionnaire including BMI, smoking , underlying diseases like hypertension, diabetes , asthmatic , ..etc, day of negative conversion for nasopharyngeal swab for rt-PCR FOR covid-19. After adjustment for the conditions (CCT lung involvement stage, oxygen saturation, favipiravir use, presence of comorbid chronic disease), similar results were observed between the groups (statistically significantly different values were persisted same as the previous). Low OD would signify important cell lysis due to virus replication. 2H). Karhausen J Further, SARSCoV2 with bromelain treatment showed the loss of Spike protein on the viral surface (Fig. Morris ME Hence, quercetin is thought to be a good candidate to enhance the impact of routine treatment of COVID-19. Data points correspond to area under the curve analysis of normalized cell index (electronic impedance of RTCA established at time of inoculation) at 12-h intervals. 2022 Aug 11;14(8):e27876. Properties and therapeutic application of bromelain: a review. Quercetin: Health benefits, dosage, and side effects , , Oral supplementation with quercetin up to 1 g/day for 3 months has not resulted in significant adverse effects (Harwood et al., 2007). suggests that bromelain or bromelainrich pineapple could be used as an antiviral against SARSCoV2 and future outbreaks of other coronaviruses. Accessibility Pulmonary findings at the time of hospital admission in the standard therapy plus QCB group were significantly more severe than in the standard therapy group (p = 0.03; Table 3). ( , Boots AW 2B and C) and purified Sectodomain (Fig. Distinct conformational states of SARS-CoV-2 spike protein. 3 Teixeira L , 1E) and ACE2 negative normal bronchial epithelial (BEAS2B) and lung adenocarcinoma (A549) cells (Fig. , Collectively, these results suggest that bromelain could inhibit SARSCoV2 binding and infection in VeroE6 and Calu3 cells. (B and C) Immunoblotting of Sectodomain in bromelaintreated Tni insect cell supernatant varying dose (5, 10, 15, 20, and 25 g/mg of total protein) and time (25 g/mg of total protein for 1060 min), respectively. Epub 2021 Jul 26. Therefore, we conclude that further studies involving different doses, and plasma level measurements are required to reveal the dose/response relationship and bioavailability of QCB for a better understanding of the role of QCB in the treatment of SARS CoV-2. Takimoto H and cancer. ( Comparison of groups in terms of laboratory parameters. The major benefit of taking quercetin with zinc is that the quercetin will push the zinc into the . FOIA 2020. , Ishitsuka H Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved -ketoamide inhibitors. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. ). Bae S , Careers, Unable to load your collection due to an error. Cell Biology and Anatomy, Proc Natl Acad Sci U S A. , -, Folegatti P.M., Ewer K.J., Aley P.K., Angus B., Becker S., Belij-Rammerstorfer S., Bellamy D., Bibi S., Bittaye M., Clutterbuck E.A., et al. ( Schlechter BL the contents by NLM or the National Institutes of Health. , "When paired with. 2E and F). In a previous study, a rate of lymphopenia in 35%, thrombocytopenia in 12%, elevated CRP in 86%, increased LDH in 76%, elevated D-Dimer in 36% and increased ferritin in 63% were detected (Chen N et al., 2020). 2020. Antioxidant polyphenols in cancer treatment: Friend, foe or foil? sharing sensitive information, make sure youre on a federal The primary endpoint of the study was determined as QCB supplementation was continued throughout the follow-up period from study baseline to discharge, intubation, or death. USA, 4 This mechanism of the virus emerged as a target for several anti-viral therapies. Ogra PL Structural basis of severe acute respiratory syndrome coronavirus 2 infection. , , When oral quercetin is taken 500 mg, the maximum plasma concentration is reached within 4 h (Moon et al., 2008). Choi HW Puelles VG Therefore, quercetin seemed to have the most ACE inhibiting capacity between all flavonoids. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Flavonoids owe their antioxidant, anti-inflammatory and anti-viral properties against a wide range of DNA and RNA viruses, to their pleiotropic molecular structure that acts by targeting variable cells on multiple pathways (Puelles et al., 2020). Results of a recent research endeavor from the United States indicate that bromelain or bromelain rich pineapple stem may be utilized as an antiviral agent against coronavirus disease. Ltgehetmann M Vitamin C with quercetin benefits for inflammation, COVID, heart ( , , Cao W In our study, lymphopenia was detected in 20.7% of the cases, thrombocytopenia in 4.2%, high CRP in 32.6%, LDH in 54.3%, D-Dimer in 26.3% and Ferritin in 31.3% (Table 2). Abdominal pain. Detailed materials and methods and key resources are included in the supplementary information. Berlin Turkey, 3 , Snchez M sharing sensitive information, make sure youre on a federal Bell AS Russo GL The recommended treatment regimen is hydroxychloroquine, 400 mg daily for another 5 days, and favipiravir, 2 600 mg for 4 days following a 2 1600 mg loading dose on day one. ( ). , Rodrigo R New England Journal of Medicine. Pignatelli P Computed tomography (CT) images of hospitalised patients with complications of COVID 19 reveal the presence of pneumonia with evidence of pulmonary ground-glass opacities, and severe cases may progress to ARDS and acute cardiac damage (Lei et al., 2020). et al. Most people with COVID 19 develop only mild (40%) or moderate (40%) disease; approximately 15% develop severe disease that requires oxygen support, and 5% have critical disease with complications such as respiratory failure, acute respiratory distress syndrome (ARDS), sepsis and septic shock, thromboembolism, and/or multiorgan failure, including acute kidney injury and cardiac injury. 2020. 5 Hberle H The study was reported according to the Consolidated Standards of Reporting Trials guidelines and registered on ClinicalTrials.gov (number: {"type":"clinical-trial","attrs":{"text":"NCT04377789","term_id":"NCT04377789"}}NCT04377789) on March 20, 2020. ( Additionally, we found significantly reduced SARSCoV2 viral RNA copies in bromelaintreated VeroE6 (P = .0010) and Calu3 (P = .0099) cells (Fig. , ). ). Palhinha L Flavonoids have the ability to modulate macrophages from pro- to anti-inflammatory phenotypes, potentially contributing to the resolution of preestablished inflammatory processes (Mendes et al., 2019). de Winther MPJ Epub 2022 Feb 25. Molecular and functional resemblance of dexamethasone and quercetin: A P < .05 was considered statistically significant with an unpaired Student's ttest. Federal government websites often end in .gov or .mil. The Ministry of Health and local ethics committee approved the study (Ethics Committee approval number: KAEK/2020.05.50). ). ). Moon YJ 2008. , Computational Chemistry Core, Ballotta A In this study, most common symptoms at presentation were fatigue (62.5%), cough (60.4 %), anorexia (56.6%), thirst (54.3%), respiratory distress (51%), and chills (48.3%), respectively (Table 1). Alterations in acute phase reactants and complete blood count parameters during the follow-up. The mean fluorescent intensity was measured by using FlowJo software. ( 2020;56:106080. doi: 10.1016/j.ijantimicag.2020.106080. Quercetin 800 mg, bromelain 165 mg, zinc acetate 50 mg and ascorbic acid 1 g once daily supplements were safe for patients infected with SARS-CoV-2 and may prevent poor prognosis. Though the catalytic site is not directly engaged, proteinprotein docking places the enzyme in close proximity to these bonds. Lancet. , Quercetin, Bromelain and NAC for COVID (2023) By Dr Frank Yap, M.D. Yartey N Routine care versus QCB (quercetin, vitamin C, bromelain) supplementation was compared between 429 patients with at least one chronic disease and moderate-to-severe respiratory symptoms. Carafa A Carnevale R Hence, a combination of quercetin, vitamin C and bromelain was preferred in this study, and none of the advers effects related to QCB supplement was observed in participants. , Biomed Pharmacother. USA, 3 Vitamin C Is an Essential Factor on the Anti-viral Immune Responses through the Production of Interferon-/ at the Initial Stage of Inuflenza A Virus (H3N2) Infection. These two results indicated that purified Sectodomain is a properly folded and functionally active protein. et al. et al. (A and B) Immunoprobing of ACE2 and TMPRSS2 expression in various normal and cancerous cells. 2020. , , , Quercetin has been shown to inhibit its proteolytic activity by binding to virus-specific protease (Chen et al., 2006). Department of Pediatric Nutrition and Metabolism Clinics, stanbul Kanuni Sultan Sleyman Training and Research Hospital, stanbul, Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19. Therefore, quercetin could have antiviral activity against many RNA viruses . In fact, studies of in vivo effect on vitamin C are difficult since most animals, except human and some primate, are capable of synthesizing vitamin C endogenously. The decrease in the levels of C-reactive protein and ferritin was significantly higher in the group that received standard treatment plus QCB compared to the other group (Pcrp = 0.001; Pferritin = 0.033; Table 4, Figure 2). This chemical compound ( flavonoid ) is naturally found in foods including apples, onions, teas, berries, red wine, and herbs like ginkgo biloba and St. John's wort. Valente M Hubbard GP , Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04468139, We're building a modernized ClinicalTrials.gov!
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