Analgesics
Antiandrogens
Antihistamines
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
PPIs
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
 
next
study
previous
study
c19early.org COVID-19 treatment researchAntiandrogensAntiandrogens (more..)
Melatonin Meta
Metformin Meta
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta PPIs Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis       

13 cis retinoic acid improved the outcomes of COVID-19 patients. A randomized clinical trial

Elkazzaz et al., medRxiv, doi:10.1101/2022.03.05.22271959, NCT04353180
Mar 2022  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
Mortality 86% Improvement Relative Risk ICU admission 67% Recovery time 35% Time to viral- 44% Isotretinoin  Elkazzaz et al.  LATE TREATMENT  RCT Is late treatment with antiandrogens beneficial for COVID-19? RCT 40 patients in Egypt (June - August 2020) Faster recovery (p<0.0001) and viral clearance (p<0.0001) c19early.org Elkazzaz et al., medRxiv, March 2022 Favorsisotretinoin Favorscontrol 0 0.5 1 1.5 2+
7th treatment shown to reduce risk in September 2020, now with p = 0.000000056 from 49 studies.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
RCT with 20 13-cis-retinoic acid patients and 20 control patients, showing faster recovery and viral clearance with treatment. Aerosolized 13-cis-retinoic acid with increasing dose from 0.2 mg/kg/day to 4 mg/kg/day for 14 days, plus oral 13-cis-retinoic acid 20 mg/day. 13-cis retinoic acid, also known as isotretinoin, is a synthetic vitamin A derivative that has been shown to have antiandrogenic effects.
risk of death, 85.7% lower, RR 0.14, p = 0.23, treatment 0 of 20 (0.0%), control 3 of 20 (15.0%), NNT 6.7, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of ICU admission, 66.7% lower, RR 0.33, p = 0.24, treatment 2 of 20 (10.0%), control 6 of 20 (30.0%), NNT 5.0.
recovery time, 35.4% lower, relative time 0.65, p < 0.001, treatment mean 16.3 (±4.5) n=20, control mean 25.23 (±4.72) n=20.
time to viral-, 44.0% lower, relative time 0.56, p < 0.001, treatment mean 13.36 (±1.49) n=20, control mean 23.85 (±4.0) n=20.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Elkazzaz et al., 8 Mar 2022, Randomized Controlled Trial, Egypt, preprint, 4 authors, study period June 2020 - August 2020, trial NCT04353180 (history).
This PaperAntiandrogensAll
STRA6 (vitamin A receptor), as a Novel binding receptor of COVID-19 (A breakthrough)
Mahmoud Elkazzaz, Tamer Haydara, Yousry Esam-Eldin Abo-Amer, Israa M Shamkh, Mohammed . F Abo El Magd, Amr Ahmed
doi:10.21203/rs.3.rs-892203/v3
Background A global pandemic of pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, at the end of 2019. Although, the ACE2 receptor has been demonstrated to be the main entry receptor of COVID-19, but our docking analysis , predicted and discovered a novel receptor termed STRA6 that may play a critical role in the pathogenicity of COVID-19 and explain the common pre and post COVID-19 symptoms with unknown etiology. STRA6 receptor expressed in many organs and immune cells, upregulated by retinoic acid jm6 (STRA6) was the rst protein to be identi ed in a novel category of proteins, cytokine signaling transporters, due to its ability to function as both a cell surface receptor and a membrane protein that binds to retinol binding protein facilitating cellular uptake of retinol. The primary ligand of STRA6 (vitamin/retinol) was shown to be drastically reduced during COVID-19 infection, which agrees with our ndings. Methods The STRA6 receptor protein were submitted to the server for functional interaction associated network between partners for the STRING (Research Online of Interacting Genes/Proteins Data Basis version 10.0)13 .Docking study of each Spike -ACE 2 and STRA6 receptor protein were carried out using HDOCK server (http://hdock.phys.hust.edu.cn/). The binding mode of Spike -ACE 2 and STRA6 receptor protein is retrieved form the PDB https://www.rcsb.org/ with accession number (7DMU , 5sy1) Results Surprisingly, our molecular docking based analysis showed that spike protein Receptor Binding Domain(RDB) of COVID-19 strongly and e ciently binds to STRA6 receptor, de nitely to the RDB vital residues of RBP-binding motif located in STRA6 receptor. STRA6 receptor is a membrane receptor responsible for signaling and transporting of Vitamin A(Retinol) from plasma retinol binding protein (RBP) to our cells. In an outstanding manner, COVID-19 Spike protein exhibited high docking score with human STRA6 with low binding energy . The docking score of COVID-19 spike protein was stronger than the docking score of spike protein with ACE2.The surface view of complex reveals that the binding pocket of STRA6-Spike protein and Spike ACE 2 complexes with RMSD (189.44 Å , 1.00 Å ) representatively and docking score (-341.21 ,-354.68) kcal/mol the quality of the receptor and the ligand are LGscore and MaxSub ( 2.416 , 0.147 ). The spike to bind to RDB of the STRA 6 protein in the ILE 131C , MET 145C , HIS 86A with interface residue( 4.961 , 4.953 and 3.271) representatively. In conclusion STRA6 mutations results in a broad spectrum of complication related to malformations including congenital heart defects , anophthalmia, alveolar capillary dysplasia, diaphragmatic hernia, lung hypoplasia and mental retardation. Moreover, Retinoic acid metabolism is defective in COVID-19 (cytokine storm), sepsis, ARDS and SIRS. Therefore, we believe that this novel discovery that STRA6 receptor acts as a novel binding..
Declarations Con ict of Interest Statement The author declares that the research was conducted in the absence of any commercial or nancial relationships that could be construed as a potential con ict of interest. The spike to bind to RD8 of the STRA 6 protein
References
-Babon, Varghese, Nicola, Inhibition of IL-6 family cytokines by SOCS3, Seminars in immunology, doi:10.1016/j.smim.2013.12.004
-Chen, Clarke, Kim, Stowe, Kim et al., Structure of the STRA6 receptor for retinol uptake, Science, doi:10.1126/science.aad8266
-Devaprasad, Pandit, Enrichment of SARS-CoV-2 entry factors and interacting intracellular genes in peripheral immune cells, bioRxiv, doi:10.1101/2021.03.29.437515
-Fedders, Muenzner, Schupp, Retinol binding protein 4 and its membrane receptors: a metabolic perspective, HormMolBiolClin Invest
-Johnson, Lewin, Ahmed, SOCS, Intrinsic Virulence Factors, and Treatment of COVID-19, Front Immunol, doi:10.3389/mmu.2020.582102
-Karunanithi, Sheelarani, RBP4-STRA6 Pathway Drives Cancer Stem Cell Maintenance and Mediates High-Fat Diet-Induced Colon Carcinogenesis, Stem cell reports, doi:10.1016/j.stemcr.2017.06.002
-Kelly, Johannes Von Lintig, STRA6: role in cellular retinol uptake and e ux, Hepatobiliary surgery and nutrition, doi:10.3978/j.issn.2304-3881.2015.01.12
-Merad, Martin, Pathological in ammation in patients with COVID-19: a key role for monocytes and macrophages, Nat Rev Immunol, doi:10.1038/s41577-020-0331-4
-Norseen, Hosooka, Hammarstedt, Yore, Kant et al., Retinol-binding protein 4 inhibits insulin signaling in adipocytes by inducing proin ammatory cytokines in macrophages through a c-Jun N-terminal kinase-and toll-like receptor 4-dependent and retinol-independent mechanism, Mol Cell Biol, doi:10.1128/MCB.06193-11
-Pino-Lagos, Benson, Noelle, Retinoic acid in the immune system, Ann N Y Acad Sci, doi:10.1196/annals.1443.017
-Raverdeau, Mills, Modulation of T cell and innate immune responses by retinoic Acid, J Immunol
-Ross, Stephensen, Kim, Control of Innate and Adaptive Lymphocytes by the RAR-Retinoic Acid Axis, Immune Netw, doi:10.4110/in.2018.18.e1
-Ruan, Yang, Wang, Jiang, Song, Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China, Intensive Care Medicine, doi:10.1007/s00134-020-05991-x
Barclay, Anderson, Waters, Curlewis, SOCS3 as a tumor suppressor in breast cancer cells, and its regulation by PRL, Int J Cancer, doi:10.1002/ijc.24172
Barrett, Human Peripheral Blood Mononuclear Cells Express High Levels of the Vitamin a Transport Protein, Stimulated by Retinoic Acid 6 (P19-004-19, Current Developments in Nutrition, doi:10.1093/cdn/nzz049.P19-004-19
Berry, Daniel, Signaling by vitamin A and retinol-binding protein regulates gene expression to inhibit insulin responses, Proceedings of the National Academy of Sciences of the United States of America, doi:10.1073/pnas.1011115108
Berry, Jin, Majumdar, Noy, Procnatlacadsci, Signaling by vitamin A and retinol-binding protein regulates gene expression to inhibit insulin responses
Bouillet, Sapin, Chazaud, Messaddeq, Décimo et al., -Developmental expression pattern of Stra6, a retinoic acid-responsive gene encoding a new type of membrane protein, Mech Dev
Chassaing, Golzio, Odent, Lequeux, Vigouroux et al., None, Hum Mutat
Croker, Krebs, Zhang, Wormald, Willson et al., SOCS3 negatively regulates IL-6 signaling in vivo, Nat Immunol, doi:10.1038/ni931
Huang, Su, Theron, Wu, Lai et al., An interferon-gamma-related cytokine storm in SARS patients, J Med Virol, doi:10.1002/jmv.20255
Isken, Golczak, Oberhauser, Hunzelmann, Driever et al., -RBP4 disrupts vitamin A uptake homeostasis in a STRA6-de cient animal model for Matthew-Wood syndrome, J Cell Metab
Kam, Deng, Chen, Retinoic acid synthesis and functions in early embryonic development, Cell Biosci, doi:10.1186/2045-3701-2-11
Kawaguchi, Yu, Ter-Stepanian, Zhong, Cheng et al., None, Chem Biol
Nair, Sugunan, Kumar, Anilkumar, -Case-control analysis of SNPs in GLUT4, RBP4 and STRA6: association of SNPs in STRA6 with type 2 diabetes in a South Indian population, PLoS One
Ng, Pasutto, Bardakjian, Wilson, Watson et al., None, Clin Genet
Palczewski, Chemistry and biology of vision, J Biol Chem, doi:10.1074/jbc.R111.301150
Pasutto, Sticht, Hammersen, Gillessen-Kaesbach, Fitzpatrick et al., Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation, American Journal of Human Genetics, doi:10.1086/512203
Ruiz, Mark, Jacobs, Klopfenstein, Hu et al., None, Invest Ophthalmol Vis Sci
Tanoury, Piskunov, Egly, Vitamin A and retinoid signaling: Genomic and nongenomic effects, J Lipid Res, doi:10.1194/jlr.R030833
Tepasse, Vollenberg, Fobker, Kabar, Schmidt et al., Vitamin A Plasma Levels in COVID-19 Patients: A Prospective Multicenter Study and Hypothesis, Nutrients, doi:10.3390/nu13072173
West, Jr Extent of vitamin A de ciency among preschool children and women of reproductive age, J Nutr
{ 'institution': [{'name': 'medRxiv'}], 'indexed': {'date-parts': [[2022, 3, 9]], 'date-time': '2022-03-09T16:40:32Z', 'timestamp': 1646844032037}, 'posted': {'date-parts': [[2022, 3, 8]]}, 'group-title': 'Respiratory Medicine', 'reference-count': 0, 'publisher': 'Cold Spring Harbor Laboratory', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'short-container-title': [], 'accepted': {'date-parts': [[2022, 3, 8]]}, 'abstract': '<jats:p>The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 ' '(SARS-CoV-2) has infected over 100 million people causing over 2.4 million deaths over the ' 'world, and it is still expanding. Given the urgency of the COVID-19 pandemic, the clinical ' 'investigation of approved drugs is a promising alternative to find a timely effective ' 'treatment. In this randomized trial, we investigated the activity of both oral and ' 'aerosolized 13 cis retinoic acid in the treatment of SARS-COV-2 added to standard of care ' 'treatment in patients with COVID-19 versus standard of care treatment alone. This was a ' 'randomized controlled trial conducted at Kafrelsheikh Universitys Quarantine Hospitals, ' 'Egypt. After obtaining informed consent, forty patients with a confirmed diagnosis of ' 'COVID-19 were enrolled in the study. They were randomly assigned to one of two groups: Group ' 'I; 20 patients received aerosolized and oral 13 cis retinoic acid plus standard of care ' 'treatment (13 cis RA group) and Group II; 20 patients received only standard care treatment ' 'as a control group. The two groups were age and gender matched. There was no statistically ' 'significant difference between them in any of the baseline characteristics or laboratory ' 'parameters. The results showed that there was a high significant difference between the two ' 'groups regarding intensive care unit (ICU) admission, mortality and improvement ' '(P&lt;0.05). Only 10.52 % of patients in the 13 cis retinoic acid group needed ICU ' 'admission compared to 28.57 % in the control arm. There was no mortality in the 13 cis ' 'retinoic acid group, whereas about 14.35% were died in the group II. All patients who ' 'received 13 cis retinoic acid noticed a high improvement (P&lt;0.001), and the mean value for ' 'clinical improvement was 16 days. There was no significant difference regarding the ' 'laboratory parameters before and after 14 days of treatment in the group of patients received ' 'the standard of care treatment (P=0.66). Univariate logistic regression analysis showed ' 'overall mortality was significantly related to the patients age, serum ferritin, C-reactive ' 'protein, oxygen saturation, the presence of diabetes mellitus, obesity, and abdominal pain. ' 'We conclude that 13 cis retinoic acid is a promising drug in the treatment of patients ' 'with COVID-19 infection, when added to the standard of care treatment.</jats:p>', 'DOI': '10.1101/2022.03.05.22271959', 'type': 'posted-content', 'created': {'date-parts': [[2022, 3, 9]], 'date-time': '2022-03-09T01:40:54Z', 'timestamp': 1646790054000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': ['13 cis retinoic acid improved the outcomes of COVID-19 patients. A randomized clinical trial'], 'prefix': '10.1101', 'author': [ {'given': 'Mahmoud R', 'family': 'Elkazzaz', 'sequence': 'first', 'affiliation': []}, { 'given': 'Yousry', 'family': 'Esam-Eldin Abo-Amer', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-3477-236X', 'authenticated-orcid': False, 'given': 'Amr', 'family': 'Ahmed', 'sequence': 'additional', 'affiliation': []}, {'given': 'Tamer', 'family': 'Hayadar', 'sequence': 'additional', 'affiliation': []}], 'member': '246', 'container-title': [], 'original-title': [], 'link': [ { 'URL': 'https://syndication.highwire.org/content/doi/10.1101/2022.03.05.22271959', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 3, 9]], 'date-time': '2022-03-09T01:40:54Z', 'timestamp': 1646790054000}, 'score': 1, 'resource': {'primary': {'URL': 'http://medrxiv.org/lookup/doi/10.1101/2022.03.05.22271959'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 3, 8]]}, 'references-count': 0, 'URL': 'http://dx.doi.org/10.1101/2022.03.05.22271959', 'relation': {}, 'published': {'date-parts': [[2022, 3, 8]]}, 'subtype': 'preprint'}
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop   
Submit