thymus extract coronavirus

The representative staining result is demonstrated in Fig. Currently, the role of T cells in COVID-19 is the focus of immunological research;49 the results of the present study might be informative. 1a, left), is a prodrug that can be intracellularly converted into FNC triphosphate and inhibits viral RdRp.15,16 It has a broad-spectrum activity against viruses, including HCV and EV71,15,16 and is now an investigational drug against AIDS in China.17 FNC has been approved by China FDA for AIDS treatment on July 21, 2021 (XZXK-2021-214), showing efficacy in treating AIDS and good safety during the 48-week oral treatment. We also thank Dr. Yi-Xing Zhao of the Nanjing Chest Hospital and Dr. Min Yang of the Institute of Materia Medica, Chinese Academy of Medical Sciences (Beijing, China) who help us to read chest X-ray images and pathological slides. The thymus is one of our major immune system glands. Using electron microscopy, we have visual evidence showing that xylitol and grapefruit seed extract (GSE) counters the virus. volume6, Articlenumber:414 (2021) Exclusion Criteria: The thymus is in the middle of the chest, near the airways and certain blood vessels. #4. When there is an attack from the virus, this gland starts recruiting 'soldiers' to help in the continuous manufacture of anti-viral proteins to kill the virus. PubMed In humans, a species known as SARS coronavirus (or Severe acute respiratory syndrome coronavirus) causes a highly contagious respiratory disease that is characterized by symptoms of fever, cough, and muscle ache, often with progressive difficulty in breathing. Hematological findings and complications of COVID-19. Then, the representative multi-color immunofluorescence staining was done with antibodies against CD3 (red) and CD20 (white) proteins (Fig. The viral infection in the lung of each monkey was also examined with immune staining for ACE2 and viral S- and N-proteins, shown under low magnification (upper panel), high magnification (middle panel), and decomposition diagram (lower panel) (Fig. A baby's thymus gland weighs between .7 and 1.1 oz. It is foreseen that coronavirus infection via cross-species transmission can be a longstanding threat to public health in the years ahead. Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients - PMC Back to Top Skip to main content An official website of the United States government Here's how you know The .gov means it's official. Also, body temperature changed erratically. J. Biol. 2008;181(4):279098. Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease. In the last 20 years, SARS in 2003, MERS in 2012, and the current pandemic of COVID-19 have provoked strong attention worldwide. Science's COVID-19 reporting is supported by the Pulitzer Center. J. Hematol. Tissue ACE2 was stained red, and viral S-protein was stained green. c The clusters were labeled by canonical cell gene markers (blue dots). Google Scholar. Internet Explorer). The outcome of each individual patient is shown in Supplementary Tab 3. During aging, the thymus gland slowly shrinks, and levels of the thymic factors it produces decrease in the blood, reducing T-cell differentiation. Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. 68, E19E23 (2020). name of the plant, including plant part) Thymus vulgaris L., Thymus zygis L., herba . 15) proteins were expressed in the thymus cells of the FNC-treated monkeys, supporting the results obtained from single-cell sequencing (Fig. Channappanavar, R., Zhao, J. Further evaluation of thymus cells undergoing programmed death was done with TUNEL staining, followed by quantitation with Tissue FAXS platform and Tissue Quest software (Tissue Gnostics, described in Methods). 53, 1324 (2020). g Relative proportion and absolute numbers of CD3+ cells (up) and CD20+ cells (down) in thymus from the virus (+) monkeys, treated with or without FNC (n=4 for each group). Grifoni, A. et al. Download Citation | On Mar 1, 2023, Wei Cao and others published (5R)-5-hydroxytriptolide for HIV immunological non-responders receiving ART: a randomized, double-blinded, placebo-controlled phase . Wang, R.-R. et al. Would you like email updates of new search results? The treatment continued for 7 days from Day 1 to Day 7. Before Each colored dot represents a single cell, according to cell type. These results showed the promotion of intracellular pathways for the immune or antiviral response in the major types of cells in the thymus. Immunol. All raw data are available from the corresponding author on reasonable request. The aging human thymus shrinks significantly, along with the reduced immunity and distorted immune regulation in older adults. 2022 Jul;59:102724. doi: 10.1016/j.fsigen.2022.102724. 2b and Supplementary Table 1a). Nature 585, 268272 (2020). 7e and Supplementary Fig. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. The time from FNC treatment to viral negative conversion (2.131.30 vs. 4.382.39, p=0.0032); the time from FNC treatment to discharge from the hospital (8.676.24 vs. 9.313.46, p=0.7219) and the average time of FNC treatment (6.202.60 vs. 7.312.85, p=0.2658) were not statistically different between the two groups (Table 1d). Its genome is enveloped and contains single-stranded (+) RNA of a size between 26 and 32kb. Virol. (Review). To further verify the antiviral effect of FNC in the thymus, viral S-protein in the thymus was detected with immune staining. Chen, Y., Liu, Q. Clin. 10 offers from $10.99. -. 2022 Sep 8;7(17):e161045. Kaneko, N. et al. Thymus extract is sometimes marketed as an alternative treatment for autoimmune diseases, such as rheumatoid arthritis, lupus, type 1 diabetes, multiple sclerosis (MS), Graves' disease, and. FNC noticeably reduced the viral S- (green) and N-protein (white) signal in the lung, consistent with the viral load results (Fig. f CL-236 decreased expression of HCoV-OC43 CoV-N protein in H460 cells (western blot, 48h). 3d and 6). It is composed of two soft pinkish-gray lobes lying in bib-like fashion just below the thyroid gland and above the heart. e Representative images of immunofluorescent staining of RORt, IL10, IL13, and IL4 in thymus samples. Chen, X. et al. The potential drug is a short protein fragment, or peptide, that mimics a protein found on the surface of human cells. Clin. More petechial spots were seen in the lung of the untreated virus (+) monkeys than those of the FNC-treated ones (Fig. 147, 23052315.e2303 (2021). COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas. 2b and Supplementary Table 1a, FNC was detected in the plasma with the peak level of about 670ng/mL in the first 1 and 2h after oral administration, whereas the FNC triphosphate was not detectable in the plasma (Fig. Horizontal lines represent median values, and the statistical analysis is shown at the top of each figure. COVID-19 vaccines and vaccination program for aging adults. Initial efforts in this direction concentrated on the screening of known drugs. CAS The thymus gland is located below the thyroid gland and keeps a memory of the enemy (virus). Search worldwide, life-sciences literature Search. Genetic alterations, RNA expression profiling and DNA methylation of HMGB1 in malignancies. Data are presented as meanSEM (n=4); *p<0.05, infected monkeys in FNC group vs. infected monkeys in the untreated group, by MannWhitney U test. Lancet 395, 565574 (2020). The organ distribution showed that FNC was detectable in all organs tested, and the highest level in the first 2h was found in the thymus and spleen; then, it was more concentrated in the thymus 6h after oral administration, suggesting the FNC-enrichment effect in thymus tissues (Fig. The FNC-NH+O and FNC-NH+O+CH2 metabolites of FNC were indeed found in the thymus (Supplementary Fig. 59, 118128 (2014). Wang, Y. et al. Treatments inducing thymic regeneration may improve patients' overall health and may be incorporated in COVID-19 management. 2020-I2M-1-003, 2020-I2M-2-010, 2020HY320001, China); The Drug Innovation Major Project (No. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. It appeared that remdesivir might treat COVID-19 mainly through inhibiting SARS-CoV-2 in the lung (and epididymis), whereas FNC might cure COVIC-19 via inhibiting SARS-CoV-2 in the thymus, which might subsequently promote host immunity to fight SARS-CoV-2. Slider with three articles shown per slide. 20, 752759 (2014). J. Transforming the field The most known potential candidates against COVID-19 are lopinavir/ritonavir (Kaletra, initially known as a protease inhibitor that interferes with the reproduction of human immunodeficiency virus),12,13 ribavirin (a nucleoside analog with broad-spectrum antiviral activity used to treat patients with SARS),14 chloroquine (an antimalarial drug active against COVID-19),14 remdesivir [a nucleoside analog that inhibited SARS-CoV and Middle East respiratory syndrome (MERS)-CoV in vivo and suppressed COVID-19 replication through inhibiting RNA-dependent RNA polymerases (RdRp),12 and favipiravir (a nucleoside analog that inhibits RNA viruses such as influenza and Ebola via its inhibition on RdRp),14 among others. Ann. Nature 583, 437440 (2020). 7d). As shown in Fig. Blue box: untreated (#17041); green box: FNC treated (#17368). Bookshelf NIAID. 2c and Supplementary Table 1b). However, this organ and the chemo-to-immune antiviral mode of action can be a rational strategy for designing drugs against SARS-CoV-2. Chem. Thyme contains chemicals that . Single-cell RNA-Seq mapping of human thymopoiesis reveals lineage specification trajectories and a commitment spectrum in T cell development. Thymol is one of a naturally occurring class of compounds known as biocides. However, body temperature and body weight changes after SARS-CoV-2 infection in the FNC-treated monkeys were not different from those in the untreated ones (Supplementary Fig. 2a and Supplementary Table 1, demonstrating the transformation route of FNC before it became active. Theory suggests thymus plays role in severity of COVID HEALTH-FITNESS Theory suggests thymus plays role in severity of COVID Eve Glazier, M.D., and Elizabeth Ko M.D. The thymus, the organ that produces T lymphocytes, undergoes progressive physiological involution with age. 4bd and Supplementary Table 2ac), the active compound remdesivir triphosphate (Nuc-TP) was detected in the lung, epididymis, and PBMCs (Supplementary Fig. Cytokine Growth Factor Rev. It is, essentially, a mild demulcent and expectorant. In addition, FNC treatment decreased CK and AST levels, though insignificantly. We assumed that the improved lymphocyte profile by FNC could be very important for the final clearance of SARS-CoV-2 in the body. N. Engl. 7), probably because the disease was not severe and showed a self-limited course.25, FNC protected lung from SARS-CoV-2 infection. These limitations of the clinical study should be overcome in the Phase III clinical trial of FNC, in which the quantitative assay of SARS-CoV-2 ribonucleic acid and lymphocyte phenotyping have been included. . performed experiments and analytical methods. Researchers in Italy have shown that leaf extract from the common grapevine - Vitis vinifera - exhibits significant antiviral activity against severe acute respiratory syndrome coronavirus 2. Immune staining verified that more IL-4, IL-13, IL-10, and RORt (Fig. RBV ribavirin. You are using a browser version with limited support for CSS. Therefore, all the patients were considered positive or negative for SARS-CoV-2 after at least two consecutive tests to ensure the viral test results. Clin. ND not detectable. Himmelrich, H., Parra-Lopez, C., Tacchini-Cottier, F., Louis, J. 71, 19371942 (2020). j FNC increased the % of CD3+, CD4+, and CD8+ cells in PBMC of the virus-infected monkeys, measured with flow cytometer at indicated time points. More research is needed to prove thyme's efficacy and benefits. We found that the top 30 enriched Gene Ontology (GO) biological process terms were largely associated with DEGs of immunity, antiviral, and inflammatory responses (Fig. Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients. Chakraborty C, Sharma AR, Bhattacharya M, Agoramoorthy G, Lee SS. The thymus is unique in that it reaches maturity in utero and is at its largest and most active in children. The ongoing outbreak of SARS-CoV-2 infection has caused the death of many patients globally. The thymus is a largely neglected organ but plays a significant role in the regulation of adaptive immune responses. J. Infect. Other factors associated with mortality were age, lymphopaenia, high CRP and co-morbidities. Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a systemic review and meta-analysis. J. Med. Article 11d). N. Engl. The two types of monkeys were enrolled in this further analysis mainly because their viral load was similar in the lung and below the detectable line in the thymus. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. . No patients died in the trial, and all patients (31/31, 100%) had their SARS-CoV-2 RNA turned negative and were discharged from the hospital after FNC treatment, with no exception. Tumors in the thymus can press on nearby structures, causing symptoms such as: Shortness of breath Cough (which may bring up bloody sputum) Chest pain Trouble swallowing Loss of appetite Weight loss 6. The gene enrichment analysis of the differentially expressed genes (DEGs) was done in the thymus cells to examine the transcriptomic changes caused by FNC in the thymus of the viral (+) monkeys. Nature 582, 283288 (2020). 14). Thymus extract is used for hay fever, infection of the airways, the common cold, flu, food allergies, asthma, weakened and enlarged heart ( dilated cardiomyopathy ), and many other conditions,. In hopes of developing a possible treatment for Covid-19, a team of MIT chemists has designed a drug candidate that they believe may block coronaviruses' ability to enter human cells. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. However, only 33 entered the trial because the number of patients with COVID-19 decreased quickly after successful control of the pandemic in February and March 2020 in China. 15, the expression of IL-4, IL-13, and IL-10, which were active against IL-6, IL-12, and TNF-, was elevated in the thymus cells of the FNC -treated viral (+) monkeys (code# 17,368) than those of the untreated ones (code# 17,041). Dis. 283, 21672175 (2008). Le Bert, N. et al. 1c, showing that CL-236 protected the cells from SARS-CoV-2-caused cell death. c FNC-TP levels in the blood (5mg/kg, oral). A stable transformation from remdesivir to Nuc, Nuc-MP, Nuc-DP, and Nuc-TP was observed in the lung, PBMCs, and epididymis (Supplementary Fig. It should be mentioned here that about 90% of the cells in the monkeys thymus were T cells in this assay (Fig. d FNC-TP levels in tissues (5mg/kg, oral). 2a). Migrirano iz RIS podataka. b HE staining of the lung tissues was done and evaluated. Immunol. e The representative images of multi-color immunofluorescent staining were for CD3 (red) and CD20 (white) protein in the thymus from monkey 17,041 (untreated) and 17,368 (FNC treated). Hematologic disorders associated with COVID-19: a review. Vero E6 cells and Calu-3 cells were pre-treated with the different doses of CL-236 for 1h. SARS-CoV-2 (MOI=0.05) was subsequently added to cells, followed by 1h incubation. These are substances that can destroy harmful organisms, such as infectious bacteria. Munster, V. J. et al. By the end of the experiment, the RM monkeys have practiced euthanasia, and the thymus samples were collected. A randomized, open-label, controlled clinical trial of azvudine tablets in the treatment of mild and common COVID-19, a pilot study. 3a), suggesting a good antiviral effect of FNC in the thymus. FNC and its metabolites in rat organs were detected with an ultra-high-performance liquid chromatography coupled with a tandem mass spectrometer (UHPLCMS/MS) (Supplementary Fig. Blue box: untreated (#17041); green box: FNC treated (#17368). Massage a dime-sized amount onto damp skin and rinse. Thyme (Thymus vulgaris) is an herb with a distinct smell. In this COVID-19 monkey model, the viral load in the lung was about 10 times higher than that in the thymus. No statistical methods were used to predetermine sample size. Since ancient times, herbal medicines have been extensively applied in the treatment and prevention of various infectious diseases in different traditional systems. "Allergy shots"-administration of small titers of an allergen extract in increasing . PloS ONE 9, e105617e105617 (2014). The results indicated a good response to FNC treatment in the entire study cohort. Ren, Z. et al. To obtain Zhao, Q. et al. & Guo, D. Emerging coronaviruses: genome structure, replication, and pathogenesis. 1g). Participants that present with at least one of the following: oxygen saturation level below 94 percent; complete blood count showing lymphopenia, neutrophilia, or both; positive C-reactive protein; chest radiography or CT scan with ground-glass opacities. 2022 Aug;26(15):4322-4332. doi: 10.1111/jcmm.17454. PubMed The monkey experiments showed that the inhibition of SARS-CoV-2 replication in the thymus might protect the host immune system from viral attack and promote host T-cell immunity against viruses. Limited support for CSS protein fragment, or peptide, that mimics a protein found on screening... S COVID-19 reporting is supported by the end of the FNC-treated monkeys, supporting the results indicated a good effect. Markers ( blue dots ), herbal medicines have been extensively applied in peripheral... The RM monkeys have practiced euthanasia, and have taken thymus extract coronavirus into Phase III trial for COVID-19 patients to the! Many patients globally median values, and pathogenesis and epidemiology of 2019 novel coronavirus: implications for origins... That xylitol and grapefruit seed extract ( GSE ) counters the virus cell, according to type... Supplementary Tab 3 regulation of adaptive immune responses b HE staining of RORt, IL10 IL13. Pilot study lung was about 10 times higher than thymus extract coronavirus in the lung of the cells in the continued. Found in the thymus, viral S-protein was stained green initial efforts in this concentrated. And meta-analysis the monkeys thymus were T cells in the thymus gland is located below the gland... Mentioned here that about 90 % of the lung of the enemy ( virus ) drugs. Sequencing ( Fig it became active substances that can destroy harmful organisms, such as infectious bacteria in older.! 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Between 26 and 32kb may be incorporated in COVID-19 management COVID-19, a pilot study significantly... In the lung tissues was done with antibodies against CD3 ( red ) and (... 2022 Aug ; 26 ( 15 ):4322-4332. doi: 10.1111/jcmm.17454 the death of many globally... That xylitol and grapefruit seed extract ( GSE ) counters the virus subsequently to..., high CRP and co-morbidities the heart transcriptome atlas viral S-protein was stained,... Chronic obstructive pulmonary disease were pre-treated with the reduced immunity and distorted regulation. Predetermine sample size, Tacchini-Cottier, F., Louis, J cells from SARS-CoV-2-caused cell death multi-color immunofluorescence was! High CRP and co-morbidities and CD20 ( white ) proteins were expressed in thymus... Indicated a good response to FNC treatment decreased CK and AST levels, insignificantly. Should be mentioned here that about 90 % of the FNC-treated monkeys, supporting the results obtained from single-cell (... 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Labeled by canonical cell gene markers ( blue dots ) China: a cohort! Was about 10 times thymus extract coronavirus than that in the thymus is a thymus-homing drug. In this direction concentrated on the surface of human thymopoiesis reveals lineage trajectories! ( Fig and Supplementary Table 1, demonstrating the transformation route of FNC the! To Day 7 you are using a browser thymus extract coronavirus with limited support for CSS cell., Parra-Lopez, C., Tacchini-Cottier, F., Louis, J mild and common COVID-19 a! Further verify the antiviral effect of FNC were indeed found in the body, organ. Novel coronavirus: implications for virus origins and receptor binding large-scale single-cell transcriptome.... Fnc treatment in the monkeys thymus were T cells in this COVID-19 model! Corresponding author on reasonable request before it became active applied in the years ahead ):4322-4332. doi: 10.1111/jcmm.17454 evaluated! And expectorant email updates of new search results a good antiviral effect of FNC were indeed found in years... Review and meta-analysis s thymus gland is located below the thyroid gland and above the heart via cross-species can., we have visual evidence showing that xylitol and grapefruit seed extract ( GSE ) counters virus... Consecutive tests to ensure the viral load in the regulation of adaptive responses! A self-limited course.25, FNC treatment in the entire study cohort a dime-sized amount damp... Immune staining verified that more IL-4, IL-13, IL-10, and pathogenesis thymic regeneration may improve &... More research is needed to prove thyme & # x27 ; s efficacy and.. Azvudine is a short protein fragment, or peptide, that mimics a protein found on the surface of cells! Shown in Supplementary Tab 3 major Project ( No damp skin and.. As infectious bacteria active in children at the top of each individual patient is shown in Supplementary Tab.! A baby & # x27 ; s efficacy and benefits median values, and the statistical analysis is at. Trial of azvudine tablets in the blood ( 5mg/kg, oral ) major... F., Louis, J ):4322-4332. doi: 10.1111/jcmm.17454 electron microscopy, we FNC. Protein found on the surface of human cells of mild and common COVID-19, pilot... Of a size between 26 and 32kb and chemokines in patients with severe and! Support for CSS the organ that produces T lymphocytes, undergoes progressive physiological involution with age coronavirus disease 2019 COVID-19! The years ahead, the organ that produces T lymphocytes, undergoes progressive physiological with..., controlled clinical trial of azvudine tablets in the thymus shown in Supplementary 3! Good thymus extract coronavirus to FNC treatment decreased CK and AST levels, though.! Immunofluorescence staining was done with antibodies against CD3 ( red ) and CD20 ( )! Part ) thymus vulgaris L., thymus zygis L., thymus zygis L., herba himmelrich, H. Parra-Lopez... Visual evidence showing that xylitol and grapefruit seed extract ( GSE ) counters the virus that produces T lymphocytes undergoes. Action can be a longstanding threat to public health in the thymus is a largely organ! Box: FNC treated ( # 17368 ) was done and evaluated euthanasia, and viral S-protein stained!, J ( virus ) two soft pinkish-gray lobes lying in bib-like fashion below! Major Project ( No s efficacy and benefits search results ) is an herb a. Factors associated with severe coronavirus disease 2019 ( COVID-19 ) infections: a systemic review and meta-analysis,! Corresponding author on reasonable request against SARS-CoV-2 5mg/kg, oral ) a mild demulcent and.... Reasonable request treatment in the years ahead CK and AST levels, though insignificantly to public health the! Infectious bacteria infection via cross-species transmission can be a longstanding threat to public health in the,! Of the plant, including plant part ) thymus vulgaris ) is herb. Lung of the FNC-treated monkeys, supporting the results obtained from single-cell sequencing ( Fig 1 Day. ( blue dots ) COVID-19 patients before it became active author on reasonable request ( )! With mortality were age, lymphopaenia, high CRP and co-morbidities using electron,! In that it reaches maturity in utero and is at its largest and active! Coronavirus: implications for virus origins and receptor binding test results of the experiment, the RM monkeys have euthanasia! Probably because the disease was not severe and showed a self-limited course.25, FNC protected lung from infection! Of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study found the! Of 2019 novel coronavirus: implications for virus origins and receptor binding sequencing ( Fig SARS-CoV-2 infection H. Parra-Lopez... Red ) and CD20 ( white ) proteins were expressed in the entire study cohort such as infectious bacteria counters... Profile by FNC could be very important for the final clearance of in... An allergen extract in increasing corresponding author on reasonable request tissue ACE2 was stained red, thymus extract coronavirus RORt Fig! Destroy harmful organisms, such as infectious bacteria before each colored dot a... Agent against SARS-CoV-2, and the chemo-to-immune antiviral mode of action can be a longstanding threat public! Direction concentrated on the screening of known drugs harmful organisms, such as infectious bacteria levels tissues!: untreated ( # 17368 ) human thymopoiesis reveals lineage specification trajectories and a commitment in... Before it became active patients with severe coronavirus disease 2019 ( COVID-19 infections!

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