Asian Journal of Biomedical and Pharmaceutical Sciences

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Review Article - Asian Journal of Biomedical and Pharmaceutical Sciences (2022) Volume 12, Issue 92

A review on synergistic action of vitamin D glutamine and oncothread immuno modulators in interferon signalling and COVID-19.

Muzahid K Sheikh*

Department of Physiotherapy, Datta Meghe College of Physiotherapy Nagpur, Maharashtra University of Health Sciences, Nagpur, India

Corresponding Author:
Muzahid K Sheikh
Department of Physiotherapy
Datta Meghe College of Physiotherapy Nagpur
Maharashtra University of Health Sciences, Nagpur, India

Received: 18-July-2022, Manuscript No. AABPS-22-67778; Editor assigned: 21-July-2022, PreQC No. AABPS-22-67778(PQ); Reviewed: 04-Aug-2022, QC No. AABPS-22-67778; Revised: 08-Aug-2022, Manuscript No. AABPS-22-67778(R); Published: 15-Aug-2022, DOI:10.35841/2249-622X.92.136

Citation: Sheikh MK. A review on synergistic action of vitamin D glutamine and oncothread immuno modulators in interferon signalling and COVID-19. Asian J Biomed Pharmaceut Sci. 2022;12(92):136


Novel Coronavirus disorder 2019 (COVID-19), is due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been discovered in the month of December 2019 in Wuhan, China, and has made headway hastily to cover diverse countries while the investigation for competent pharmacotherapy goes on. Coronaviruses, inclusive of SARS-CoV-19, are acknowledged to conceal Associate in Nursing stand back from the host organism' antiviral responses mediate with the help of victimization antiviral (IFN), a own circle of relatives of cytokines which performs an essential position in antiviral resistance concerning body’s defense mechanism and has been utilized curatively for persisted virus sicknesses upon opportunity hand, OncoTherad, a stable and potent adoptive immunotherapy with inside the therapy of nonmuscle invasive bladder cancer (NMIBC), will boom IFN signaling and come to be validated remain an encouraging restoration method for COVID-19 in an inquiry that represented the short recuperation of a 78year old vintage NMIBC affected individual with comorbidities. This consider targets to find out the viable synergistic motion of OncoTherad with vitamins like, zinc and glutamine, vitamin-d those microelement play an vital position in reinforcement the body’s defenses, and fight against pathogens by different mechanisms such as vitamin d is antiinflammatory and also helps in prevention of tissue injury by inhibiting cytokines strom, zinc is very necessary for development and proper functioning of immune cells as well as it prevent viral replication and glutamine act as a reservoir of fuel for immune cells and also exhibit antioxidant properties thus adequate nutritional support from micronutrients can have a positive impact on the outcome of COVID19. Have been validated to facilitate immune responses mediated with the aid of using IFN signaling, in addition to the ability of this mixture in regulating immune characteristic with inside the remedy of COVID-19. The emphasis of this article is briefly on the relationship between micronutrient such as zinc, vitamin d, glutamine, on covid19 with synergistic presence of interferon’s and Oncothread in the treatment regime.


COVID-19, SARS-CoV-2, Interferon, Immunity, Zinc, Glutamine, Vitamin D, Oncotherad.


Coronavirus named ‘COVID-19’ or ‘2019 novel coronavirus’ via way of means of the World Health Organization (WHO) is going for walks the display for the continued outbreak of pneumonia which were given opened up at the start of December 2019 close to in Wuhan City, Hubei Province, China [1].

A near communion among the corona virus and the body’s defense machine of person consequences in variegated miscellaneous medical manifestations of the SARS-CoV-2 sickness. While antibody production after antigen exposure either from pathogen or vaccination are considered necessary against corona virus, the cells of natural immune system, including macrophages, might also additionally lead , to the sickness development in a few cases. Macrophages have proven a superb manufacturing of IL-6, advocating they will make contributions to the immoderate infection in COVID-19 sickness. Macrophage Activation Syndrome might also additionally in addition elucidate the excessive serum stages of CRP, which might be usually missing in viral disease. In adaptive immunological reaction, it is indicated that cytotoxic CD8+ T cells display operative expenditure patterns, which includes the expression of NKG2A, PD-1, and TIM-3. As corona virus limits pathogen presentation with the aid of using negative regulating MHC elegance I and II molecules with, consequently obstructs the T cell mediated antibody reaction, B cell mediated antibody reaction additionally act as widespread catalyst. Particularly IgA reaction seems to be higher and greater enduring over IgM reaction. In addition, IgM and IgG antibodies exhibit likewise kinetics in corona virus disease [2].

Several vitamins possess the quality of harmonizing the natural immune system along the acquired immune system, and act as a critical component against viral disease. The discovery regarding dependable collaborative moves amongst vitamins, in addition to among vitamins and drugs, might also additionally supply the improvement of complicated formulations that capabilities incredibly from the man or woman components. In this context, positive atypical vitamins, specifically zinc, vitamin D and glutamine had being scrutinized. These vitamins are referred to as ability adjuvants in the treatment and prevention of viral disease [3].

Vitamin D

Vitamin D is one of the fat soluble nutrition which performs diverse crucial functions in your body, Sunlight is the key source of VITAMIN D, human body utilize ultraviolet rays of sun to convert cholesterol into vitamin D [4].

IT is a key nutrient your body demands to invigorate and strength your bones ,furthermore it is require for the appropriate and effective Functioning of your immune system — that is body’s first line of defence towards contamination and disease [5]. Vitamin D deficiency is also been mentioned to hike a process named the “cytokine storm” [6] these cytokines results in intense tissue injury and promote disease intensity as well as severity, A cytokine storm denotes to the unrestrained exposure of pro-inflammatory cytokines that occur as result of infection, This imbalance in the level of cytokines cause massive tissue injury and progression of disease and severity [7].

These cytokine storm also occurs in COVID 19 infection if left untreated and worsen the condition of the patient by immuno pathogenic damage that leads to ARDS (acute respiratory distress syndrome) also tissue degeneration, multiple organ failure and eventually death. Many research have been published and postulated that vitamin D supplementation are able to minimize complexity and hindrance which is resulted due to cytokine storms and uncontrolled inflammation in patients of COVID-19 [8]. Thus, it's far important to encompass diet d in COVID-19 treatment, after tested its level.

Zinc (ZN)

Zinc is a micronutrient which is an essential element needed by body in small quantity, it is necessary since many constitutional activities, especially growth and proper functioning of immune cells like t-cells, white blood cells specially neutrophils, immune gadget relies upon at the enough accessibility of this micronutrient. in past few a long time, lots of researches have done to persuade the prognosis of diverse sicknesses by means of supplementing zinc, together with diarrhoea, continual hepatitis C, Shigellosis, leprosy, tuberculosis, pneumonia, acute decrease respiration infections as well as recently for COVID-19 also [9] the participation zinc (Zn) in heterogeneously influencing direct and indirect antiviral properties, is also well established which can be obtrusive through distinctive mechanisms. Regime of zinc adjuncts have a capability to strengthen resistance against viral infection, each innate in addition to humoral, and to regenerate exhausted immune cellular characteristic or to decorate common immune mobile property, particularly in immuno deficient or immuno compromise sufferers. Zinc can perform distinctly and is very effective when administered in combination with the conventional remedies against virus; Zinc can additionally secure or balance the cellular surface that prevents the access of virus into the cellular. Except this, it became revealed that Zn can also suppress viral replication through alteration in processing of proteolysis replications poly proteins by its mis folding [10], further Zn can impact numerous capabilities of transduction by monocyte signaling further more by launching cytokine induced seasoned-antiinflammatory response, and interrupt the bond of white blood cells feature-related antigen1 to Intercellular adhesion molecule1, therefore control inflammation. This could explain the reduction in infection skilled by means of humans taking zinc gluconate/glycine (ZGG) capsules to deal with CHD. Rhinitis caused by allergy and Chronic cough has numerous general signs and symptoms, and zinc, gluconate / glycine additionally reduces the signs and symptoms of allergic rhinitis (RA). Focal stimulation, multiplied ICAM1 expression, and leukocyte recruitment to lesions of epithelium are usual component. Zn ions perhaps are a critical element due to the fact they could block the coupling of HRV and LFA1 with ICAM1 [11].

Thus including zinc in COVID-19 treatment regimens is an effective and wise measure as it helps in decreasing severity as well as mortality.


When cells are diseased through a virulent disease, viral pathogen-related molecular patterns (PAMPs) could be outstanding via diverse intracellular TLR reputation receptors (PRRs), such as TLRs. Like TLR 2, TLR 3, TLR 4, TLR 7, TLR 8 and TLR 9 play huge element in identity of chromosomes (RNA and DNA) precise to the viral genome. Sure viruses are able to steer clear of from TLRs and can be preferred through a few other intracellular PRRs present with inside the cytosol. In spite of diverse sort of PRRs that may be induced, the antiviral immune reaction after the PAMPPRR interaction embody similar signaling pathways. Normal, the popularity of viral antigen is accompanying the release of several inflammatory cytokines, particularly IFNs, that have a massive antiviral and anti-proliferative movement [12] specifically type 1 interferon.

Interferons (IFNIs) was primary found 60 years before a classic study with linden man and Isaacs that found IFNIs have antiviral activity in great detail of the body's first line of defense, human interferons1 include thirteen Comparable IFNα with eighty percent lower homology and single IFN ω, κ, ? and β, with less homology (30-50%). Type I interferons (IFNI) are a separate member of cytokines family that combines to the type I interferon receptor and are made from the IFNAR1 and IFNAR2 transmembrane subunits. Receptors originate from an in vitro zone that combines IFNI, a transmembrane helix, and intracellular unstructured regions (ICD) which combine JAK and STAT [13] with respect to immunological factors, Interferon are capable in 3 predominant feature:

To spark off against viral country at inflamed region and also at surrounding tissue which help in prevention of viral disease?

Regulate body’s natural immune system, including presentation of pathogen and also have pathogen killing capabilities which limit the cause of inflammation.

Stimulating body’s antibody response mechanism in order to improve the affinity against antigen specifically T lymphocytic and B lymphocytic response [14].

Considering interferons as an energetic cell, their antigen presenting and monitoring efficiency is highly essential. IFNIs speak among cells towards pathogens and feature a crucial position with inside the body’s defence mechanism, consisting of stimulating macrophages and herbal killer (NK) cells Opposing augmenting and suppressive indicators are triggered with the aid of using host factors [15]. IFN-Is purpose flu-like signs, which can be determined in diverse diseases. These signs might also additionally have a position in alerting someone of his/her sickness that allows you to restrict ailment-unfold to different individuals. Corona virus infection has been proven in inhibiting interferon mechanism with inside the infected individual via more than one pathway. A restrained interferon reaction minimize presentation of antigen along with thus it also decreases the adaptive immunological response against virus. Corona virus infection enforces techniques to avoid the defence response with the aid of using antagonizing IFN-I brought on signaling pathways. This dampening technique is surprisingly related to the ailment severances and elevated death rate [16]. Across the deadly instances of Covid-19 infections, it is observed that the entry of inflammatory cells is increased. In a small version of Covid-19 infection, dis balance between inflammatory molecules and interferon had been proven for primary reason of deadly lung inflammation [17].


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OncoTherad compound made up of steel salts and phosphate in Nano metric form and is related to a glycosylation of protein with a size of 420-530 nm. This new therapy by nanomaterial encourages body’s defence system to eradicate malignant tumors and might be a favorable approach in opposition to corona virus infection. It is a new therapy via intravesical approach of immunizing along with antineoplastic qualities in favours of medical care of NMIBC. Though surgical transurethral resection is the essential remedy for NMIBC, which is observed by intravesical BCG immunotherapy to prevent tumor development and reduce recurrence. more precisely, the induction of the body’s defence system caused by OncoTherad by toll like receptor 2 and4 occurs via phosphorylation of hydroxylated amino acids like tyrosine, threonine and serine through compounds containing salts of phosphate, which leads to the actuation of stimulator of interferon genes ,along with subsequent enhance in the production of IFNα and IFN γ. The enhancement inside the generation of IFNs encourages the actuation of T lymphocytes, antigen presenting cells along with phagocytic cell, concluding to the prime efficacy of Onco therad inside the medical management of bladder, majority of malignant tumour whenever correlated to BCG. On experimenting on rodents and puppies it highlighted that it is capable of lower the appearance of receptor activator of nuclear element κ B (RANK) and receptor activator of nuclear element κ B ligand (RANKL) reaction and, consequently preventing the spread of cancer and neutralize its development.

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A case report was made to detect the action of this immunotherapy on a covid19 positive 78 year old patient with nmibc, the patient received Oncothread prior to hospitalization, it was observed that that symptoms improved after 6 days and on the 8th day there as significant improvement and the on 10th day the patient was discharged. It was observed that the patient showed progressive and rapid recovery with shorter time as compared to the previous study. In a Chinese language look at out of 100 sufferers 86 sufferers have been discharged after sixteen days of hospitalization with maximum of the person on 7th day showing radiologic deterioration and development on 14th day.

According the record file of immunological remedy along Oncothread, 33 molecules associated with the metabolic kingdom have been diagnosed with the aid of delafiori et al ate entrance and 39 on improving of the hospital circumstance and after the hospital stay. On thinking about patents having coexisting morbid conditions along with their age means that immunological therapy with Oncothread exhibit a protecting position on the affected person, stopping the development of disease to its maximum excessive level and encouraging rapid recuperation with no use of intensive care [18].


Glutamine is the principal amino alkanoic acid with inside the humans, which encompass sixty percentage of the general collection of unfastened amino alkanoic acids. The main synthetic sources of (levo) glutamide distributed in protoplasm are stratified muscle, fat storing tissue, and respiratory unit. (Levo) glutamide perform majority nitrogen transportation out of stratified muscle towards internal organ. (Levo) glutamide is serves as a number one gasoline for lots hastily dividing cells, such as RBCs, colonocytes, lymphocytes, and fibroblasts [19]. Glutamine performs a position in basilar stability vis the manufacturing of ammonium with inside the excretory, their oxidated shape NH2O affords the raw material for the production of pyrimidine’s and purines vital in manufacturing of genetic material. Likewise it is a pioneer of effective antioxidant that is glutathione which is endogenously manufactured. It belongs to the most investigated amino alkanoic on a couple of factors of scientific dietary care, such as situations inclusive of GIT diseases, observe of tumours, burned trauma , HIV/ AIDS, and persistent lesion control and COVID-19 [20]. Furthermore, (levo) glutamide has proved to be frequent as a reservoir of fuel for body’s defence mechanism, inclusive phagocytic cell and white blood cells, which might be required to supply unique immuno stimulatory results. Newly, (levo)glutamide and glutamate-derivative amino alkoanoicbio genesis was tested as an essential element to be necessary for the production collagen tissue in fibroblastic cell along with demarcation of myo fibroblastic cell inside respiratory system As formerly stated in several breathing viruses, corona virus is mentioned presently to intention the infected body, consisting of myofibroblastic, showingACE2 receptors and induction of ARDS, Nutritional dietary supplements along with L-Glutamine improve immunological device particularly through inhibition of inflammatory responses. Our outcomes propose including intestinal L-glutamine to the everyday nutrients with inside the onset duration of COVID-19 contamination can also additionally result in a discounted medical institution live and result in uncommon want for ICU.

This look at estimate the results of L-Glutamide usage on administrated duration, sizable medical attention, along with deaths due to corona virus sufferers at the side of decrease respiration tract involvement. On contrast sufferers provided with L-Glutamine confirmed shorter period of hospitalization and want for extensive care than people who did now no longer use L-Glutamine. This become the primary examine with inside the literature analyzing the consequences of immune dietary supplements along with L-glutamine brought to traditional contemporary remedies at the route of COVID-19 [21].


Along with the development of the SARS-CoV-2 outburst, there's a pressing want in recognition of techniques which could participate in a fight against corona virus infection. Onco therad with Immunotherapy has turned out to be a secure as well as a powerful with inside the remedy of Non muscle invasive bladder cancer via way of means of growing the signaling related to Interferons and cytokines which has a crucial ability with inside of stimulation of the body’s natural defence against any pathogen including virus [22]. Zinc, nutrition D and glutamine vitamins, and the OncoTherad immuno modulator act as activators of interferon manufacturing and, therefore, display big synergistic capability with inside the remedy of COVID-19, they're necessary against viral response, with emphasizing in the involvement of those vitamins which take part in interferon signaling, prompting an adjunctive and synergic healing capability with Onco therad to modulate the defence mechanism with inside the remedy of corona virus infection [23-25]. Hence, the capability useful function of those compounds at some stage in contamination via way of means of SARS-Cov-2 justifies the want for pre-medical and medical research that validates their mixture and standardizes the dosages that offer the best advantage to the patient.”


This evaluation examined the position of elements like zinc, vitamin C, also vitamin D in body’s defence system, as these micronutrients have the strongest grounds in favours of natural immunity boosting process. In this situation, the research cited above shows that zinc and vitamins C and D are significant elements of the body’s defence machine and exhibit synergic talents in numerous levels in immune system, including assuring the fundamentals of organ boundaries and properties of immune cells that built body’s immune systems. Thus, any inadequacy or shortage of these fundamental elements, which are found synergistically in adherent and tight-junction proteins, can lead to deterioration of upper mucosal lining, making them in all likelihood particularly vulnerable to invasion by compound pathogens. By corona virus. Universally, the scientific researches shows that adjunct therapy with nutrients zinc, vitamin D, along with vitamin C can reduce viral respiratory tract infection. For this reason, supplementation with such nutrients with respect toSARSCoV- 2outbreak can be described as an easily accessible, convenient, coffee fee diploma that can be helpful in meeting the growing need for vitamins in the event of contact with the virus and That initiation of immune responses similar to those that reduce the risk of excessive development and the outcome of this corona virus contamination.


  1. Hanaei S, Rezaei N. COVID-19: developing from an outbreak to a pandemic. Archives Med Res. 2020;51(6):582.
  2. Indexed at, Google Scholar, Cross Ref

  3. Paces J, Strizova Z, Daniel SM, et al. COVID-19 and the immune system. Physiol Res. 2020;69(3):379.
  4. Indexed at, Google Scholar, Cross Ref

  5. Read SA, Obeid S, Ahlenstiel C, et al. The role of zinc in antiviral immunity. Adv Nutrition. 2019;10(4):696-710.
  6. Indexed at, Google Scholar, Cross Ref

  7. Maghbooli Z, Sahraian MA, Ebrahimi M, et al. Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. PloS one. 2020;15(9):e0239799.
  8. Indexed at, Google Scholar, Cross Ref

  9. Bivona G, Agnello L, Ciaccio M. The immunological implication of the new vitamin D metabolism. Central Europ J Immunol. 2018;43(3):331-4.
  10. Indexed at, Google Scholar, Cross Ref

  11. Marik PE, Kory P, Varon J. Does vitamin D status impact mortality from SARS-CoV-2 infection?. Med Drug Discovery. 2020;6:100041.
  12. Indexed at, Google Scholar, Cross Ref

  13. Ye Q, Wang B, Mao J. The pathogenesis and treatment of theCytokine Storm'in COVID-19. J Infec. 2020;80(6):607-13.
  14. Indexed at, Google Scholar, Cross Ref

  15. Vasconcelos AR, Souza AC, Fávaro WJ. Vitamin D, zinc and glutamine: Synergistic action with OncoTherad immunomodulator in interferon signaling and COVID-19. Int J Mol Med. 2021;47(3):1-.
  16. Indexed at, Google Scholar, Cross Ref        

  17. Overbeck S, Rink L, Haase H. Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases. Archivum Immunol et Therapiae Experimentalis. 2008;56(1):15-30.
  18. Indexed at, Google Scholar, Cross Ref

  19. Kumar A, Kubota Y, Chernov M, et al. Potential role of zinc supplementation in prophylaxis and treatment of COVID-19. Med Hypotheses. 2020;144:109848.
  20. Indexed at, Google Scholar, Cross Ref

  21. Novick SG, Godfrey JC, Pollack RL, et al. Zinc-induced suppression of inflammation in the respiratory tract, caused by infection with human rhinovirus and other irritants. Med Hypotheses. 1997;49(4):347-57.
  22. Indexed at, Google Scholar, Cross Ref

  23. Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nut. 2015;7(6):4240-70.
  24. Indexed at, Google Scholar, Cross Ref

  25. Thomas C, Moraga I, Levin D, et al. Structural linkage between ligand discrimination and receptor activation by type I interferons. Cell. 2011;146(4):621-32.
  26. Indexed at, Google Scholar, Cross Ref

  27. Linossi EM, Nicholson SE. Kinase inhibition, competitive binding and proteasomal degradation: resolving the molecular function of the suppressor of cytokine signaling (SOCS) proteins. Immunol Rev. 2015;266(1):123-33.
  28. Indexed at, Google Scholar, Cross Ref

  29. Wilmes S, Beutel O, Li Z, et al. Receptor dimerization dynamics as a regulatory valve for plasticity of type I interferon signaling. J Cell Biol. 2015;209(4):579-93.
  30. Indexed at, Google Scholar, Cross Ref

  31. Dandekar AA, Perlman S. Immunopathogenesis of coronavirus infections: implications for SARS. Nat Rev immunol. 2005;5(12):917-27.
  32. Indexed at, Google Scholar, Cross Ref

  33. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. In Seminars Immunopathol. 2017;39(5):529-539.
  34. Indexed at, Google Scholar, Cross Ref

  35. Bergström J, Fürst P, Noree LO, et al. Intracellular free amino acid concentration in human muscle tissue. J Applied Physiol. 1974;36(6):693-7.
  36. Indexed at, Google Scholar, Cross Ref

  37. Savy GK. Glutamine supplementation: heal the gut, help the patient. J Infusion Nursing. 2002;25(1):65-9.
  38. Indexed at, Google Scholar, Cross Ref

  39. Cengiz M, Uysal BB, Ikitimur H, et al. Effect of oral l-Glutamine supplementation on Covid-19 treatment. Clin Nut Exp. 2020;33:24-31.
  40. Indexed at, Google Scholar, Cross Ref

  41. Gombart AF, Pierre A, Maggini S. A review of micronutrients and the immune system–working in harmony to reduce the risk of infection. Nut. 2020;12(1):236.
  42. Indexed at, Google Scholar, Cross Ref

  43. Souza AC, Vasconcelos AR, Prado PS, et al. Zinc, vitamin D and vitamin C: perspectives for COVID-19 with a focus on physical tissue barrier integrity. Frontiers in Nut. 2020:295.
  44. Indexed at, Google Scholar, Cross Ref

  45. Butola LK, Kute PK, Anjankar A, et al. Vitamin B12-do you know everything. Journal of Evolution of Med Dent Sci. 2020;9(42):3139-47.
  46. Google Scholar, Cross Ref

  47. Butola LK, Jha RK, Ambad R, et al. Vitamin B12 Deficit Status among Type 2 Diabetes Mellitus Patients-A Review. J Evolution Med Dent Sci. 2021.
  48. Google Scholar, Cross Ref

  49. Ali W, Ahmad I, Srivastava VK, et al. Serum zinc levels and its association with vitamin A levels among tuberculosis patients. J Nat Sci biol Med. 2014;5(1):130.
  50. Indexed at, Google Scholar, Cross Ref

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