Discovery of Immunomodulators from Plant Kingdom Targeting IL-6 for the Effective Management Therapy of SARS-CoV-2

Jump To References Section

Authors

  • Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, The Nilgiris – 643001, Tamil Nadu ,IN
  • Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, The Nilgiris – 643001, Tamil Nadu ,IN
  • Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, The Nilgiris – 643001, Tamil Nadu ,IN
  • Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, The Nilgiris – 643001, Tamil Nadu ,IN
  • Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, The Nilgiris – 643001, Tamil Nadu ,IN
  • Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, The Nilgiris – 643001, Tamil Nadu ,IN
  • Department of Biotechnology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, The Nilgiris – 643001, Tamil Nadu ,IN

DOI:

https://doi.org/10.18311/jnr/2022/28798

Keywords:

Covid-19, IL-6, Cytokine Release Syndrome, Secondary Metabolites
Immunomodulation

Abstract

The present study was conducted because of the recent scenario of this pandemic coronavirus outbreak worldwide. Currently, this disease cannot be treated through specific vaccines and therapeutic medicines. While many vaccines are being investigated, it would take some time for these to be accessible to the masses. Eventual evidence indicates that many COVID-19 patients may die from an irregular release of cytokines called as Cytokine Release Syndrome (CRS) due to the excessive reaction of their immune systems. In worsening patients with COVID-19, CRS played a significant role, from pneumonia via ARDS to cumulative systemic inflammation and eventually to a failing of the multi-system organ. In COVID-19 individuals, a large number of cytokines, including IL-6, IL-1, IL-2, IL-10, TNF- ?, and IFN- ?, participate in the ‘cytokine storm,’ but IL-6, whose higher serum levels are associated with respiratory failure, ARDS, and adverse clinical outcomes, tends to be a critical factor. In China, the COVID-19 mortality indicator has been tested by a multi-centre retrospective analysis in 150 COVID-19 patients. The study analysed that 82 cases are resolved from COVID-19 and 68 cases are dead due to enhancement of IL-6 levels in the serum. In this research, the secondary plant metabolites from Indian traditional medicine are identified through a computational technique and the selected seedling metabolite is sealed to block the IL-6 receptor.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Downloads

Published

2022-04-19

How to Cite

Krishna Swaroop, A., Nagarjuna, P., Naresh, P., Shyam Sundar, P., Jubie, S., Natarajan, J., & Vasanth, P. (2022). Discovery of Immunomodulators from Plant Kingdom Targeting IL-6 for the Effective Management Therapy of SARS-CoV-2. Journal of Natural Remedies, 22(2), 249–260. https://doi.org/10.18311/jnr/2022/28798

Issue

Section

Short Communication
Received 2021-10-09
Accepted 2022-02-22
Published 2022-04-19

 

References

Abbasifard M, Khorramdelazad H. The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics. Life Sci. 2020; 257. https://doi.org/10.1016/j.lfs.2020.118097. PMid:32679148. PMCid:PMC7361088

Tang Y, Liu J, Zhang D, Xu Z, Ji J, Wen C. Cytokine Storm in COVID-19: The Current evidence and treatment strategies. Front Immunol. 2020; 11(July):1–13. https://doi.org/10.3389/fimmu.2020.01708. PMid:32754163. PMCid:PMC7365923

Rana MM. Cytokine storm in COVID-19: Potential therapeutics for immunomodulation. J Res Clin Med. 2020; 8(1):38. https://doi.org/10.34172/jrcm.2020.038

Zhang C, Wu Z, Li J-W, Zhao H, Wang G-Q. Cytokine release syndrome in severe COVID-19: Interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020; 55(5):105954. https://doi.org/10.1016/j.ijantimicag.2020.105954. PMid:32234467. PMCid:PMC7118634

Sinha P, Matthay MA, Calfee CS. Is a “Cytokine Storm” relevant to COVID-19? JAMA Intern Med. 2020; 180(9):1152. https://doi.org/10.1001/jamainternmed.2020.3313. PMid:32602883.

Liu B, Li M, Zhou Z, Guan X, Xiang Y. Can we use interleukin- 6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J Autoimmun. 2020; 111:102452. https://doi.org/10.1016/j.jaut.2020.102452. PMid:32291137. PMCid:PMC7151347

Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020; 9(1):1123–30. https://doi.org/10.1080/22221751.2020.1770129. PMid:32475230. PMCid:PMC7473317

Copaescu A, Smibert O, Gibson A, Phillips EJ, Trubiano JA. The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection. J Allergy Clin Immunol. 2020; 146(3):518–34. https://doi.org/10.1016/j.jaci.2020.07.001. PMid:32896310. PMCid:PMC7471766

Chen X, Zhao B, Qu Y, Chen Y, Xiong J, Feng Y, et al. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL- 6) level in critically ill COVID-19 patients. Clin Infect Dis. 2020. https://doi.org/10.1101/2020.02.29.20029520

Chen LYC, Hoiland RL, Stukas S, Wellington CL, Sekhon MS. Confronting the controversy: Interleukin-6 and the COVID-19 cytokine storm syndrome. Eur Respir J. 2020; 56(4). https://doi.org/10.1183/13993003.03006-2020. PMid:32883678. PMCid:PMC7474149

Gubernatorova EO, Gorshkova EA, Polinova AI, Drutskaya MS. IL-6: relevance for immunopathology of SARS-CoV-2. Cytokine Growth Factor Rev. 2020; 53:13–24. https://doi.org/10.1016/j.cytogfr.2020.05.009. PMid:32475759. PMCid:PMC7237916

Rees C, Costin J, Fink R, Mcmichael M, Fontaine K, Isern S, et al. In vitro inhibition of dengue virus entry by p-sulfoxy- cinnamic acid and structurally related combinatorial chemistries. Antivir. Res. 2008; 80(2):135–42. https://doi.org/10.1016/j.antiviral.2008.05.007. PMid:18606464

Berman HM, Kleywegt GJ, Nakamura H, Markley JL. The protein data bank archive as an open data resource. J Comput Aided Mol Des. 2014; 28(10):1009–14. https://doi.org/10.1007/s10822-014-9770-y. PMid:25062767. PMCid:PMC4196035

Alhazmi HA, Najmi A, Javed SA, Sultana S, Al Bratty M, Makeen HA, et al. Medicinal plants and isolated molecules demonstrating immunomodulation activity as potential alternative therapies for viral diseases including COVID- 19. Front Immunol. 2021; 12:1721. https://doi.org/10.3389/fimmu.2021.637553. PMid:34054806. PMCid:PMC8155592

Wagner H. Immunomodulatory agents from plants. Part of the Progress in Inflammation Research book series (PIR). Springer Science & Business Media; 1999. https://doi.org/10.1007/978-3-0348-8763-2

Dahanukar SA, Thatte UM. Current status of Ayurveda in phytomedicine. Phytomedicine. 1997; 4(4):359–68. https://doi.org/10.1016/S0944-7113(97)80048-7

Dorsch W, Stuppner H, Wagner H, Gropp M, Demoulin S, Ring J. Antiasthmatic effects of Picrorhiza kurroa: Androsin prevents allergen-and PAF-induced bronchial obstruction in guinea pigs. Int Arch Allergy Immunol. 1991; 95(2–3):128–33. https://doi.org/10.1159/000235416. PMid:1718906

Jantan I, Ahmad W, Bukhari SNA. Plant-derived immunomodulators: An insight on their preclinical evaluation and clinical trials. Front Plant Sci. 2015; 6:655. https://doi.org/10.3389/fpls.2015.00655. PMid:26379683 PMCid:PMC4548092

Nair A, Chattopadhyay D, Saha B. Plant-derived immunomodulators. In: New look to phytomedicine. Elsevier; 2019. p. 435–99. https://doi.org/10.1016/B978-0-12-814619-4.00018-5. PMid:30794457

Swaroop AK, Mvnl C, S M, Subramanian G, Natarajan J, Selvaraj J. Plant derived immunomodulators: A Critical Review [Internet]. 2021. [cited 2021 Nov 9]. Available from: https://apb.tbzmed.ac.ir/Article/apb-32199. https://doi.org/10.34172/apb.2022.074

Akey KS, Jubie S, Vasanth P, Jeyaprakash M, Jawahar N. Dual modulation of IL-6 pathway by flavonoid-metal complexes as immune boosters for SARS-CoV-2 therapy. SPAST Abstracts. 2021; 1(01).

Cousins KR. Computer review of Chem Draw Ultra 12.0. J Am Chem Soc. 2011; 133(21):8388. https://doi.org/10.1021/ja204075s. PMid:21561109

Usha T, Goyal AK, Lubna S, Prashanth HP, Mohan TM, Pande V, et al. Identification of anti-cancer targets of eco-friendly waste punica granatum peel by dual reverse virtual screening and binding analysis. Asian Pac J Cancer Prev. 2015; 15(23):10345–50. https://doi.org/10.7314/APJCP.2014.15.23.10345. PMid:25556473

Sarvagalla S, Singh VK, Ke Y-Y, Shiao H-Y, Lin W-H, Hsieh H-P, et al. Identification of ligand efficient, fragment-like hits from an HTS library: Structure-based virtual screening and docking investigations of 2H- and 3H-pyrazolo tautomers for Aurora kinase A selectivity. J Comput Aided Mol Des. 2015; 29(1):89–100. https://doi.org/10.1007/s10822-014-9807-2. PMid:25344840

Geerts T, Vander Heyden Y. In Silico predictions of ADME-Tox properties: Drug absorption. Comb Chem High Throughput Screen. 2011; 14(5):339–61. https://doi.org/10.2174/138620711795508359. PMid:21470183

Naresh P, Selvaraj A, Sundar PS, Murugesan S, Sathianarayanan S, Namboori PKK, et al. Targeting a conserved pocket (n-octyl-β-D-glucoside) on the dengue virus envelope protein by small bioactive molecule inhibitors. J Biomol Struct Dyn. 2020; 1–13. https://doi.org/10.1080/073 91102.2020.1862707. PMid:33345726

Prabha T, Kapoor VK, Selvamani P, Latha S, Sivakumar T, Jubie S. Dual modulators of selected plant secondary metabolites targeting COVID-19 main protease and Interleukin-2: An in-silico approach based novel hypothesis. COVID. 2021; 2(2):223–34. https://doi.org/10.2174/2666796701999200929124556