178. RAT TESTICULAR MACROPHAGES EXHIBIT AN 'ALTERNATIVELY ACTIVATED' RESPONSE TO LIPOPOLYSACCHARIDE (LPS), INTERFERON-Γ (IFNΓ) AND INTERLEUKIN-4 (IL-4), CONSISTENT WITH IMMUNE PRIVILEGE

2009 ◽  
Vol 21 (9) ◽  
pp. 96
Author(s):  
W. R. Winnall ◽  
J. A. Muir ◽  
M. P. Hedger
Keyword(s):  
Inflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Constitutive Expression ◽  
Low Levels ◽  
Anti Inflammatory ◽  
M2 Phenotype ◽  
Testicular Macrophages ◽  
Alternatively Activated ◽  
Pro Inflammatory Cytokines

Testicular macrophages (TMs) are implicated both in the response of the testis to invading pathogens and supporting the immunosuppressive environment that protects developing germ cells (immunoprivilege). Macrophages are classified into two general phenotypes: “classically activated” (M1), which undergo inflammatory responses to LPS and IFNg, and “alternatively activated” (M2), defined by anti-inflammatory activity and regulated by IL-4. Our aim was to establish whether TMs have an M2 phenotype, consistent with immunoprivilege. Rat TMs and bone marrow-derived macrophages (BMMs) were isolated from adult rats, and cultured with LPS, IFNg and/or IL-4 for 2-3h. mRNA expression was measured by real-time RT-PCR and protein production was measured by ELISAs. Compared with BMMs, TMs stimulated with LPS and IFNg, either individually or in combination, expressed low levels of pro-inflammatory cytokines, such as IL-1β, IL-1α and tumour necrosis factor-α, intermediate levels of IL-6, but much greater levels (8-fold) of the anti-inflammatory cytokine, IL-10. TMs also displayed elevated constitutive expression of IL-10 and responded to IL-4, unlike BMMs. However, TMs expressed relatively low levels of another immunoregulatory cytokine, transforming growth factor-β1. After FACS-sorting of TMs using an antibody to CD163, a surface marker associated with M1-M2 progression, CD163+ TMs produced high levels of IL-10 constitutively and after stimulation, whereas CD163- cells produced little or no IL-10. Unexpectedly, both CD163- and CD163+ TMs expressed similar levels of most pro-inflammatory genes. These data indicate polarisation of TMs towards the M2 phenotype, characterised by production of IL-10 and responsiveness to IL-4, although the polarised TMs continue to express pro-inflammatory cytokines, albeit at significantly lower levels than other macrophages. The M2 phenotype is consistent with a role in testicular immunosuppression, but may also contribute to fibrosis, which is associated with testicular responses to vasectomy, cryptorchisism and infertility.

scholarly journals 13 Lipocalin 2 exerts protective activity by alleviating inflammatory responses

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 17-19
Author(s):  
Shuhui Li
Keyword(s):  
Inflammatory Cytokines ◽  
Protective Factor ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lipocalin 2 ◽  
Continuous Increase ◽  
Raw264.7 Macrophages ◽  
Arginase 1 ◽  
Anti Inflammatory

Abstract Lipocalin 2 (Lcn2) is an essential component of the innate immune system and exerts significant immunomodulatory effects in vitro. The aim of current study was to investigate the expression profile of Lcn2 during inflammatory process and explore the role of Lcn2 in the anti-inflammatory responses. Western blot, real-time quantitative PCR, immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA) were employed. Firstly, we evaluated the temporospatial expression of Lcn2 of mice after inflammatory stimuli by lipopolysaccharides (LPS). In vivo, LPS induced both mRNA and protein levels of Lcn2 significantly (P < 0.01) in liver, jejunum and ileum. Lcn2 exhibited a continuous increase by 8 h and peaked by 24 h post challenges. Secondly, we challenged Lcn2-deficient (Lcn2-/-) mice and wild-type (WT) mice with peripheral LPS and determined effects on inflammation. In contrast to WT mice, Lcn2-/- mice showed distinct inflammatory injury in liver, jejunum, ileum and spleen with significantly elevated pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-1b (IL-1b) and decreased anti-inflammatory cytokine interleukin-10 (IL-10). Thirdly, we isolated bone marrow-derived macrophages (BMDM) from Lcn2-/- mice and WT mice to evaluate their functions. After LPS challenge, Lcn2-/- BMDM showed aggravated inflammatory reaction as pro-inflammatory factors tumour necrosis factor-α (TNF-α), IL-6, IL-1b and inducible nitric oxide synthase (iNOS) increased (P < 0.05) while anti-inflammatory cytokines IL-10, transforming growth factor β1 (TGF-β1) and arginase-1(Arg-1) decreased significantly (P < 0.05) compared with WT BMDM. This phenomenon could be relieved when adding recombinant Lcn2 (P < 0.05). The exogenous addition of Lcn2 on mice RAW264.7 macrophages stimulated by LPS also conformed this point. These findings demonstrated that Lcn2 served as a potent protective factor in response to systemic inflammation, and elevated Lcn2 expression during inflammatory conditions was presumed to play an effective role in alleviating inflammatory responses.

IL-35 Is a Novel Responsive Anti-Inflammatory Cytokine - A New System of Categorizing Anti-Inflammatory Cytokines

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5197-5197
Author(s):  
Xiao-Feng Yang ◽  
Xinyuan Li ◽  
Jietang Mai ◽  
Anthony Virtue ◽  
Ying Yin ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Conflicts Of Interest ◽  
Expression Profiles ◽  
Constitutive Expression ◽  
Tissue Expression ◽  
Experimental Database ◽  
Molecular Events ◽  
Anti Inflammatory ◽  
New System

Abstract Abstract 5197 It remains unknown whether newly identified anti-inflammatory/immunosuppressive cytokine interleukin-35 (IL-35) is different from other anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF)-β in terms of inhibition of inflammation initiation and suppression of full-blown inflammation. Using experimental database mining and statistical analysis methods we developed, we examined the tissue expression profiles and regulatory mechanisms of IL-35 in comparison to other anti-inflammatory cytokines. Our results suggest that in contrast to TGF-β, IL-35 is not constitutively expressed in human tissues but it is inducible in response to inflammatory stimuli. We also provide structural evidence that AU-rich element (ARE) binding proteins and microRNAs target IL-35 subunit transcripts, by which IL-35 may achieve non-constitutive expression status. Furthermore, we propose a new system to categorize anti-inflammatory cytokines into two groups: (1) the house-keeping cytokines, such as TGF-β, inhibit the initiation of inflammation whereas (2) the responsive cytokines including IL-35 suppress inflammation in full-blown stage. Our in-depth analyses of molecular events that regulate the production of IL-35 as well as the new categorization system of anti-inflammatory cytokines are important for the design of new strategies of immune therapies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Effects of New Zealand Grown Ginseng Fractions on Cytokine Production from Human Monocytic THP-1 Cells

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1158
Author(s):  
Wei Chen ◽  
Prabhu Balan ◽  
David G. Popovich
Keyword(s):  
New Zealand ◽  
Inflammatory Cytokines ◽  
Transforming Growth Factor Beta ◽  
Inflammatory Cytokine ◽  
Transforming Growth Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Pro-inflammatory cytokines and anti-inflammatory cytokines are important mediators that regulate the inflammatory response in inflammation-related diseases. The aim of this study is to evaluate different New Zealand (NZ)-grown ginseng fractions on the productions of pro-inflammatory and anti-inflammatory cytokines in human monocytic THP-1 cells. Four NZ-grown ginseng fractions, including total ginseng extract (TGE), non-ginsenoside fraction extract (NGE), high-polar ginsenoside fraction extract (HPG), and less-polar ginsenoside fraction extract (LPG), were prepared and the ginsenoside compositions of extracts were analyzed by HPLC using 19 ginsenoside reference standards. The THP-1 cells were pre-treated with different concentrations of TGE, NGE, HPG, and LPG, and were then stimulated with lipopolysaccharide (LPS). The levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and anti-inflammatory cytokines, such as interleukin-10 (IL-10), and transforming growth factor beta-1 (TGF-β1), were determined by enzyme-linked immunosorbent assay (ELISA). TGE at 400 µg/mL significantly inhibited LPS-induced TNF-α and IL-6 productions. NGE did not show any effects on inflammatory secretion except inhibited IL-6 production at a high dose. Furthermore, LPG displayed a stronger effect than HPG on inhibiting pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) productions. Particularly, 100 µg/mL LPG not only significantly inhibited the production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, but also remarkably enhanced the production of anti-inflammatory cytokine IL-10. NZ-grown ginseng exhibited anti-inflammatory effects in vitro, which is mainly attributed to ginsenoside fractions (particularly less-polar ginsenosides) rather than non-saponin fractions.

scholarly journals Inhibition of SIK2 and SIK3 during differentiation enhances the anti-inflammatory phenotype of macrophages

2017 ◽  
Vol 474 (4) ◽  
pp. 521-537 ◽  
Author(s):  
Nicola J. Darling ◽  
Rachel Toth ◽  
J. Simon C. Arthur ◽  
Kristopher Clark
Keyword(s):  
Inflammatory Cytokines ◽  
Drug Targets ◽  
Macrophage Polarization ◽  
Macrophage Phenotype ◽  
Integral Role ◽  
Inflammatory Phenotype ◽  
Low Levels ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Pro Inflammatory Cytokines

The salt-inducible kinases (SIKs) control a novel molecular switch regulating macrophage polarization. Pharmacological inhibition of the SIKs induces a macrophage phenotype characterized by the secretion of high levels of anti-inflammatory cytokines, including interleukin (IL)-10, and the secretion of very low levels of pro-inflammatory cytokines, such as tumour necrosis factor α. The SIKs, therefore, represent attractive new drug targets for the treatment of macrophage-driven diseases, but which of the three isoforms, SIK1, SIK2 or SIK3, would be appropriate to target remains unknown. To address this question, we developed knock-in (KI) mice for SIK1, SIK2 and SIK3, in which we introduced a mutation that renders the enzymes catalytically inactive. Characterization of primary macrophages from the single and double KI mice established that all three SIK isoforms, and in particular SIK2 and SIK3, contribute to macrophage polarization. Moreover, we discovered that inhibition of SIK2 and SIK3 during macrophage differentiation greatly enhanced the production of IL-10 compared with their inhibition in mature macrophages. Interestingly, macrophages differentiated in the presence of SIK inhibitors, MRT199665 and HG-9-91-01, still produced very large amounts of IL-10, but very low levels of pro-inflammatory cytokines, even after the SIKs had been reactivated by removal of the drugs. Our data highlight an integral role for SIK2 and SIK3 in innate immunity by preventing the differentiation of macrophages into a potent and stable anti-inflammatory phenotype.

scholarly journals Anti-inflammatory Activity of a Polypeptide Fraction From Achyranthes bidentate in Amyloid β Oligomers Induced Model of Alzheimer’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangyu Ge ◽  
Yitong Wang ◽  
Shu Yu ◽  
Xuemin Cao ◽  
Yicong Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokines ◽  
Mrna Levels ◽  
Bv2 Microglia ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
The Brain ◽  
M2 Phenotype ◽  
Pro Inflammatory Cytokines

Neuroinflammation plays a crucial role in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and anti-inflammation has been considered as a potential therapeutic strategy. Achyranthes bidentate polypeptide fraction k (ABPPk) was shown to protect neurons from death and suppress microglia and astrocyte activation in PD model mice. However, how ABPPk regulates neuroinflammation to exert a neuroprotective role remains unclear. Toxic Aβ oligomers (AβOs) can trigger inflammatory response and play an important role in the pathogenesis of AD. In the present study, for the first time, we investigated the effects and underlying mechanisms of ABPPk on neuroinflammation in AβOs-induced models of AD. In vitro, ABPPk pretreatment dose-dependently inhibited AβOs-induced pro-inflammatory cytokines mRNA levels in BV2 and primary microglia. ABPPk pretreatment also reduced the neurotoxicity of BV2 microglia-conditioned media on primary hippocampal neurons. Furthermore, ABPPk down-regulated the AβOs-induced phosphorylation of IκBα and NF-κB p65 as well as the expression of NLRP3 in BV2 microglia. In vivo, ABPPk pre-administration significantly improved locomotor activity, alleviated memory deficits, and rescued neuronal degeneration and loss in the hippocampus of AβOs-injected mice. ABPPk inhibited the activation of microglia in hippocampal CA3 region and suppressed the activation of NF-κB as well as the expression of NLRP3, cleaved caspase-1, and ASC in the brain after AβOs injection. ABPPk hindered the release of pro-inflammatory cytokines and promoted the release of anti-inflammatory cytokines in the brain. Notably, the polarization experiment on BV2 microglia demonstrated that ABPPk inhibited M1-phenotype polarization and promoted M2-phenotype polarization by activating the LPS- or AβOs-impaired autophagy in microglia. Taken together, our observations indicate that ABPPk can restore the autophagy of microglia damaged by AβOs, thereby promoting M2-phenotype polarization and inhibiting M1-phenotype polarization, thus playing a role in regulating neuroinflammation and alleviating neurotoxicity.

scholarly journals Artemisia lactiflora Extracts Prevent Inflammatory Responses of Human Macrophages Stimulated with Charcoal Pyrolysis Smoke

2021 ◽  
Vol 26 ◽  
pp. 2515690X2110688
Author(s):  
Nateelak Kooltheat ◽  
Kamonrat Chujit ◽  
Kanjana Nuangnong ◽  
Nuttikarn Nokkaew ◽  
Kingkan Bunluepuech ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Biological Activities ◽  
Ethyl Acetate Fraction ◽  
Agricultural Industry ◽  
Inflammatory Genes ◽  
Genes Expression ◽  
Anti Inflammatory ◽  
Cytokines Secretion ◽  
Pro Inflammatory Cytokines

Artemisia lactiflora, a Chinese-origin plant, has been reported to have unique phytochemicals responsible for its medicinal properties. The growth of the agricultural industry emits air pollution, which has adverse effects on health. There are limited scientific reports on the biological activities of A. lactiflora. Studies on its activities and mechanisms may provide insight into its use in medicinal purposes to treat those health problems and conditions. In this study, leaves of A. lactiflora were extracted and fractioned with solvents of different polarities. Total phenolics, total flavonoids DPPH• scavenging, ABTS•+ scavenging, and cytotoxicity of A. lactiflora were assessed. Anti-inflammatory activities were evaluated by pre-treating macrophages with extract or fractions then induced inflammatory response by coconut shell pyrolysis smoke. Inflammatory responses were assessed by measuring pro-inflammatory genes expression and pro-inflammatory cytokines secretion. Among all extract and fractions of A. lactiflora, butanol fraction has the highest phenolic, flavonoid, and DPPH• scavenging activity. All extract and fractions significantly down-regulated pro-inflammatory genes expression ( RelA, TNF, IL6) and decreased pro-inflammatory cytokines secretion (TNF-α, IL-6), p < 0.0001, compared with pyrolysis smoke-induced macrophages. The ethyl acetate fraction showed the highest anti-inflammatory activity in decreasing pro-inflammatory cytokines secretion. These results may prove the anti-inflammatory activities of A. lactiflora through the inhibition of the NF-κB-dependent pathway. Taken together, this study first reported the anti-inflammatory activities of A. lactiflora. Thus, the plant can be used to prevent and treat inflammatory responses caused by highly oxidative pyrolysis smoke released from the re-utilization of agro-industrial leftovers.

Evaluation of Anti-Inflammatory Effects of Naproxen on Pro-Inflammatory Cytokines in COVID-19 Patients

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Abolnezhadian F ◽  
◽  
Khosravi AD ◽  
Makvandi M ◽  
Varnaseri M ◽  
...  
Keyword(s):  
Serum Level ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Gastrointestinal Symptoms ◽  
Serum Levels ◽  
World Health ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Health Organization ◽  
Pro Inflammatory Cytokines

The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection was declared by the World Health Organization as pandemic in the early 2020. The clinical spectrum of coronavirus disease 2019 (COVID-19) include asymptomatic and symptomatic cases, including dry cough, fatigue, fever, shortness of breath, and gastrointestinal symptoms. However, increased immune inflammatory responses to stimuli can result in the overproduction of pro-inflammatory cytokines, immunopathological complications and death in patients infected with COVID-19. Given the anti-inflammatory effects of Naproxen, this study evaluated the effect of naproxen on IL-1β, TNF-a, IL-6, IFN-γ and TGF-β in COVID-19 patients. According to the results, the serum levels of IFN-γ and TGF-β cytokines significantly decreased in the patients after the treatment with naproxen. In addition, the naproxen treatment was found effective in reducing the serum level of IL-6 and IL-1β in patients with COVID-19, though it did not significantly change the serum level of TNF-a. Overall, the findings demonstrated the effectiveness of naproxen on pro-inflammatory cytokines by regulating their serum levels in COVID-19 patients.

scholarly journals Discovery of 2-Substituted 3-Arylquinoline Derivatives as Potential Anti-Inflammatory Agents Through Inhibition of LPS-Induced Inflammatory Responses in Macrophages

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1162 ◽  
Author(s):  
Cheng-Yao Yang ◽  
Yung-Li Hung ◽  
Kai-Wei Tang ◽  
Shu-Chi Wang ◽  
Chih-Hua Tseng ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Hydrophobic Interactions ◽  
Activated Macrophages ◽  
Docking Analysis ◽  
Lead Compounds ◽  
Anti Inflammatory ◽  
Molecular Docking Analysis ◽  
Pro Inflammatory Cytokines

We describe herein the preparation of certain 2-substituted 3-arylquinoline derivatives and the evaluation of their anti-inflammatory effects in LPS-activated murine J774A.1 macrophage cells. Among these newly synthesized 2-substituted 3-arylquinoline derivatives, 2-(4-methoxy- benzoyl)-3-(3,4,5-trimethoxyphenyl)quinoline (18a) and 2-(4-fluorobenzoyl)-3-(3,4,5-trimethoxy- phenyl)quinoline (18b) are two of the most active compounds which can inhibit the production of NO at non-cytotoxic concentrations. Our results have also indicated that compounds 18a and 18b significantly decrease the secretion of pro-inflammatory cytokines (TNF-á and IL-6), inhibit the expression of iNOS, suppress the phosphorylation of MAPKs, and attenuate the activity of NF-êB by LPS-activated macrophages. Through molecular docking analysis, we found that 18b could fit into the middle of the TNF-á dimer and form hydrophobic interactions with Leu55, Leu57 chain A and B, Tyr59, Val123 chain B and D, Ile 155. These results suggest that both 18a and 18b are potential lead compounds in inhibiting LPS-induced inflammatory responses. Further structural optimization to discover novel anti-inflammatory agents is ongoing.

scholarly journals Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Inflammatory Responses ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Autophagy Inhibition ◽  
Pro Inflammatory Cytokines

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

scholarly journals Computational Identification of Potential Anti-Inflammatory Natural Compounds Targeting the p38 Mitogen-Activated Protein Kinase (MAPK): Implications for COVID-19-Induced Cytokine Storm

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 653
Author(s):  
Seth O. Asiedu ◽  
Samuel K. Kwofie ◽  
Emmanuel Broni ◽  
Michael D. Wilson
Keyword(s):  
Molecular Docking ◽  
P38 Mapk ◽  
Inflammatory Cytokines ◽  
Binding Energies ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Activity ◽  
Computational Techniques ◽  
Cytokine Storm ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Severely ill coronavirus disease 2019 (COVID-19) patients show elevated concentrations of pro-inflammatory cytokines, a situation commonly known as a cytokine storm. The p38 MAPK receptor is considered a plausible therapeutic target because of its involvement in the platelet activation processes leading to inflammation. This study aimed to identify potential natural product-derived inhibitory molecules against the p38α MAPK receptor to mitigate the eliciting of pro-inflammatory cytokines using computational techniques. The 3D X-ray structure of the receptor with PDB ID 3ZS5 was energy minimized using GROMACS and used for molecular docking via AutoDock Vina. The molecular docking was validated with an acceptable area under the curve (AUC) of 0.704, which was computed from the receiver operating characteristic (ROC) curve. A compendium of 38,271 natural products originating from Africa and China together with eleven known p38 MAPK inhibitors were screened against the receptor. Four potential lead compounds ZINC1691180, ZINC5519433, ZINC4520996 and ZINC5733756 were identified. The compounds formed strong intermolecular bonds with critical residues Val38, Ala51, Lys53, Thr106, Leu108, Met109 and Phe169. Additionally, they exhibited appreciably low binding energies which were corroborated via molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations. The compounds were also predicted to have plausible pharmacological profiles with insignificant toxicity. The molecules were also predicted to be anti-inflammatory, kinase inhibitors, antiviral, platelet aggregation inhibitors, and immunosuppressive, with probable activity (Pa) greater than probable inactivity (Pi). ZINC5733756 is structurally similar to estradiol with a Tanimoto coefficient value of 0.73, which exhibits anti-inflammatory activity by targeting the activation of Nrf2. Similarly, ZINC1691180 has been reported to elicit anti-inflammatory activity in vitro. The compounds may serve as scaffolds for the design of potential biotherapeutic molecules against the cytokine storm associated with COVID-19.

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