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Diseases","award":["DK125126"],"award-info":[{"award-number":["DK125126"]}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["AI162182"],"award-info":[{"award-number":["AI162182"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nearly six million people worldwide have died from the coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although COVID-19 vaccines are largely successful in reducing the severity of the disease and deaths, the decline in vaccine-induced immunity over time and the continuing emergence of new viral variants or mutations underscore the need for an alternative strategy for developing broad-spectrum host-mediated therapeutics against SARS-CoV-2. A key feature of severe COVID-19 is dysregulated innate immune signaling, culminating in a high expression of numerous pro-inflammatory cytokines and chemokines and a lack of antiviral interferons (IFNs), particularly type I (alpha and beta) and type III (lambda). As a natural host defense, the myeloid differentiation primary response protein, MyD88, plays pivotal roles in innate and acquired immune responses via the signal transduction pathways of Toll-like receptors (TLRs), a type of pathogen recognition receptors (PRRs). However, recent studies have highlighted that infection with viruses upregulates MyD88 expression and impairs the host antiviral response by negatively regulating type I IFN. Galectin-3 (Gal3), another key player in viral infections, has been shown to modulate the host immune response by regulating viral entry and activating TLRs, the NLRP3 inflammasome, and NF-\u03baB, resulting in the release of pro-inflammatory cytokines and contributing to the overall inflammatory response, the so-called \u201ccytokine storm\u201d. These studies suggest that the specific inhibition of MyD88 and Gal3 could be a promising therapy for COVID-19. This review presents future directions for MyD88- and Gal3-targeted antiviral drug discovery, highlighting the potential to restore host immunity in SARS-CoV-2 infections.<\/jats:p>","DOI":"10.3390\/ijms25158421","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T12:38:20Z","timestamp":1722515900000},"page":"8421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Targeting Myeloid Differentiation Primary Response Protein 88 (MyD88) and Galectin-3 to Develop Broad-Spectrum Host-Mediated Therapeutics against SARS-CoV-2"],"prefix":"10.3390","volume":"25","author":[{"given":"Kamal U.","family":"Saikh","sequence":"first","affiliation":[{"name":"GlycoMantra Inc., bwtech South of the University of Maryland Baltimore County, 1450 South Rolling Road, Baltimore, MD 21227, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khairul","family":"Anam","sequence":"additional","affiliation":[{"name":"GlycoMantra Inc., bwtech South of the University of Maryland Baltimore County, 1450 South Rolling Road, Baltimore, MD 21227, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Halima","family":"Sultana","sequence":"additional","affiliation":[{"name":"GlycoMantra Inc., bwtech South of the University of Maryland Baltimore County, 1450 South Rolling Road, Baltimore, MD 21227, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakin","family":"Ahmed","sequence":"additional","affiliation":[{"name":"GlycoMantra Inc., bwtech South of the University of Maryland Baltimore County, 1450 South Rolling Road, Baltimore, MD 21227, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simran","family":"Kumar","sequence":"additional","affiliation":[{"name":"GlycoMantra Inc., bwtech South of the University of Maryland Baltimore County, 1450 South Rolling Road, Baltimore, MD 21227, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"GlycoMantra Inc., bwtech South of the University of Maryland Baltimore County, 1450 South Rolling Road, Baltimore, MD 21227, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hafiz","family":"Ahmed","sequence":"additional","affiliation":[{"name":"GlycoMantra Inc., bwtech South of the University of Maryland Baltimore County, 1450 South Rolling Road, Baltimore, MD 21227, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus biology and replication: Implications for SARS-CoV-2","volume":"19","author":"Kratzel","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3810","DOI":"10.1038\/s41467-020-17665-9","article-title":"Activation and evasion of type I interferon responses by SARS-CoV-2","volume":"11","author":"Lei","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"108234","DOI":"10.1016\/j.celrep.2020.108234","article-title":"Evasion of Type I Interferon by SARS-CoV-2","volume":"33","author":"Xia","year":"2020","journal-title":"Cell Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7092","DOI":"10.1038\/s41467-021-27318-0","article-title":"Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2","volume":"12","author":"Hatton","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"eadg0033","DOI":"10.1126\/sciimmunol.adg0033","article-title":"Modulation of type I interferon responses potently inhibits SARS-CoV-2 replication and inflammation in rhesus macaques","volume":"8","author":"Viox","year":"2023","journal-title":"Sci. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nri1900","article-title":"IRFs: Master regulators of signaling by Toll-like receptors and cytosolic pattern-recognition receptors","volume":"6","author":"Honda","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.immuni.2010.03.012","article-title":"Intracellular toll-like receptors","volume":"32","author":"Blasius","year":"2010","journal-title":"Immunity"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1146\/annurev.immunol.21.120601.141126","article-title":"Toll-like receptors","volume":"21","author":"Takeda","year":"2003","journal-title":"Ann. Rev. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s12026-021-09188-2","article-title":"MyD88 and beyond: A perspective on MyD88-targeted therapeutic approach for modulation of host immunity","volume":"69","author":"Saikh","year":"2021","journal-title":"Immunol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10260","DOI":"10.1073\/pnas.0812956106","article-title":"Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling","volume":"106","author":"Ohnishi","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"97","DOI":"10.12703\/P6-97","article-title":"MyD88: A central player in innate immune signaling","volume":"6","author":"Deguine","year":"2014","journal-title":"F1000Prime Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Stojanovic, B.S., Stojanovic, B., Milovanovic, J., Arsenijevi\u0107, A., Dimitrijevic Stojanovic, M., Arsenijevic, N., and Milovanovic, M. (2023). The Pivotal Role of Galectin-3 in Viral Infection: A Multifaceted Player in Host-Pathogen Interactions. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119617"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/nrmicro2146","article-title":"Roles of galectins in infection","volume":"7","author":"Vasta","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_16","first-page":"9247574","article-title":"The Many Roles of Galectin-3, a Multifaceted Molecule, in Innate Immune Responses against Pathogens","volume":"2017","author":"Ortega","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41577-022-00829-7","article-title":"The role of galectins in immunity and infection","volume":"23","author":"Liu","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1006\/geno.1997.4940","article-title":"Genetic structure and chromosomal mapping of MyD88","volume":"45","author":"Hardiman","year":"1997","journal-title":"Genomics"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Alcoceba, M., Garc\u00eda-\u00c1lvarez, M., Medina, A., Maldonado, R., Gonz\u00e1lez-Calle, V., Chill\u00f3n, M.C., Sarasquete, M.E., Gonz\u00e1lez, M., Garc\u00eda-Sanz, R., and Jim\u00e9nez, C. (2022). MYD88 Mutations: Transforming the Landscape of IgM Monoclonal Gammopathies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105570"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S1097-2765(00)80136-7","article-title":"MyD88 is an adaptor protein in the Toll\/IL-1 receptor family signaling pathways","volume":"2","author":"Medzhitov","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Olson, M.A., Lee, M.S., Kissner, T.L., Alam, S., Waugh, D.S., and Saikh, K.U. (2015). Discovery of Small Molecule Inhibitors of MyD88-Dependent Signaling Pathways using a Computational Screen. Sci. Rep., 5.","DOI":"10.1038\/srep14246"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"776","DOI":"10.2174\/138920312804871148","article-title":"Suppression of TLR signaling by targeting TIR domain-containing proteins","volume":"13","author":"Fekonja","year":"2012","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.4049\/jimmunol.1100515","article-title":"The Role of Intermediary Domain of MyD88 in Cell Activation and Therapeutic Inhibition of TLRs","volume":"187","author":"Avbelj","year":"2011","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/35040600","article-title":"Structural Basis for Signal Transduction by the Toll\/interleukin-I receptor domains","volume":"408","author":"Xu","year":"2000","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104854","DOI":"10.1016\/j.antiviral.2020.104854","article-title":"A small molecule inhibitor of MyD88 exhibits broad spectrum antiviral activity by up regulation of type I interferon","volume":"181","author":"Saikh","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1126\/science.278.5343.1612","article-title":"IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling","volume":"278","author":"Muzio","year":"1997","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1161\/CIRCULATIONAHA.105.536433","article-title":"Myeloid differentiation factor-88 plays a crucial role in the pathogenesis of Coxsackievirus B3 induced myocarditis and influences type I interferon production","volume":"112","author":"Fuse","year":"2005","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1099\/vir.0.010280-0","article-title":"Oligonucleotide array analysis of Toll-like receptors and associated signaling genes in Venezuelan equine encephalitis virus-infected mouse brain","volume":"2009","author":"Sharma","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1016\/j.celrep.2016.01.049","article-title":"Differential regulation of interferon responses by ebola and Marburg virus VP35 proteins","volume":"14","author":"Edwards","year":"2016","journal-title":"Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1002\/eji.201040547","article-title":"TLR3-mediated IFN-\u03b2 gene induction is negatively regulated by the TLR adaptor MyD88 adaptor-like","volume":"40","author":"Siednienko","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.4049\/jimmunol.1003093","article-title":"Absence of MyD88 results in enhanced TLR3-dependent phosphorylation of IRF3 and increased IFN-\u03b2 and RANTES production","volume":"186","author":"Siednienko","year":"2011","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.chom.2016.01.006","article-title":"The Evolution of antiviral defense systems","volume":"19","author":"TenOver","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.immunol.20.083001.084359","article-title":"Innate immune recognition","volume":"20","author":"Janeway","year":"2002","journal-title":"Annu. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1146\/annurev-immunol-032713-120156","article-title":"Innate immune sensing and signaling of cytosolic nucleic acids","volume":"32","author":"Wu","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1111\/j.1462-5822.2006.00716.x","article-title":"Interferon signaling network in innate defense","volume":"8","author":"Takeda","year":"2006","journal-title":"Cell Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1089\/107999002760274845","article-title":"IFN- alpha beta receptor interactions to biologic outcomes; understanding the circuitry","volume":"22","author":"Brierle","year":"2002","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.immuni.2019.03.025","article-title":"Shared and distinct functions of type I and type III interferons","volume":"50","author":"Lazear","year":"2019","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1146\/annurev-immunol-042718-041356","article-title":"Double stranded RNA sensors and modulators of innate immunity","volume":"37","author":"Hur","year":"2019","journal-title":"Annu. Rev. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.it.2012.01.004","article-title":"The yin and yang of viruses and Interferons","volume":"33","author":"Wang","year":"2012","journal-title":"Trends Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1517\/14712598.2010.521495","article-title":"Interferons as potential adjuvants in prophylactic vaccines","volume":"10","author":"Toporovski","year":"2010","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41590-020-00840-x","article-title":"Untuned antiviral immunity in COVID-19 revealed by temporal type I\/III interferon patterns and flu comparison","volume":"22","author":"Galani","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10479","DOI":"10.1016\/j.antiviral.2020.104791","article-title":"Type 1 interferons as a potential treatment against COVID-19","volume":"178","author":"Sallard","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1146\/annurev.immunol.19.1.623","article-title":"IRF family of transcription factors as regulators of host defense","volume":"19","author":"Taniguchi","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2986","DOI":"10.1128\/MCB.18.5.2986","article-title":"Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome mediated degradation","volume":"18","author":"Lin","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S1359-6101(97)00019-1","article-title":"The growing family of interferon regulatory factors","volume":"8","author":"Nguyen","year":"1997","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-1119(99)00262-0","article-title":"Interferon regulatory factors: The next generation","volume":"237","author":"Mamane","year":"1999","journal-title":"Gene"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/nature03464","article-title":"IRF-7 is he master regulator of type-1 interferon-dependent immune responses","volume":"434","author":"Honda","year":"2005","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ni921","article-title":"IKK epsilon and TBK1 are essential components of the IRF3 signaling pathway","volume":"4","author":"Fitzgerald","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5886","DOI":"10.1128\/JVI.00262-16","article-title":"HIV-1 Tat Protein Activates both the MyD88 and TRIF Pathways to Induce Tumor Necrosis Factor Alpha Interleukin-10 in Human Monocytes","volume":"90","author":"Leghmari","year":"2016","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1161\/HYPERTENSIONAHA.115.06011","article-title":"Dual Activation of TRIF and MyD88 Adaptor Proteins by Angiotensin II Evokes Opposing Effects on Pressure, Cardiac Hypertrophy, and Inflammatory Gene Expression","volume":"66","author":"Singh","year":"2015","journal-title":"Hypertension"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3642","DOI":"10.4049\/jimmunol.0901140","article-title":"MyD88 adaptor like is not essential for TLR2 signaling and inhibits signaling by TLR3","volume":"183","author":"Kenny","year":"2009","journal-title":"J. Immunol."},{"key":"ref_52","first-page":"3988","article-title":"MyD88 functions as a negative regulator of TLR3\/TRIFinduced corneal inflammation by inhibiting activation of c-Jun N-terminal kinase","volume":"278","author":"Johnson","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1084\/jem.20081210","article-title":"Differential recognition of double-stranded RNA by RIG-I-like receptors in antiviral immunity","volume":"205","author":"Saito","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1089\/jir.2013.0035","article-title":"Ebola virus-like particles stimulate Type I interferons and pro-inflammatory cytokine expression through the toll-like receptors and interferon signaling pathways","volume":"34","author":"Ayithan","year":"2014","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1089\/vim.2021.0020","article-title":"Cells Stimulated with More Than One Toll-Like Receptor-Ligand in the Presence of a MyD88 Inhibitor Augmented Interferon-\u03b2 via MyD88-Independent Signaling Pathway","volume":"34","author":"Saikh","year":"2021","journal-title":"Viral Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ribero, M.S., Jouvenet, N., Dreux, M., and Nisole, S. (2020). Interplay between SARS-CoV-2 and type I interferon response. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008737"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e00638-15","DOI":"10.1128\/mBio.00638-15","article-title":"Toll-like receptor signaling via TRIF contributes to a protective Innate Immune Response to Sever acute respiratory syndrome coronavirus infection","volume":"6","author":"Totura","year":"2015","journal-title":"mBio"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.thromres.2020.06.029","article-title":"The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management","volume":"194","author":"Diamond","year":"2020","journal-title":"Thromb Res."},{"key":"ref_59","first-page":"136","article-title":"Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19","volume":"181","author":"Liu","year":"2020","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S401","DOI":"10.1093\/infdis\/jiz602","article-title":"Control of nipah virus infection in mice by the host adaptors mitrochondrial antiviral signaling protein (MAVS) and myeloid differentiation primary response 88 (MyD88)","volume":"221","author":"Iampietro","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Zhou, Z.X., Zhang, B.C., and Sun, L. (2014). Poly (I:C) induces antiviral immune responses in Japanese flounder (Paralichthys olivaceus) that require TLR3 and MDA5 and is negatively regulated by MyD88. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112918"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nri3581","article-title":"Regulation of type I interferon responses","volume":"14","author":"Ivashkiv","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"827","DOI":"10.3389\/fimmu.2020.00827","article-title":"Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19)","volume":"11","author":"Diao","year":"2020","journal-title":"Front Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41423-020-0402-2","article-title":"Functional exhaustion of antiviral lymphocytes in COVID-19 patients","volume":"17","author":"Zheng","year":"2020","journal-title":"Cell Mol. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Martinez-Gil, L., Ayllon, J., Ortigoza, M.B., Garcia-satre, A., Shaw, M.L., and Palese, P. (2012). Identification of small molecules with type I interferon inducing properties by High-throughput Screening. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049049"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Suckling, C.J., Alam, S., Olson, M.A., Saikh, K.U., Harnett, M.M., and Harnett, W. (2018). Small Molecule Analogues of the parasitic worm product ES-62 interact with the TIR domain domain of MyD88 to inhibit pro-inflammatory signaling. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-20388-z"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1006\/abbi.1997.0447","article-title":"The HumanLGALS3 (Galectin-3) Gene: Determination of the Gene Structure and Functional Characterization of the Promoter","volume":"349","author":"Kadrofske","year":"1998","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_68","first-page":"6239","article-title":"The NH2 terminus of galectin-3 governs cellular compartmentalization and functions in cancer cells","volume":"59","author":"Gong","year":"1999","journal-title":"Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.bbagen.2005.12.020","article-title":"Galectin-3: An open-ended story","volume":"1760","author":"Dumic","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1007\/s00018-007-7044-8","article-title":"Galectins: Matricellular glycan-binding proteins linking cell adhesion, migration, and survival","volume":"64","author":"Elola","year":"2007","journal-title":"Cell Mol. Life Sci."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Ahmed, R., Anam, K., and Ahmed, H. (2023). Development of Galectin-3 Targeting Drugs for Therapeutic Applications in Various Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098116"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.12688\/f1000research.25979.2","article-title":"Immunopathology of galectin-3: An increasingly promising target in COVID-19","volume":"9","author":"Caniglia","year":"2020","journal-title":"F1000Research"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1093\/glycob\/cwu064","article-title":"Galectin-3 promotes HIV-1 budding via association with Alix and Gag p6","volume":"24","author":"Wang","year":"2014","journal-title":"Glycobiology"},{"key":"ref_74","first-page":"760","article-title":"Galectin-3 facilitates cell-to-cell HIV-1 transmission by altering the composition of membrane lipid rafts in CD4 T cells","volume":"32","author":"Wang","year":"2022","journal-title":"Glycobiology"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Kulkarni, R., and Prasad, A. (2017). Exosomes Derived from HIV-1 Infected DCs Mediate Viral trans-Infection via Fibronectin and Galectin-3. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-14817-8"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5841","DOI":"10.1128\/JVI.00166-13","article-title":"Binding of transmembrane mucins to galectin-3 limits herpesvirus 1 infection of human corneal keratinocytes","volume":"87","author":"Woodward","year":"2013","journal-title":"J. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molimm.2014.12.010","article-title":"Desialylation of airway epithelial cells during influenza virus infection enhances pneumococcal adhesion via galectin binding","volume":"65","author":"Banerjee","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.ajpath.2017.12.014","article-title":"Galectin-3 enhances avian H5N1 influenza a virus-induced pulmonary inflammation by promoting NLRP3 inflammasome activation","volume":"188","author":"Chen","year":"2018","journal-title":"Am. J. Pathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41586-020-2180-5","article-title":"Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor","volume":"581","author":"Lan","year":"2020","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"198058","DOI":"10.1016\/j.virusres.2020.198058","article-title":"Role of the GTNGTKR Motif in the N-Terminal Receptor-Binding Domain of the SARS-CoV-2 Spike Protein","volume":"286","author":"Behloul","year":"2020","journal-title":"Virus Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S2213-2600(20)30079-5","article-title":"Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia inWuhan, China: A single-centered, retrospective, observational study","volume":"8","author":"Yang","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical characteristics of coronavirus disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1111\/all.14238","article-title":"Clinical characteristics of 140 patients infected by SARS-CoV-2 in Wuhan, China","volume":"75","author":"Zhang","year":"2020","journal-title":"Allergy"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s00392-020-01626-9","article-title":"Prevalence and impact of cardiovascularmetabolic diseases on COVID-19 in China","volume":"109","author":"Li","year":"2020","journal-title":"Clin. Res. Cardiol."},{"key":"ref_85","first-page":"1499","article-title":"Structural myocardial alterations in diabetes and hypertension: The role of galectin-3","volume":"52","author":"Seferovic","year":"2014","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1515\/sjecr-2015-0057","article-title":"Galectin-3 in obesity and type 2 diabetes","volume":"16","author":"Pejnovic","year":"2015","journal-title":"Ser. J. Exp. Clin. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s40618-014-0222-2","article-title":"Increased levels of galectin-3 were associated with prediabetes and diabetes: New risk factor?","volume":"38","author":"Yilmaz","year":"2015","journal-title":"J. Endocrinol. Investig."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"61","DOI":"10.20517\/2574-1209.2016.10","article-title":"Galectin-3 as a potential biomarker of metabolic disorders and cardiovascular remodeling in patients with hypertension and type 2 diabetes","volume":"1","author":"Bobronnikova","year":"2017","journal-title":"Vessel. Plus"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"106556","DOI":"10.1016\/j.rmed.2021.106556","article-title":"Galectin-3 as prognostic biomarker in patients with COVID-19 acute respiratory failure","volume":"187","author":"Portacci","year":"2021","journal-title":"Respir. Med."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Cervantes-Alvarez, E., la Rosa, N.L., la Mora, M.S., Valdez-Sandoval, P., Palacios-Jimenez, M., Rodriguez-Alvarez, F., Vera-Maldonado, B.I., Aguirre-Aguilar, E., Escobar-Valderrama, J.M., and Alanis-Mendizabal, J. (2022). Galectin-3 as a potential prognostic biomarker of severe COVID-19 in SARS-CoV-2 infected patients. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-05968-4"},{"key":"ref_91","first-page":"e28805","article-title":"Galectin-3 as a Potential Prognostic Biomarker for COVID-19 Disease: A Case-Control Study","volume":"14","author":"Karsli","year":"2022","journal-title":"Cureus"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Gajovic, N., Markovic, S.S., Jurisevic, M., Jovanovic, M., Arsenijevic, N., Mijailovic, Z., Jovanovic, M., and Jovanovic, I. (2023). Galectin-3 as an important prognostic marker for COVID-19 severity. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-28797-5"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1093\/glycob\/cwaa042","article-title":"Deducing the N- and O-glycosylation profile of the spike protein of novel coronavirus SARS-CoV-2","volume":"30","author":"Shajahan","year":"2020","journal-title":"Glycobiology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/bs.aivir.2019.08.002","article-title":"Structural insights into coronavirus entry","volume":"105","author":"Tortorici","year":"2019","journal-title":"Adv. Virus Res."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Finkelstein, M.T., Mermelstein, A.G., Parker Miller, E., Seth, P.C., Stancofski, E.S.D., and Fera, D. (2021). Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies. Viruses, 13.","DOI":"10.3390\/v13010134"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1021\/acscentsci.0c01056","article-title":"Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein","volume":"6","author":"Casalino","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e9392","DOI":"10.7717\/peerj.9392","article-title":"A potential role for Galectin-3 inhibitors in the treatment of COVID-19","volume":"8","author":"Caniglia","year":"2020","journal-title":"PeerJ"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12985-022-01814-1","article-title":"COVID-19 infection: An overview on cytokine storm and related interventions","volume":"19","author":"Montazersaheb","year":"2022","journal-title":"Virol. J."},{"key":"ref_100","first-page":"824","article-title":"Potential Roles of Modified Pectin Targeting Galectin-3 against Severe Acute Respiratory Syndrome Coronavirus-2","volume":"4","author":"Reddy","year":"2021","journal-title":"J"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Zhou, W., Chen, X., Hu, Q., Chen, X., Chen, Y., and Huang, L. (2018). Galectin-3 activates TLR4\/NF-\u2000B signaling to promote lung adenocarcinoma cell proliferation through activating lncRNA-NEAT1 expression. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4461-z"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"104799","DOI":"10.1016\/j.micpath.2021.104799","article-title":"The pro-inflammatory cytokines in COVID-19 pathogenesis: What goes wrong?","volume":"153","author":"Darif","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Garcia-Revilla, J., Deierborg, T., Venero, J.L., and Boza-Serrano, A. (2020). Hyperinflammation and Fibrosis in Severe COVID-19 Patients: Galectin-3, a Target Molecule to Consider. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.02069"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Lin, C.Y., Yang, Z.S., Wang, W.H., Urbina, A.N., Lin, Y.T., Huang, J.C., Liu, F.T., and Wang, S.F. (2021). The Antiviral Role of Galectins toward Influenza A Virus Infection-An Alternative Strategy for Influenza Therapy. Pharmaceuticals, 14.","DOI":"10.3390\/ph14050490"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Arsenijevic, A., Stojanovic, B., Milovanovic, J., Arsenijevic, D., Arsenijevic, N., and Milovanovic, M. (2020). Galectin-3 in Inflammasome Activation and Primary Biliary Cholangitis Development. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21145097"},{"key":"ref_106","first-page":"9647","article-title":"Activation of the TLR4\/MyD88 signaling pathway contributes to the development of human hepatocellular carcinoma via upregulation of IL-23 and IL-17A","volume":"15","author":"Kang","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nri1391","article-title":"Toll-like receptor signalling","volume":"4","author":"Akira","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1042\/bst0310643","article-title":"The role of MyD88-like adapters in Toll-like receptor signal transduction","volume":"31","year":"2003","journal-title":"Biochem. Soc. Trans."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.chom.2020.05.008","article-title":"Type I and Type III Interferons\u2014Induction, Signaling, Evasion, and Application to Combat COVID-19","volume":"27","author":"Park","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41577-020-0346-x","article-title":"Dysregulation of type I interferon responses in COVID-19","volume":"20","author":"Acharya","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1126\/science.abc6027","article-title":"Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients","volume":"369","author":"Hadjadj","year":"2020","journal-title":"Science"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"7971","DOI":"10.1073\/pnas.0932746100","article-title":"A low molecular weight mimic of the TIR-domain inhibits interleukin 1 receptor-mediated responses","volume":"100","author":"Bartfai","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"31385","DOI":"10.1074\/jbc.M110.204982","article-title":"A small molecule that mimics the BB-loop in Toll\/IL-1 receptor domain of MyD88 attenuate Staphylococcal enterotoxin induced cytokine production and toxic shock in mice","volume":"286","author":"Kissner","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Kissner, T.L., Ruthel, G., Alam, S., Mann, E., Ajami, D.E., Rebek, M., Larkin, E.S., Fernandez, S., Ulrich, R.G., and Ping, S. (2012). Therapeutic inhibition of pro-infammatory signaling and toxicity to staphylococcal enterotoxin B by a synthetic dimeric BB-loop mimetic of MyD88. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040773"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/cbdd.12477","article-title":"Structure-based design and synthesis of a small molecule that exhibits anti-infammatory activity by inhibition of MyD88- mediated signaling to bacterial toxin exposure","volume":"86","author":"Alam","year":"2015","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_116","unstructured":"Saikh, K.U., Rebek, J.M., and Glass, P.J. (2017). Small Molecule Inhibitor of MyD88 for Therapeutic Treatment against Alphavirus and Staphylococcal Enterotoxin Infections and Toxin Exposure. (9,833,437 B2), US Patent."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"12626","DOI":"10.1021\/acs.jmedchem.2c00660","article-title":"Discovery and Optimization of the First Highly Effective and Orally Available Galectin-3 Inhibitors for Treatment of Fibrotic Disease","volume":"65","author":"Zetterberg","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Gaughan, E., Sethi, T., Quinn, T., Hirani, N., and Mills, A. (2021). GB0139, an inhaled small molecule inhibitor of galectin-3, in COVID-19 pneumonitis: A randomised, controlled, open-label, phase 2a experimental medicine trial of safety, pharmacokinetics, and potential therapeutic value. medRxiv.","DOI":"10.1101\/2021.12.21.21267983"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Sigamani, A., Mayo, K.H., Chen-Walden, H., Reddy, S., and Platt, D. (2022). Galectin approach to lower covid transmission\u2014Drug development for clinical use. medRxiv.","DOI":"10.1101\/2022.11.09.22282151"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"5052","DOI":"10.1073\/pnas.1202653110","article-title":"Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis","volume":"110","author":"Guha","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1080\/14728222.2018.1464139","article-title":"MyD88 as a therapeutic target for inflammatory diseases","volume":"25","author":"Padova","year":"2018","journal-title":"Expert. Opin. Ther. Targets"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8421\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:28:22Z","timestamp":1760110102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8421"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,1]]},"references-count":121,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158421"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158421","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,1]]}}}