Therapeutic strategies for COVID-19: progress and lessons learned

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(6), P. 449 - 475

Published: April 19, 2023

Language: Английский

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CD147 Sparks Atherosclerosis by Driving M1 Phenotype and Impairing Efferocytosis

Circulation Research, Journal Year: 2024, Volume and Issue: 134(2), P. 165 - 185

Published: Jan. 3, 2024

Atherosclerosis is a globally prevalent chronic inflammatory disease with high morbidity and mortality. The development of atherosclerotic lesions determined by macrophages. This study aimed to investigate the specific role myeloid-derived CD147 (cluster differentiation 147) in atherosclerosis its translational significance.

Language: Английский

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SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 4, 2024

T lymphocytes play a primary role in the adaptive antiviral immunity. Both lymphocytosis and lymphopenia were found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While indicates an active anti-viral response, is sign of poor prognosis. T-cells, essence, rarely express ACE2 receptors, making cause cell depletion enigmatic. Moreover, emerging strains posed immunological challenge, potentially alarming for next pandemic. Herein, we review how possible indirect direct key mechanisms could contribute SARS-CoV-2-associated-lymphopenia. The fundamental mechanism inflammatory cytokine storm elicited by viral infection, which alters host metabolism into more acidic state. This "hyperlactic acidemia" together suppresses T-cell proliferation triggers intrinsic/extrinsic apoptosis. SARS-CoV-2 infection also results shift from steady-state hematopoiesis stress hematopoiesis. Even low expression, presence cholesterol-rich lipid rafts on activated T-cells may enhance entry syncytia formation. Finally, indicate participation other receptors or auxiliary proteins that can work alone concert mechanisms. Therefore, address CD147-a novel route-for its new variants. CD147 not only expressed but it interacts co-partners orchestrate various biological processes. Given these features, appealing candidate pathogenicity. Understanding molecular cellular behind SARS-CoV-2-associated-lymphopenia will aid discovery potential therapeutic targets improve resilience our immune system against this rapidly evolving virus.

Language: Английский

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Early Use of Liraglutide for the Treatment of Acute COVID-19 Infection: An Open-Label Single-Center Phase II Safety Study with Biomarker Profiling

Infectious Disease Reports, Journal Year: 2025, Volume and Issue: 17(1), P. 5 - 5

Published: Jan. 10, 2025

Background: Glucagon-like peptide-1 (GLP-1) agonists are an existing treatment option for patients with insulin-resistant states, which elicit further pleiotropic effects related to immune cell recruitment and vascular inflammation. GLP-1 downregulate the cluster of differentiation 147 (CD147) receptor, one several receptors SARS-CoV-2 spike protein that mediate viral infection host cells. Methods: We conducted open-label prospective safety tolerability study including biomarker responses agonist Liraglutide, administered 5 days as add-on therapy standard care within 48 h presentation in a cohort 13 hospitalized COVID-19 pneumonia. Biomarker were compared admitted critical those not requiring admission (non-critical group). Results: Liraglutide (0.6 mg, subcutaneously) was well tolerated by all alive 30 after diagnosis. Plasma soluble CD147 levels reduced non-critical patient group at day contrast care-treated patients, who demonstrated increase between 0 5. Patients milder pneumonia severity also improvement echocardiographic parameters right left ventricular function, reduction plasma Troponin levels, increased expression on T lymphocytes, IL-8. Conclusions: This first-in-disease use demonstrates its unselected across range clinical severities.

Language: Английский

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Cyclophilin–CD147 interaction enables SARS-CoV-2 infection of human monocytes and their activation via Toll-like receptors 7 and 8

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 3, 2025

Monocytes and macrophages, as important constituents of the innate immune system, are equipped with multiple Toll-like-receptors (TLRs) to recognize invading pathogens, such SARS-CoV-2, mount an antiviral response. Nevertheless, their uncontrolled activation can lead hyperinflammation seen in severe COVID-19. Surprisingly, we observed that recombinant SARS-CoV-2 Spike (S) Nucleocapsid (N) proteins triggered only a weak proinflammatory response human peripheral blood monocytes. By employing THP-1 Jurkat NF-κB::eGFP reporter cell lines expressing specific TLRs, various TLR ligands blocking antibodies, determined surface including TLR2/1, TLR2/6 TLR4 do not play major role sensing. However, monocytes potently activated by replication-competent correlates viral uptake is monocytes, but lymphocytes. We show monocyte involves two distinct steps. Firstly, infects process independent S protein prime receptor angiotensin-converting enzyme 2. Instead, alternative CD147, which highly expressed on recognizes its well-known interaction partners cyclophilins A B incorporated into virions. Secondly, upon via cyclophilin-CD147 interaction, be inhibited CD147 antibodies or competition cyclophilin B, RNA recognized TLR7/8 endosomes, leading upregulation tumor necrosis factor (TNF), interleukin (IL)-1β IL-6, comprising core hyperinflammatory signature. Taken together, our data reveal novel mechanism how sense suggest targeting axis might beneficial alleviate overt myeloid-driven inflammation infection.

Language: Английский

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Defining diverse Spike-Receptor interactions involved in SARS-CoV-2 entry: Mechanisms and Therapeutic Opportunities

Virology, Journal Year: 2025, Volume and Issue: unknown, P. 110507 - 110507

Published: March 1, 2025

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an enveloped RNA virus that caused the Disease 2019 (COVID-19) pandemic. The SARS-CoV-2 Spike glycoprotein binds to angiotensin converting enzyme (ACE2) on host cells facilitate viral entry. However, presence of in nearly all human organs - including those with little or no ACE2 expression suggests involvement alternative receptors. Recent studies have identified several cellular proteins and molecules influence entry through ACE2-dependent, ACE2-independent, inhibitory mechanisms. In this review, we explore how these receptors were identified, their patterns roles entry, impact infection. Additionally, discuss therapeutic strategies aimed at disrupting virus-receptor interactions mitigate COVID-19 pathogenesis.

Language: Английский

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CD147 inhibition reduced fibronectin expression in TGF-β1-induced keloid fibroblasts by targeting Smad2 signaling pathway

Burns, Journal Year: 2025, Volume and Issue: unknown, P. 107472 - 107472

Published: March 1, 2025

Language: Английский

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CD147-high classical monocytes: a cellular biomarker for COVID-19 disease severity and treatment response

Inflammation and Regeneration, Journal Year: 2025, Volume and Issue: 45(1)

Published: April 7, 2025

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to severe disease 2019 (COVID-19), which is characterized by cytokine storm and organ dysfunction. The spike S1 subunit induces inflammatory production, but the immune cell subsets that respond stimulation contribute severity remain unclear. Methods We analyzed serum samples peripheral blood mononuclear cells (PBMCs) from patients with COVID-19 (moderate: n = 7; severe: 25) healthy controls ( 38). Using mass cytometry (cytometry time-of-flight; CyTOF), we responses in PBMCs donors COVID-19. examined correlations among identified populations, levels, clinical parameters. Results Serum levels correlated concentrations. induced dose-dependent production PBMCs, predominantly myeloid cells. CyTOF analysis classical monocytes high CD147 expression (CD147hi cMono) as primary source of S1-induced cytokines. proportion CD147hi cMono increased significantly decreased improvement. frequency showed a stronger positive correlation markers younger compared older patients. Conclusions are cellular cytokines may serve potential biomarkers for monitoring treatment response.

Language: Английский

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Meplazumab, a CD147 antibody, for severe COVID-19: a double-blind, randomized, placebo-controlled, phase 3 clinical trial

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: April 13, 2025

Meplazumab, a humanized CD147 antibody, showed favorable safety and clinical benefits in phase 1 2/3 seamless studies. Further evaluation of its therapeutic efficacy patients with severe COVID-19 is needed. In this 3 add-on study, we randomized 1:1 ratio to receive 0.2 mg/kg meplazumab or placebo via intravenous injection, evaluated within 56 days. Between February 2023 November 2023, 108 were two groups, their baseline characteristics generally balanced. The primary endpoint, 28-day all-cause mortality was 1.96% the group vs 7.69% (P = 0.1703). Supplementary analysis using composite strategy indicated significant reduction compared (3.92% 15.38%, P 0.044). Meplazumab also significantly reduced smoking subjects on day 28 0.047) supplementary analysis. secondary 56-day mortality, 11.54% 0.048), which 3.92% respectively 0.044) by Additional endpoints potential benefits, including increased hospital discharge rates, improved outcomes, viral nucleotide conversion rate. demonstrated good tolerability, no grade ≥ TEAEs observed. These promising results indicate that reduces enhances profile, providing effective specific therapeutics for (the trial registered at ClinicalTrials.gov (NCT05679479)).

Language: Английский

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Status and Developing Strategies for Neutralizing Monoclonal Antibody Therapy in the Omicron Era of COVID-19

Viruses, Journal Year: 2023, Volume and Issue: 15(6), P. 1297 - 1297

Published: May 31, 2023

The monoclonal antibody (mAb)-based treatment is a highly valued therapy against COVID-19, especially for individuals who may not have strong immune responses to the vaccine. However, with arrival of Omicron variant and its evolving subvariants, along occurrence remarkable resistance these SARS-CoV-2 variants neutralizing antibodies, mAbs are facing tough challenges. Future strategies developing improved viral evasion will involve optimizing targeting epitopes on SARS-CoV-2, enhancing affinity potency mAbs, exploring use non-neutralizing antibodies that bind conserved S protein, as well immunization regimens. These approaches can improve viability mAb in fight threat coronavirus.

Language: Английский

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