Repurposing niclosamide as a novel anti-SARS-Cov-2 drug by restricting entry protein CD147 DOI Creative Commons
Zhe Yang, Qi Zhang, Xiaoqing Wu

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Апрель 13, 2023

Abstract Background The burst of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the global COVID-19 pandemic. But until today only limited numbers drugs are discovered to treat patients. Even worse, rapid mutations SARS-CoV-2 compromise effectiveness existing vaccines and neutralizing antibodies due increased viral transmissibility immune escape. CD147-spike protein, one entries SRAR-CoV-2 into host cells, has been reported as a promising therapeutic target for developing against COVID-19. Methods CRISPR-Cas9 induced gene knockout, western blotting, tet-off protein overexpression, ribonucleoprotein IP RNA-IP were used confirm regulation HuR on mRNA CD147. Regulation niclosamide nucleo-translocation was assessed by immunofluorescence staining cell lines, IHC tissue mouse model blotting. Finally, suppression infection CD147 evaluated ACE2-expressing A549 cells Results We first novel mechanism via RNA-binding HuR. found that regulates post-transcription directly bound its 3'-UTR. loss reduced in multiple lines. Niclosamide inhibited function blocking cytoplasmic translocation diminishing glycosylation. which could be neutralized dose-dependent manner. Conclusion Together, our study reveals can repurposed an effective drug targeting virus entry, protein.

Язык: Английский

Animal models for COVID-19: advances, gaps and perspectives DOI Creative Commons
Changfa Fan, Yong Wu,

Rui Xiong

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июль 7, 2022

Abstract COVID-19, caused by SARS-CoV-2, is the most consequential pandemic of this century. Since outbreak in late 2019, animal models have been playing crucial roles aiding rapid development vaccines/drugs for prevention and therapy, as well understanding pathogenesis SARS-CoV-2 infection immune responses hosts. However, current some deficits there an urgent need novel to evaluate virulence variants concerns (VOC), antibody-dependent enhancement (ADE), various comorbidities COVID-19. This review summarizes clinical features COVID-19 different populations, characteristics major including those naturally susceptible animals, such non-human primates, Syrian hamster, ferret, minks, poultry, livestock, mouse sensitized genetically modified, AAV/adenoviral transduced, mouse-adapted strain engraftment human tissues or cells. host receptors proteases essential designing advanced modified models, successful studies on are also reviewed. Several improved alternatives future proposed, reselection alternative receptor genes multiple gene combinations, use transgenic knock-in method, strains establishing next generation mice.

Язык: Английский

Процитировано

81
ACE2-Independent Alternative Receptors for SARS-CoV-2 DOI Creative Commons
Suhyeon Lim, Monica Zhang, Theresa L. Chang

и другие.

Viruses, Год журнала: 2022, Номер 14(11), С. 2535 - 2535

Опубликована: Ноя. 16, 2022

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), is highly contagious and remains a major public health challenge despite availability effective vaccines. SARS-CoV-2 enters cells through binding its spike receptor-binding domain (RBD) to human angiotensin-converting enzyme 2 (ACE2) receptor in concert with accessory receptors/molecules that facilitate viral attachment, internalization, fusion. Although ACE2 plays critical role replication, expression profiles are not completely associated infection patterns, immune responses, clinical manifestations. Additionally, infects lack ACE2, resistant monoclonal antibodies against RBD vitro, indicating some possess ACE2-independent alternative receptors, which can mediate entry. Here, we discuss these receptors their interactions components for These include CD147, AXL, CD209L/L-SIGN/CLEC4M, CD209/DC-SIGN/CLEC4L, CLEC4G/LSECtin, ASGR1/CLEC4H1, LDLRAD3, TMEM30A, KREMEN1. Most known be involved entry other viruses modulate cellular functions responses. The omicron variant exhibits altered cell tropism an change pathway, emerging variants may use escape pressure ACE2-dependent provided by vaccination RBD. Understanding pathogenesis provide avenues prevention treatment COVID-19.

Язык: Английский

Процитировано

72
SARS-CoV-2 Receptors and Their Involvement in Cell Infection DOI Open Access
П. П. Авдонин,

E. Yu. Rybakova,

S. K. Trufanov

и другие.

Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology, Год журнала: 2023, Номер 17(1), С. 1 - 11

Опубликована: Март 1, 2023

Язык: Английский

Процитировано

16
Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial DOI Creative Commons
Huijie Bian, Liang Chen, Zhaohui Zheng

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Янв. 30, 2023

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled randomized to receive three dosages of meplazumab placebo. Meplazumab at 0.12 mg/kg, compared the placebo group, showed benefits significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing proportion alive discharged without supplemental oxygen (82.9% 70.7%, 0.0337) who achieved sustained improvement (41.5% 31.7%). The response rate 0.2 mg/kg group was relatively increased 16.0% (53.7% 46.3%). also reduced viral loads multiple cytokine levels. Compare 0.3 virus negative 40.6% (p 0.0363) IL-8 level 0.0460); conversion 36.9%, IL-4 0.0365) levels 0.0484). this study, adverse events occurred comparable across four groups, no unexpected findings observed. conclusion, promoted convalescence mortality, load, population good profile.

Язык: Английский

Процитировано

13
CD147-CAR-NK Cell Therapy Shows Minimal Toxicities in Human CD147 Transgenic Mouse Model with Solid Tumors DOI Creative Commons

Youssef Sabha,

Sang Hoon Kim, Tseng Hsiang-Chi

и другие.

Deleted Journal, Год журнала: 2025, Номер 33(1), С. 200957 - 200957

Опубликована: Фев. 26, 2025

The toxicity of chimeric antigen receptor-natural killer (CAR-NK) therapy has not been tested in solid tumors, compared with CAR-T side by side. To address this, we investigated the CD147-CAR-NK "on-target/off-tumor" and neurotoxicity human CD147-transgenic (hCD147TG) mice hepatocellular carcinoma (HCC). We first vitro cytotoxicity against CD147+ tumor healthy cells. Both cells CD147-IL15-CAR-NK (autocrine expressing interleukin [IL]-15) can kill specifically but lung spleen tissue from hCD147TG mice. In vivo assays show minimal systemic toxicities tissues 1-week-longer persistence times than non-tumor tissues. evaluate neurotoxicity, expression ionized calcium-binding adaptor protein 1 (IBA1), glial fibrillary acidic (GFAP), inducible nitric oxide synthase (iNOS) between CD147-CAR-T- CD147-CAR-NK-treated HCC. exhibited higher GFAP IBA1 control groups. CD147-CAR-T-treated showed an increase iNOS to behavioral studies testing spatial memory that treated exhibit better function This study provides a deeper understanding relative CD147-CAR-T therapy.

Язык: Английский

Процитировано

0
CD147-high classical monocytes: a cellular biomarker for COVID-19 disease severity and treatment response DOI Creative Commons

Teruaki Murakami,

Yuta Yamaguchi,

Saori Amiya

и другие.

Inflammation and Regeneration, Год журнала: 2025, Номер 45(1)

Опубликована: Апрель 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.

Язык: Английский

Процитировано

0
Status and Developing Strategies for Neutralizing Monoclonal Antibody Therapy in the Omicron Era of COVID-19 DOI Creative Commons

Zuning Ren,

Chenguang Shen, Jie Peng

и другие.

Viruses, Год журнала: 2023, Номер 15(6), С. 1297 - 1297

Опубликована: Май 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.

Язык: Английский

Процитировано

6
Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147 DOI Creative Commons
Zhe Yang, Qi Zhang, Xiaoqing Wu

и другие.

Biomedicines, Год журнала: 2023, Номер 11(7), С. 2019 - 2019

Опубликована: Июль 18, 2023

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the global disease 2019 (COVID-19) pandemic, and search for effective treatments been limited. Furthermore, rapid mutations SARS-CoV-2 have posed challenges existing vaccines neutralizing antibodies, as they struggle keep up with increased viral transmissibility immune evasion. However, there is hope in targeting CD147-spike protein, which serves an alternative point entry into host cells. This protein emerged a promising therapeutic target development drugs against COVID-19. Here, we demonstrate that RNA-binding Human-antigen R (HuR) plays crucial role post-transcriptional regulation CD147 by directly binding its 3'-untranslated region (UTR). We observed decrease levels across multiple cell lines upon HuR depletion. identified niclosamide can reduce lowering cytoplasmic translocation reducing glycosylation. Moreover, our investigation revealed infection induces upregulation ACE2-expressing A549 cells, be effectively neutralized dose-dependent manner. Overall, study unveils novel regulatory mechanism regulating through suggests option

Язык: Английский

Процитировано

6
COVID‐19 vaccine adverse events: Evaluating the pathophysiology with an emphasis on sulfur metabolism and endotheliopathy DOI Creative Commons
Heidi N. du Preez, Johnson Lin, Glenn E. M. Maguire

и другие.

European Journal of Clinical Investigation, Год журнала: 2024, Номер 54(10)

Опубликована: Авг. 8, 2024

Abstract In this narrative review, we assess the pathophysiology of severe adverse events that presented after vaccination with DNA and mRNA vaccines against COVID‐19. The focus is on perspective an undersulfated degraded glycocalyx, considering its impact immunomodulation, inflammatory responses, coagulation oxidative stress. paper explores various factors lead to glutathione inorganic sulfate depletion their subsequent effect glycocalyx sulfation other metabolites, including hormones. Components COVID‐19 vaccines, such as material, spike protein antigen lipid nanoparticles, are involved in possible cytotoxic effects. common thread connecting these endotheliopathy or degradation, caused by depleted levels, shear stress from circulating aggregation formation coronas; leading imbalanced immune responses chronic release pro‐inflammatory cytokines, ultimately resulting systemic response syndrome. By understanding underlying events, better treatment options can be explored.

Язык: Английский

Процитировано

1
Repurposing niclosamide as a novel anti-SARS-Cov-2 drug by restricting entry protein CD147 DOI Creative Commons
Zhe Yang, Qi Zhang, Xiaoqing Wu

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Апрель 13, 2023

Abstract Background The burst of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the global COVID-19 pandemic. But until today only limited numbers drugs are discovered to treat patients. Even worse, rapid mutations SARS-CoV-2 compromise effectiveness existing vaccines and neutralizing antibodies due increased viral transmissibility immune escape. CD147-spike protein, one entries SRAR-CoV-2 into host cells, has been reported as a promising therapeutic target for developing against COVID-19. Methods CRISPR-Cas9 induced gene knockout, western blotting, tet-off protein overexpression, ribonucleoprotein IP RNA-IP were used confirm regulation HuR on mRNA CD147. Regulation niclosamide nucleo-translocation was assessed by immunofluorescence staining cell lines, IHC tissue mouse model blotting. Finally, suppression infection CD147 evaluated ACE2-expressing A549 cells Results We first novel mechanism via RNA-binding HuR. found that regulates post-transcription directly bound its 3'-UTR. loss reduced in multiple lines. Niclosamide inhibited function blocking cytoplasmic translocation diminishing glycosylation. which could be neutralized dose-dependent manner. Conclusion Together, our study reveals can repurposed an effective drug targeting virus entry, protein.

Язык: Английский

Процитировано

2