Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum

Zhang, Mengyao; Zhang, Yang; Wu, Xiaodong; Zhang, Kun; Peng, Lin; Bian, Huijie; Qin, Min; Huang, Wan; Ding, Wei; Zhang, Zhao; Wu, Jiao; Chen, Ruo; Fěng, Fang; Wang, Bin; Nan, Gang; Zhu, Ping; Chen, Zhi‐Nan

doi:10.1182/blood-2017-08-802918

Cited by 42 publications

(52 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, similarly with what has been shown in SARS‐CoV, another receptor‐CD147, called also basigin (encoded by BSG ), has been recently shown to act as a receptor for SARS‐CoV‐2 in cell lines of epithelial origin 9 . Interestingly, the same receptor is a putative receptor not only for SARS‐CoV, but also for HIV‐1 and measles, as well as for malaria merozoites entry to erythrocytes 10‐13 . An anti‐CD147 antibody that blocks infection with SARS‐CoV‐2 in vitro and its humanized drug (meplazumab) has been already used in a clinical trial in patients with COVID‐19 pneumonia.…”

Section: Introductionmentioning

confidence: 69%

Distribution of ACE2, CD147, CD26, and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors

Radzikowska

Ding

Tan

et al. 2020

Allergy

454

512

View full text Add to dashboard Cite

Background Morbidity and mortality from COVID‐19 caused by novel coronavirus SARS‐CoV‐2 is accelerating worldwide, and novel clinical presentations of COVID‐19 are often reported. The range of human cells and tissues targeted by SARS‐CoV‐2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS‐CoV‐2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID‐19. Methods We performed RNA sequencing and explored available RNA‐Seq databases to study gene expression and co‐expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells, and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID‐19 risk factor status. Results ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells. We also observed a distinct age‐related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2‐ and CD147‐related genes in the bronchial biopsy, BAL, or blood. Additionally, CD147‐related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of CD147‐related genes in the lesional skin of patients with atopic dermatitis. Conclusions Our data suggest different receptor repertoire potentially involved in the SARS‐CoV‐2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID‐19 morbidity and severity patterns.

show abstract

Section: Introductionmentioning

confidence: 69%

Distribution of ACE2, CD147, CD26, and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors

Radzikowska

Ding

Tan

et al. 2020

Allergy

454

512

View full text Add to dashboard Cite

show abstract

“…This soluble PfRH5-PfRipr-PfCyRPA invasion complex is required for triggering Ca 2+ release and establishing the tight junction ( Volz et al., 2016 ), with the PfP113 surface protein binding the N terminus of PfRH5 to provide an anchor to the merozoite surface ( Galaway et al., 2017 ). Further complexities surrounding PfRH5 biology have also been described, such as interactions between cyclophilin B and basigin as well as PfRhopH3 and PfRH5 ( Prakash et al., 2017 ), or PfRAP2 and basigin ( Zhang et al., 2018b ). Importantly, targeting these multiple components may improve vaccine potency; indeed antibodies against PfRH5 and PfCyRPA can synergize ( Reddy et al., 2015 ), with recent structural analyses identifying inhibitory epitopes on PfCyRPA ( Chen et al., 2017 ).…”

Section: Main Textmentioning

confidence: 99%

Malaria Vaccines: Recent Advances and New Horizons

Draper

Sack

King

et al. 2018

Cell Host & Microbe

261

249

View full text Add to dashboard Cite

The development of highly effective and durable vaccines against the human malaria parasites Plasmodium falciparum and P. vivax remains a key priority. Decades of endeavor have taught that achieving this goal will be challenging; however, recent innovation in malaria vaccine research and a diverse pipeline of novel vaccine candidates for clinical assessment provides optimism. With first-generation pre-erythrocytic vaccines aiming for licensure in the coming years, it is important to reflect on how next-generation approaches can improve on their success. Here we review the latest vaccine approaches that seek to prevent malaria infection, disease, and transmission and highlight some of the major underlying immunological and molecular mechanisms of protection. The synthesis of rational antigen selection, immunogen design, and immunization strategies to induce quantitatively and qualitatively improved immune effector mechanisms offers promise for achieving sustained high-level protection.

show abstract

“…CD147, also known as Basigin or EMMPRIN, is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily [9], which is involved in tumor development, plasmodium invasion and virus infection [10][11][12][13][14][15][16]. Our previous researches show that CD147 plays a functional role in facilitating SARS-CoV invasion for host cells, and CD147-antagonistic peptide-9 has a high binding rate to HEK293 cells and an inhibitory effect on SARS-CoV [16].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 invades host cells via a novel route: CD147-spike protein

Wang

Chen²,

Zhou³

et al. 2020

Preprint

Self Cite

621

661

View full text Add to dashboard Cite

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion.Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC 50 of 24.86 μg/mL and IC 50 of 15.16 μg/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85×10 -7 M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.

show abstract

Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum

Cited by 42 publications

References 47 publications

Distribution of ACE2, CD147, CD26, and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors

Distribution of ACE2, CD147, CD26, and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors

Malaria Vaccines: Recent Advances and New Horizons

SARS-CoV-2 invades host cells via a novel route: CD147-spike protein

Contact Info

Product

Resources

About