No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

Shilts, Jarrod; Crozier, Thomas W. M.; Greenwood, Edward Jd; Lehner, Paul J.; Wright, Gavin J.

doi:10.1038/s41598-020-80464-1

Cited by 156 publications

(143 citation statements)

References 66 publications

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“…Other co-receptors including neuropilin-1 (NRP1) have also recently been shown to bind furin-cleaved substrates and increase SARS-CoV-2 infectivity [ 16 ]. Cluster of differentiation (CD)147 (basigin) has similarly been shown to bind SARS-CoV-2 spike protein, but a role in SARS-CoV-2 infection has not been demonstrated [ 17 ]. The regulation of these receptors in COPD and potential role in susceptibility to worse COVID-19 outcomes, is not yet understood.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of COVID-19 related gene expression in the COPD lung

et al. 2021

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Background Chronic obstructive pulmonary disease (COPD) patients are at increased risk of poor outcome from Coronavirus disease (COVID-19). Early data suggest elevated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) receptor angiotensin converting enzyme 2 (ACE2) expression, but relationships to disease phenotype and downstream regulators of inflammation in the Renin-Angiotensin system (RAS) are unknown. We aimed to determine the relationship between RAS gene expression relevant to SARS-CoV-2 infection in the lung with disease characteristics in COPD, and the regulation of newly identified SARS-CoV-2 receptors and spike-cleaving proteases, important for SARS-CoV-2 infection. Methods We quantified gene expression using RNA sequencing of epithelial brushings and bronchial biopsies from 31 COPD and 37 control subjects. Results ACE2 gene expression (log2-fold change (FC)) was increased in COPD compared to ex-smoking (HV-ES) controls in epithelial brushings (0.25, p = 0.042) and bronchial biopsies (0.23, p = 0.050), and correlated with worse lung function (r = − 0.28, p = 0.0090). ACE2 was further increased in frequent exacerbators compared to infrequent exacerbators (0.51, p = 0.00045) and associated with use of ACE inhibitors (ACEi) (0.50, p = 0.0034), having cardiovascular disease (0.23, p = 0.048) or hypertension (0.34, p = 0.0089), and inhaled corticosteroid use in COPD subjects in bronchial biopsies (0.33, p = 0.049). Angiotensin II receptor type (AGTR)1 and 2 expression was decreased in COPD bronchial biopsies compared to HV-ES controls with log2FC of –0.26 (p = 0.033) and − 0.40, (p = 0.0010), respectively. However, the AGTR1:2 ratio was increased in COPD subjects compared with HV-ES controls, log2FC of 0.57 (p = 0.0051). Basigin, a newly identified potential SARS-CoV-2 receptor was also upregulated in both brushes, log2FC of 0.17 (p = 0.0040), and bronchial biopsies, (log2FC of 0.18 (p = 0.017), in COPD vs HV-ES. Transmembrane protease, serine (TMPRSS)2 was not differentially regulated between control and COPD. However, various other spike-cleaving proteases were, including TMPRSS4 and Cathepsin B, in both epithelial brushes (log2FC of 0.25 (p = 0.0012) and log2FC of 0.56 (p = 5.49E−06), respectively) and bronchial biopsies (log2FC of 0.49 (p = 0.00021) and log2FC of 0.246 (p = 0.028), respectively). Conclusion This study identifies key differences in expression of genes related to susceptibility and aetiology of COVID-19 within the COPD lung. Further studies to understand the impact on clinical course of disease are now required.

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Section: Introductionmentioning

confidence: 99%

Dysregulation of COVID-19 related gene expression in the COPD lung

et al. 2021

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“…Moreover, an electron microscope demonstrated virions in Vero E6 cells, lung, and kidney tissues. In contrast, Shilts et al [ 56 ] indicated that the recombinant forms of the SARS-CoV-2 spike do not interact with CD147 expressed on the surface of human cells. These reports question the role of this receptor in the pathogenesis of SARS-CoV-2.…”

Section: Receptors For Sars-cov-2 Entry and Replication Cyclementioning

confidence: 98%

SARS-CoV-2—Morphology, Transmission and Diagnosis during Pandemic, Review with Element of Meta-Analysis

Grudlewska‐Buda

Wiktorczyk-Kapischke

Wałecka-Zacharska

et al. 2021

JCM

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The outbreak of Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2). Thus far, the virus has killed over 2,782,112 people and infected over 126,842,694 in the world (state 27 March 2021), resulting in a pandemic for humans. Based on the present data, SARS-CoV-2 transmission from animals to humans cannot be excluded. If mutations allowing breaking of the species barrier and enhancing transmissibility occurred, next changes in the SARS-CoV-2 genome, leading to easier spreading and greater pathogenicity, could happen. The environment and saliva might play an important role in virus transmission. Therefore, there is a need for strict regimes in terms of personal hygiene, including hand washing and surface disinfection. The presence of viral RNA is not an equivalent of active viral infection. The positive result of the RT-PCR method may represent either viral residues or infectious virus particles. RNA-based tests should not be used in patients after the decline of disease symptoms to confirm convalescence. It has been proposed to use the test based on viral, sub-genomic mRNA, or serological methods to find the immune response to infection. Vertical transmission of SARS-CoV-2 is still a little-known issue. In our review, we have prepared a meta-analysis of the transmission of SARS-CoV-2 from mother to child depending on the type of delivery. Our study indicated that the transmission of the virus from mother to child is rare, and the infection rate is not higher in the case of natural childbirth, breastfeeding, or contact with the mother. We hope that this review and meta-analysis will help to systemize knowledge about SARS-CoV-2 with an emphasis on diagnostic implications and transmission routes, in particular, mother-to-child transmission.

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“…Surprisingly, ACE2 expression was not detected in the frequently studied lung epithelial cell line A549 [ 42 ]. Although there has been significant work on ACE2, controversial reports were also published on ACE2-independent viral entry using CD147/basigin [ 44 , 45 ]. Primary cultures of alveolar type II cells were used in early studies of epithelial ion transport [ 46 ].…”

Section: Modeling Lung Pathologymentioning

confidence: 99%

Application of lung microphysiological systems to COVID-19 modeling and drug discovery: a review

et al. 2021

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There is a pressing need for effective therapeutics for coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The process of drug development is a costly and meticulously paced process, where progress is often hindered by the failure of initially promising leads. To aid this challenge, in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening, thereby saving valuable time and resources during a pandemic crisis. The SARS-CoV-2 virus attacks the lung, an organ where the unique three-dimensional (3D) structure of its functional units is critical for proper respiratory function. The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types. Current model systems include Transwell, organoid and organ-on-a-chip or microphysiological systems (MPSs). We review models that have direct relevance toward modeling the pathology of COVID-19, including the processes of inflammation, edema, coagulation, as well as lung immune function. We also consider the practical issues that may influence the design and fabrication of MPS. The role of lung MPS is addressed in the context of multi-organ models, and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.

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No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

Cited by 156 publications

References 66 publications

Dysregulation of COVID-19 related gene expression in the COPD lung

Dysregulation of COVID-19 related gene expression in the COPD lung

SARS-CoV-2—Morphology, Transmission and Diagnosis during Pandemic, Review with Element of Meta-Analysis

Application of lung microphysiological systems to COVID-19 modeling and drug discovery: a review

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