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

Shilts, Jarrod; Wright, Gavin J.

doi:10.1101/2020.07.25.221036

Cited by 48 publications

(49 citation statements)

References 55 publications

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“…Due to the abundance of DPP4 in astrocytes prior to infection, and recent findings suggesting BSG/CD147 may not directly bind SARS-CoV-2 ( 32 ), we focused our attention on whether DPP4 could mediate cortical astrocyte tropism. Organotypic slice cultures were treated with the DPP4 inhibitor, Vildagliptin, for 24 hours prior to and throughout the duration of infection.…”

Section: Resultsmentioning

confidence: 99%

Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes

Andrews

Mukhtar

Eze

et al. 2021

Preprint

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. It proves fatal for one percent of those infected. Neurological symptoms, which range in severity, accompany a significant proportion of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized primary human cortical tissue and stem cell-derived cortical organoids. We find significant and predominant infection in cortical astrocytes in both primary and organoid cultures, with minimal infection of other cortical populations. Infected astrocytes had a corresponding increase in reactivity characteristics, growth factor signaling, and cellular stress. Although human cortical cells, including astrocytes, have minimal ACE2 expression, we find high levels of alternative coronavirus receptors in infected astrocytes, including DPP4 and CD147. Inhibition of DPP4 reduced infection and decreased expression of the cell stress marker, ARCN1. We find tropism of SARS-CoV-2 for human astrocytes mediated by DPP4, resulting in reactive gliosis-type injury.

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Section: Resultsmentioning

confidence: 99%

Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes

Andrews

Mukhtar

Eze

et al. 2021

Preprint

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“…Basigin has been proposed as an alternative receptor for SARS-CoV-2 S protein ( 112 ), although other authors have failed to detect interactions between the viral protein and human basigin ( 113 ). By contrast to ACE2, basigin is ubiquitously expressed at high levels, most notably in the heart.…”

Section: Several Membrane-associated Serine Proteinases Might Synergimentioning

confidence: 99%

Priming of SARS-CoV-2 S protein by several membrane-bound serine proteinases could explain enhanced viral infectivity and systemic COVID-19 infection

Fuentes‐Prior

2021

Journal of Biological Chemistry

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The ongoing COVID-19 pandemic has already caused over a million deaths worldwide, and this death toll will be much higher before effective treatments and vaccines are available. The causative agent of the disease, the coronavirus SARS-CoV-2, shows important similarities with the previously emerged SARS-CoV-1, but also striking differences. First, SARS-CoV-2 possesses a significantly higher transmission rate and infectivity than SARS-CoV-1 and has infected in a few months over 60 million people. Moreover, COVID-19 has a systemic character, as in addition to the lungs it also affects heart, liver, and kidneys among other organs of the patients, and causes frequent thrombotic and neurological complications. In fact, the term “viral sepsis” has been recently coined to describe the clinical observations. Here I review current structure-function information on the viral spike proteins and the membrane fusion process to provide plausible explanations for these observations. I hypothesize that several membrane-associated serine proteinases (MASPs), in synergy with or in place of TMPRSS2, contribute to activate the SARS-CoV-2 spike protein. Relative concentrations of the attachment receptor, ACE2, MASPs, their endogenous inhibitors (the Kunitz-type transmembrane inhibitors, HAI-1/SPINT1 and HAI-2/SPINT2, as well as major circulating serpins) would determine the infection rate of host cells. The exclusive or predominant expression of major MASPs in specific human organs suggests a direct role of these proteinases in e.g. heart infection and myocardial injury, liver dysfunction, kidney damage, as well as neurological complications. Thorough consideration of these factors could have a positive impact on the control of the current COVID-19 pandemic.

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“…This protein is utilized by the parasite Plasmodium falciparum , which causes malaria in humans ( Crosnier et al., 2011 ), and a few studies demonstrated that it serves as an alternative receptor that can be bound by SARS-CoV ( De Wit et al., 2016 ). Whether CD147 also plays a role in SARS-CoV-2 entry is unclear, with one preprint study demonstrating that it could be bound by SARS-CoV-2 ( Wang et al., 2020b ), while a second report failed to show interaction of the virus S protein with CD147 expressed on human cells ( Shilts and Wright, 2020 ). Thus, the role of CD147, as well as its possible therapeutic impact, requires further validation, with hPSC-derived cell types potentially facilitating this effort.…”

Section: Main Textmentioning

confidence: 99%

Using Cardiovascular Cells from Human Pluripotent Stem Cells for COVID-19 Research: Why the Heart Fails

Yiangou¹,

Davis²,

Mummery³

2021

Stem Cell Reports

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the coronavirus disease (COVID-19) outbreak that became a pandemic in 2020, causing more than 30 million infections and 1 million deaths to date. As the scientific community has looked for vaccines and drugs to treat or eliminate the virus, unexpected features of the disease have emerged. Apart from respiratory complications, cardiovascular disease has emerged as a major indicator of poor prognosis in COVID-19. It has therefore become of utmost importance to understand how SARS-CoV-2 damages the heart. Human pluripotent stem cell (hPSC) cardiovascular derivatives were rapidly recognized as an invaluable tool to address this, not least because one of the major receptors for the virus is not recognized by SARS-CoV-2 in mice. Here, we outline how hPSC-derived cardiovascular cells have been utilized to study COVID-19, and their potential for further understanding the cardiac pathology and in therapeutic development.

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

Cited by 48 publications

References 55 publications

Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes

Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes

Priming of SARS-CoV-2 S protein by several membrane-bound serine proteinases could explain enhanced viral infectivity and systemic COVID-19 infection

Using Cardiovascular Cells from Human Pluripotent Stem Cells for COVID-19 Research: Why the Heart Fails

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