Study identifies three novel binding receptors for SARS-CoV-2

A team of scientists from the United Kingdom recently conducted a large-scale screening of several membrane-bound and soluble host cell receptors to identify novel binding partners for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They have identified three novel receptors expressed on the human cell membrane; of which, one binds to SARS-CoV-2 spike with similar affinity as angiotensin-converting enzyme 2 (ACE2). The study is currently available on the bioRxiv* preprint server.

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen for coronavirus disease 2019 (COVID-19), is a single-stranded, positive-sense RNA virus with a genome size of around 30 kb. There are genetic sequence similarities between SARS-CoV-2 and other lethal members of the human beta-coronavirus family, such as SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Regarding the mode of viral entry, it is now well-established that the interaction between SARS-CoV-2 spike protein and host cell ACE2 receptor is the key step to initiate viral infection. In addition to ACE2, the host cell protease TMPRSS2 plays a pivotal role in proteolytically activate the spike protein and initiate virus envelop – host cell membrane fusion. Furthermore, a growing-pool of evidence highlights the presence of other membrane-bound or soluble human receptors/coreceptors, such as neuropilin-1 and basigin, which may facilitate the entry of SARS-CoV-2 into host cells.

In the current study, the scientists have conducted a large-scale screening of several human receptors to identify novel interactive partners for SARS-CoV-2. Specifically, they have screened a library of more than 8,500 membrane-bound and soluble receptors recombinantly expressed in human cells. To conduct binding experiments, they have also expressed and purified recombinant trimeric spike protein of SARS-CoV-2.    

Important observations

Using cell microarray approaches, the scientists identified a total of 23 binding proteins for SARS-CoV-2 full-length spike protein. Of these proteins, 15 were cell membrane receptors, and 8 were cell surface-anchored secreted proteins. For further confirmation, they conducted a series of cell microarray experiments, which led to the identification of 10 proteins specific to SARS-CoV-2 spike protein. Of these 10 proteins, 5 also interacted with the SARS-CoV spike protein and 2 interacted with the MERS-CoV spike protein. The remaining three proteins, namely NID1, CNTN1, and APOA4, interacted exclusively with the SARS-CoV-2 spike protein. Besides the identification of three novel binding proteins, the microarray experiments successfully replicated the previously-recognized interactions of SARS-CoV-2 spike protein with host cell receptors, such as ACE2, CD209, and CLEC4M.

For further validation, the scientists tested the interaction dynamics of microarray-identified proteins via flow cytometry, using spike-expressing human cells. The findings confirmed the specific interactions of all identified proteins with the SARS-CoV-2 spike protein. Similar to the microarray findings, the flow cytometric results revealed exclusive interactions between SARS-CoV-2 spike protein and host cell NID1, CNTN1, and APOA4 proteins. Importantly, the findings revealed that APOA4 interacted with the spike protein with a similar affinity as ACE2.

Study significance

The study identifies three novel binding receptors, namely NID1, CNTN1, and APOA4 for SARS-CoV-2, with APOA4 having a similar binding affinity for the spike protein as ACE2.

APOA4 is a lipoprotein expressed in the intestinal enterocytes and plays an important role in lipid metabolism. The protein is also known to facilitate the entry of hepatitis C virus into the host cells. Since 30% of COVID-19 patients present with gastrointestinal complications, the scientists suggest that APOA4 may serve as a potential intestinal entry point for SARS-CoV-2.

Of the other two novel receptors, NID1 is a basement membrane glycoprotein tightly associated with laminin and collagen networks. The protein is known to play a crucial role in the cell-extracellular matrix interaction. Similarly, CNTN1 is a neuronal membrane adhesion protein that facilitates the formation of a neuronal network.

Furthermore, the study identifies a panel of binding receptors belonging to the C-Type Lectin Domain Family 4 (CLEC4), which are known to have high affinity for glycoproteins present on the viral envelop, and thus, may influence the transmission of SARS-CoV-2.  

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Dutta, Sanchari Sinha. (2021, March 12). Study identifies three novel binding receptors for SARS-CoV-2. News-Medical. Retrieved on May 14, 2021 from https://www.news-medical.net/news/20210312/Study-identifies-three-novel-binding-receptors-for-SARS-CoV-2.aspx.

  • MLA

    Dutta, Sanchari Sinha. "Study identifies three novel binding receptors for SARS-CoV-2". News-Medical. 14 May 2021. <https://www.news-medical.net/news/20210312/Study-identifies-three-novel-binding-receptors-for-SARS-CoV-2.aspx>.

  • Chicago

    Dutta, Sanchari Sinha. "Study identifies three novel binding receptors for SARS-CoV-2". News-Medical. https://www.news-medical.net/news/20210312/Study-identifies-three-novel-binding-receptors-for-SARS-CoV-2.aspx. (accessed May 14, 2021).

  • Harvard

    Dutta, Sanchari Sinha. 2021. Study identifies three novel binding receptors for SARS-CoV-2. News-Medical, viewed 14 May 2021, https://www.news-medical.net/news/20210312/Study-identifies-three-novel-binding-receptors-for-SARS-CoV-2.aspx.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
You might also like... ×
Researchers show SARS-CoV-2 genes can be integrated into the human genome