For the best experience on the Abcam website please upgrade to a modern browser such as Google Chrome

Hello. We're improving abcam.com and we'd welcome your feedback.

Hello. We're improving abcam.com and we'd welcome your feedback.

Infomation icon

We haven't added this to the BETA yet

New BETA website

New BETA website

Hello. We're improving abcam.com and we'd welcome your feedback.

Take a look at our BETA site and see what we’ve done so far.

Switch on our new BETA site

Now available

Search and browse selected products

  • A selection of primary antibodies

Purchase these through your usual distributor

In the coming months

  • Additional product types
  • Supporting content
  • Sign in to your account
  • Purchase online
United States
Your country/region is currently set to:

If incorrect, please enter your country/region into the box below, to view site information related to your country/region.

Call (888) 77-ABCAM (22226) or contact us
Need help? Contact us

  • My account
  • Sign out
Sign in or Register with us

Welcome

Sign in or

Don't have an account?

Register with us
My basket
Quick order
Abcam homepage

  • Research Products
    By product type
    Primary antibodies
    Secondary antibodies
    ELISA and Matched Antibody Pair Kits
    Cell and tissue imaging tools
    Cellular and biochemical assays
    By product type
    Proteins and Peptides
    Proteomics tools
    Agonists, activators, antagonists and inhibitors
    Cell lines and Lysates
    Multiplex Assays
    By research area
    Cancer
    Cardiovascular
    Cell Biology
    Epigenetics
    Metabolism
    Developmental Biology
    By research area
    Immunology
    Microbiology
    Neuroscience
    Signal Transduction
    Stem Cells
  • Customized Products & Partnerships
    Customized Products & Partnerships

    Customized products and commercial partnerships to accelerate your diagnostic and therapeutic programs.

    Customized products

    Partner with us

  • Support
    Support hub

    Access advice and support for any research roadblock

    View support hub

    Protocols

    Your experiments laid out step by step

    View protocols

  • Events
    • Conference calendar
    • Cancer
    • Cardiovascular
    • Epigenetics & Nuclear signaling
    • Immunology
    • Neuroscience
    • Stem cells
    • Tradeshows
    • Scientific webinars
    Keep up to date with the latest events

    Full event breakdown with abstracts, speakers, registration and more

    View global event calendar

  • Pathways
    Cell signalling pathways

    View all pathways

    View all interactive pathways

SARS-CoV-2 virus

Structural and functional mechanism of SARS-CoV-2 cell entry

Related

  • Supporting our customers during COVID-19
    • COVID-19 research information and products
      • Information and products associated with cytokine storm in COVID-19 research
        • Curated COVID-19 resources
          • Our China team's emergence from COVID-19
            • Blood-based biomarkers for COVID-19
              • Our scientists’ tips for resuming research post-COVID-19
                • SARS-CoV-2 spike protein antibodies in action
                  • Maximize research efficiency on return to the lab
                    • Quality recombinant SARS-CoV-2 proteins
                      • SARS-CoV-2 infection serology
                        • Cell engineering products for COVID-19

                          The novel coronavirus, SARS-CoV-2, is thought to have emerged in China in 2019 and has since spread across the globe, causing a global pandemic. Understanding the structure and function of SARS-CoV-2 and its variants is essential in developing vaccines and therapies to tackle the COVID-19 disease.

                          Updated May 19, 2022

                          Overview

                          • SARS-CoV-2 virus
                          • SARS-CoV-2 binding to cell receptor
                          • Alternative SARS-CoV-2 cell entry mechanisms
                          • SARS-CoV-2 related products

                            

                          SARS-CoV-2 virus

                          Early genomic analysis of SARS-CoV-2  revealed that it belongs to the betacoronavirus genus, lineage B, alongside SARS-CoV-21,2. Coronaviruses are enveloped, single-strand RNA viruses characterized by club-like spikes projecting from their surface and an unusually large RNA genome3. The SARS-CoV-2 genome encodes four major structural proteins: the spike (S) protein, nucleocapsid (N) protein, membrane (M) protein and the envelope (E) protein, each of which is essential to compose the viral particle 3.  


                          Binding of SARS-CoV-2 to the host cell receptor

                          ​Like all coronaviruses, SARS-CoV-2 utilizes the S glycoprotein to mediate entry into the host cell. This protein contains two subunits: the S1 subunit that contains the receptor-binding domain (RBD) and N-terminal domain (NTD), and a second S2 subunit that mediates the fusion of the viral and host cell membranes4.​

                          SARS-CoV-2 S protein binds to the ACE2 receptor at the surface of host cells, initially through the S1 RBD. S1 is then shed from the viral surface, allowing S2 to fuse to the host cell membrane. This process is dependent upon activation of the S protein, by cleavage at two sites (S1/S2 and S2’) via the proteases Furin and TMPRSS2. Furin cleavage at the S1/S2 site may lead to conformational changes in the viral S protein that exposes the RBD and/or the S2 domain. TMPRSS2 cleavage of the SARS-CoV-2 S protein is believed to enable the fusion of the viral capsid with the host cell to permit viral entry5,6. 

                          ​​

                          Exposure of the RBD in the S1 protein subunit creates an unstable subunit conformation. Consequently, during binding, S1 undergoes conformational rearrangement between two states, known as the up and down conformations. The down state transiently hides the RBD, while the up state exposes the RBD, but temporarily destabilizes the protein subunit7,8,9. Within the trimeric S protein, only one of the three RBD heads is present in the accessible conformation to bind the human Angiotensin 2 (hACE2) host cell receptor10.

                          Many of the mutations found in SARS-CoV-2 variants of concern (VoCs) are found in the S gene – most commonly within the S1/RBD regions. Many such mutations have been shown to improve affinity S1’s for ACE2 and promote RBD flexibility and cleavage efficiency to enhance infection11. Unlike previous variants, however, Omicron shows reduced cleavage efficiency as well as impaired cell entry in the presence of TMPRSS212. The reason for this is thought to be Omicron’s greater reliance on the endosomal pathway.

                          Alternative SARS-CoV-2 cell entry mechanisms

                          In addition to binding ACE2, increasing evidence suggests that SARS-CoV-2 can also bind other surface proteins to gain cell entry. Indeed, the increased transmissibility of SARS-CoV-2 compared with SARS-CoV could potentially be explained by an increased number of cellular receptors allowing the virus to penetrate host cells.

                          Both Neuropilin-1 and Neuropilin-2 have been shown to bind the cleaved form of the SARS-CoV-2 S protein to mediate host cell entry 13, 14.  Neuropilin proteins are expressed in neurons, providing an entry system for the virus into the nervous system and this has been observed in the neuropathological analysis of human COVID-19 autopsies 14. Antibody blockade of the NP receptors, receptor mutagenesis and structural studies all support the role of NP as a cell receptor for SARS-CoV-2 S protein 13, 14. Binding to NP receptors on the cell surface, in addition to the known ACE2 receptor, was shown to potentiate SARS-CoV-2 infection and may explain the increased tissue tropism seen in SARS-CoV-2 infection, compared to SARS-CoV 13, 14.

                          An initial study suggested that the SARS-CoV-2 S protein was able to bind to CD147 on the cell surface and subsequently enter the cell 15. As part of this study, in vitro antiviral tests indicated that meplazumab, an anti-CD147 humanized antibody that blocks the interaction of the S protein with the CD147 cell surface receptor, significantly inhibited viral cell entry. Clinical trials into the potential of this antibody to treat COVID-19 are ongoing 16. As higher blood sugar levels are known to upregulate CD147 expression, this could help to explain why diabetes is a factor for poor prognosis in cases of COVID-19 17.

                          Frequent cellular targets of the SARS-CoV-2 virus within the human host are neuronal cells, the endothelial cells of blood vessels, and epithelial cells within the respiratory system and gastrointestinal tract 18. However, ACE2 is known to be expressed only at low levels within the brain 19. A structural modeling study indicated that SARS-CoV-2 can bind to sialic acid glycoproteins and gangliosides on the cell surface20, and sialic acid is known to be expressed at high levels on the surface of all of the cell types targeted by SARS-CoV-2 21, including neuronal cells. This is a common cell entry mechanism for other viruses, including influenza 22, MERS, SARS-CoV and HCoV-OC43 23, and could offer potential new therapeutic strategies using drugs to lower sialic acid levels in COVID-19 patients to help prevent SARS-CoV-2 cell entry 24. 

                          In addition to these factors, a range of alternative entry receptors have been associated with SARS-CoV-2 cell entry, including C-type lectins, DC-SIGN, L-SIGN, AXL and TIM125.

                          SARS-CoV-2 recommended products

                          Zhou P, Yang XL, Wang XG, et al.  A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020). 
                          Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature 579, 265–269 (2020). 
                          Fehr AR and Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 1282:1-23 (2015).
                          Walls AC, Park YJ, Tortorici MA, et al. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 181(2), 281-292.e6 (2020).
                          Bestle D, Heindl MR, Limbu H et al. TMPRSS2 and furin are both essential for proteolytic activation and spread of SARS-CoV-2 in human airway epithelial cells and provide promising drug targets. bioRxiv doi: https://doi.org/10.1101/2020.04.15.042085 (2020). 
                          Yuan M, Wu MC, Zhu X, et al. A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV. Science 10.1126/science.abb7269 (2020).
                          Gui M, Song W, Zhou H, et al. Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell Res. 27, 119–129 (2017).
                          Walls AC, Xiong X, Park YJ, et al. Unexpected receptor functional mimicry elucidates activation of coronavirus fusion. Cell 176, 1026–1039.e15 (2019).
                          Walls AC, Tortorici MA, Snijder J, et al. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc. Natl. Acad. Sci. U.S.A. 114, 11157–11162 (2017).
                          Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 36(6483), 1260-1263 (2020).
                          Explore all SARS-CoV-2 products

                          Abcam’s products are intended for research use only, not for use in diagnostic, therapeutic or any other purposes.

                          References

                          1. ​Zhou P, Yang XL, Wang XG, et al.  A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020). 
                          2. Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature 579, 265–269 (2020). 
                          3. Fehr AR and Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 1282:1-23 (2015).
                          4. Walls AC, Park YJ, Tortorici MA, et al. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 181(2), 281-292.e6 (2020).
                          5. Bestle D, Heindl MR, Limbu H et al. TMPRSS2 and furin are both essential for proteolytic activation and spread of SARS-CoV-2 in human airway epithelial cells and provide promising drug targets. bioRxiv doi: https://doi.org/10.1101/2020.04.15.042085 (2020). 
                          6. Yuan M, Wu MC, Zhu X, et al. A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV. Science 10.1126/science.abb7269 (2020).
                          7. Gui M, Song W, Zhou H, et al. Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell Res. 27, 119–129 (2017).
                          8. Walls AC, Xiong X, Park YJ, et al. Unexpected receptor functional mimicry elucidates activation of coronavirus fusion. Cell 176, 1026–1039.e15 (2019).
                          9. Walls AC, Tortorici MA, Snijder J, et al. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc. Natl. Acad. Sci. U.S.A. 114, 11157–11162 (2017).
                          10. Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 36(6483), 1260-1263 (2020).
                          11. Harvey, TH., Carabelli, AM., Jackson, B. et al. SARS-CoV-2 variants, spike mutations and immune escape. Nature Reviews Microbiology 19,409-424 (2021). 
                          12. Hui, KPY., Ho, JCW., Cheung, M-C. et al. SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo. Nature 603, 715-720 (2022). 
                          13. Daly et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection. bioRxiv doi:10.1101/2020.06.05.134114
                          14. Cantuti-Castelvetri et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system. bioRxiv. doi:10.1101/2020.06.07.137802
                          15. Wang et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. bioRxiv. [doi:10.1101/2020.03.14988345]
                          16. Clinicaltrials.gov Clinical Study of Anti-CD147 Humanized Meplazumab for Injection to Treat With 2019-nCoV Pneumonia [Accessed: 21/07/2020]
                          17. Bao et al. Monocyte CD147 is induced by advanced glycation end products and high glucose concentration: possible role in diabetic complications. Am J Physiol Cell Physiol 299(5):C1212-9. (2010).
                          18. Zhang et al. New understanding of the damage of SARS-CoV-2 infection outside the respiratory system. Biomed Pharmacother. 127: 110195 (2020).
                          19. Alenina M and Bader M. ACE2 in Brain Physiology and Pathophysiology: Evidence from Transgenic Animal Models. Neurochem Res 44(6):1323-1329 (2019).
                          20. Fantini et al. Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int J Antimicorb Agents 55(5):105960 (2020).
                          21. Roe K. High COVID‐19 virus replication rates, the creation of antigen–antibody immune complexes and indirect haemagglutination resulting in thrombosis. Transbound Emerg Dis.  67(4):1418-1421 (2020).
                          22. Yang et al. Mutations during the Adaptation of H9N2 Avian Influenza Virus to the Respiratory Epithelium of Pigs Enhance Sialic Acid Binding Activity and Virulence in Mice. J Virol. 91(8): e02125-16 (2017).
                          23. Devaux et al. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicorb Agents 55(5):105938 (2020).
                          24. Li et al. Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein. PNAS. 114(40) E8508-E8517 (2017).
                          25. Jackson, DB., Farzan, M., Chen, B., Choe, H. Mechanisms of SARS-CoV-2 cell entry into cells. Nature Reviews Molecular Cell Biology 23, 3-20 (2022). 



                          Get resources and offers direct to your inbox Sign up
                          A-Z by research area
                          • Cancer
                          • Cardiovascular
                          • Cell biology
                          • Developmental biology
                          • Epigenetics & Nuclear signaling
                          • Immunology
                          • Metabolism
                          • Microbiology
                          • Neuroscience
                          • Signal transduction
                          • Stem cells
                          A-Z by product type
                          • Primary antibodies
                          • Secondary antibodies
                          • Biochemicals
                          • Isotype controls
                          • Flow cytometry multi-color selector
                          • Kits
                          • Loading controls
                          • Lysates
                          • Peptides
                          • Proteins
                          • Slides
                          • Tags and cell markers
                          • Tools & Reagents
                          Help & support
                          • Support
                          • Make an Inquiry
                          • Protocols & troubleshooting
                          • Placing an order
                          • RabMAb products
                          • Biochemical product FAQs
                          • Training
                          • Browse by Target
                          Company
                          • Corporate site
                          • Investor relations
                          • Company news
                          • Careers
                          • About us
                          • Blog
                          Events
                          • Tradeshows
                          • Conferences
                          International websites
                          • abcam.cn
                          • abcam.co.jp

                          Join with us

                          • LinkedIn
                          • facebook
                          • Twitter
                          • YouTube
                          • Terms of sale
                          • Website terms of use
                          • Cookie policy
                          • Privacy policy
                          • Legal
                          • Modern slavery statement
                          © 1998-2025 Abcam Limited. All rights reserved.