Host protein mimicry of SARS-CoV-2 receptor binding motif

Viruses frequently produce host protein mimics to stall or exploit cellular machinery within the replication cycle, and many such protein motifs have evolved to the capacity to enhance immune evasion. Coronavirus mimicry has been refined over many successive infections, with SARS-CoV-1, MERS-CoV, and SARS-CoV-2 encoding for many proteins that are homologous to those found in host cells.

In a paper recently uploaded to the bioRxiv* preprint server, structural bioinformatics approaches are employed to investigate the potential mimicry of the receptor-binding motif (RBM) of these three coronaviruses, finding that several proteins from both human and non-human sources were similar to each, with implications regarding the mechanism of infection and tropism of SARS-CoV-2.

Identifying protein mimics

Besides the well-known ACE2 receptor, the major route by which SARS-CoV-2 gains entry into the cell by interaction with the receptor-binding domain (RBD), several other receptors have been reported to facilitate cell entry. Additionally, the spike protein of SARS-CoV-2 has been reported to interact with host protein factors extensively, mimicking particular endogenous proteins and their active sites to lessen host response and assist in replication.

In investigating these interactions, the group firstly constructed the RBM of SARS-CoV-2, SARS-CoV-2, and MERS-CoV computationally, noting that the former two are comprised mainly of hydrophobic and polar non-charged amino acids, being 64.6% identical and conformationally similar. MERS-CoV, however, bears fewer polar non-charged residues and is more distantly related, being only around 20% similar.

A library of proteins was screened against these structures for similarity, with MERS-CoV reporting the greatest number of proteins. Irrelevant proteins, such as those that were only similar to the RBDs when in the closed conformation and thus unable to interact with cell components as a protein mimic, were discarded. The resulting group of proteins largely consisted of cytokines, chemokines, and structures containing epidermal growth factor (EGF) like domains.

EGF-like domains are found largely in the extracellular component of membrane-bound proteins, or are otherwise secreted outside of the cell. They are heavily involved in a variety of immune modulation-related functions, including the facilitation of leukocyte rolling via cell adhesion management. Laminins are a group of extracellular proteins bearing an EFG-like domain that is only revealed during inflammation, attracting immune cells, and EGF-like domains also play a role in the recognition of apoptotic cells.

Each of the three RBMs were seen to potentially mimic a variety of proteins that bear the EGF-like domain, including thrombomodulin, a receptor involved in lessening blood coagulation, the concentration of which has recently been correlated with SARS-CoV-2 severity.

The SARS-CoV-1 and 2 RBMs were both seen to mimic a number of cytokines and chemokines, including interleukin-8, interleukin-18, and fibroblast growth factor 1, among others. Each of these has also been observed to increase in expression during SARS-CoV-2 infection. The SARS-CoV-2, in particular, was also noted to mimic bone morphogenetic protein 2 binding to activin receptor type-2B, and more importantly, bore a resemblance to interleukin-6 and the tumor necrosis factor superfamily, which are very strongly implicated in the response to viral infection.

Toxins sourced from snake, spider, and cone snails were found to be similar to the RBMs, and these toxins are known to bind with receptors involved in the detection of painful stimuli, which the authors suggest could play a role in the observed changing perception of pain and taste during SARS-CoV-2 infection.

Cell adhesion and coagulation pathways are also known to be affected by these toxins. These proteins may have convergently evolved in both animal toxins and viruses to fill the same role. Similarly, one bacterial protein was found to be structurally similar to the MERS-CoV RBM, the adhesion-binding fucosylated histo-blood group antigen of Helicobacter pylori.

The group hopes that this work will support further research into inhibitory drug development, promote antibody design efforts, and reveal the cell entry and immune modulation mechanisms of coronaviruses.

*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:
Michael Greenwood

Written by

Michael Greenwood

Michael graduated from Manchester Metropolitan University with a B.Sc. in Chemistry in 2014, where he majored in organic, inorganic, physical and analytical chemistry. He is currently completing a Ph.D. on the design and production of gold nanoparticles able to act as multimodal anticancer agents, being both drug delivery platforms and radiation dose enhancers.


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

  • APA

    Greenwood, Michael. (2021, April 29). Host protein mimicry of SARS-CoV-2 receptor binding motif. News-Medical. Retrieved on May 14, 2021 from

  • MLA

    Greenwood, Michael. "Host protein mimicry of SARS-CoV-2 receptor binding motif". News-Medical. 14 May 2021. <>.

  • Chicago

    Greenwood, Michael. "Host protein mimicry of SARS-CoV-2 receptor binding motif". News-Medical. (accessed May 14, 2021).

  • Harvard

    Greenwood, Michael. 2021. Host protein mimicry of SARS-CoV-2 receptor binding motif. News-Medical, viewed 14 May 2021,


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... ×
Monoclonal antibody neutralizes all SARS-CoV-2 variants of concern