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Dynamic View of Spike Protein Reveals Prime Targets for COVID-19 Treatments

Posted on by Dr. Francis Collins

SARS-CoV-2’s spike protein showing attached glycans and regions for antibody binding.
Credit: Sikora M, PLoS Comput Biol, 2021

This striking portrait features the spike protein that crowns SARS-CoV-2, the coronavirus that causes COVID-19. This highly flexible protein has settled here into one of its many possible conformations during the process of docking onto a human cell before infecting it.

This portrait, however, isn’t painted on canvas. It was created on a computer screen from sophisticated 3D simulations of the spike protein in action. The aim was to map its many shape-shifting maneuvers accurately at the atomic level in hopes of detecting exploitable structural vulnerabilities to thwart the virus.

For example, notice the many chain-like structures (green) that adorn the protein’s surface (white). They are sugar molecules called glycans that are thought to shield the spike protein by sweeping away antibodies. Also notice areas (purple) that the simulation identified as the most-attractive targets for antibodies, based on their apparent lack of protection by those glycans.

This work, published recently in the journal PLoS Computational Biology [1], was performed by a German research team that included Mateusz Sikora, Max Planck Institute of Biophysics, Frankfurt. The researchers used a computer application called molecular dynamics (MD) simulation to power up and model the conformational changes in the spike protein on a time scale of a few microseconds. (A microsecond is 0.000001 second.)

The new simulations suggest that glycans act as a dynamic shield on the spike protein. They liken them to windshield wipers on a car. Rather than being fixed in space, those glycans sweep back and forth to protect more of the protein surface than initially meets the eye.

But just as wipers miss spots on a windshield that lie beyond their tips, glycans also miss spots of the protein just beyond their reach. It’s those spots that the researchers suggest might be prime targets on the spike protein that are especially promising for the design of future vaccines and therapeutic antibodies.

This same approach can now be applied to identifying weak spots in the coronavirus’s armor. It also may help researchers understand more fully the implications of newly emerging SARS-CoV-2 variants. The hope is that by capturing this devastating virus and its most critical proteins in action, we can continue to develop and improve upon vaccines and therapeutics.


[1] Computational epitope map of SARS-CoV-2 spike protein. Sikora M, von Bülow S, Blanc FEC, Gecht M, Covino R, Hummer G. PLoS Comput Biol. 2021 Apr 1;17(4):e1008790.


COVID-19 Research (NIH)

Mateusz Sikora (Max Planck Institute of Biophysics, Frankfurt, Germany)

The surprising properties of the coronavirus envelope (Interview with Mateusz Sikora), Scilog, November 16, 2020.


  • DR. SAUMYA PANDEY, PH.D. says:

    Amazing spike protein 3D-mapping Covid-19 virus-envelope dissection with fascinating avenues for future dynamic collaborations-based immunogenic-immunomodulatory clinical research focusing on biomarkers/pharmacological scaffolds in Covid-19 susceptibility in American and Asian-Indian cohorts of varying ethnicities!

  • N.H. says:

    Really interesting.

  • Sue Gilbertson says:

    Does this imply that if we remove sugar from our diet that we will be safer?

  • Michael Sheikh says:

    While this picture shows a spike protein covered in sugars what it doesn’t show is the galectin fold if its rotated on its y axis another 90 degrees. This is the Achilles heel of the spike protein and a carbohydrate drug can attach to it. In fact, a carbohydrate drug can prevent viral entry of SAR CoV-2. It was demonstrated in human clinical trials and resulted in the elimination of the virus from the blood, the patients felt better, and they got immunized with high levels of IgG to protect them against reinfection.

    We must show everyone the weak side of the spike protein but the picture needs to be rotated.

  • Andargachew Mulu says:

    This is an interesting figure and a nice work. But, what would be the picture in real life time in different ecosystem and conconrent infection and varied nutritional menu?

  • zuccheri gianni says:

    Only a twin gets sick with Covid19: chiral forms of the virus?
    With great interest I read what your article reports “Dynamic View of Spike Protein Reveals Prime Targets for COVID-19 Treatments “and recalling the chirality of carbohydrates, I cite the case of two twins aged about one year: one falls ill with Covid19 (in hospital observation for a few days) while the other remains completely asymptomatic. They had no external contacts, both looked after only by their mother
    (asymptomatic but with positive Swab), familial infection from the father (moderate respiratory symptoms).
    It has happened that we have observed family groups in which the clinical evolution of the Covid19 disease was very different. Evaluating only people deemed to have no previous pathologies, sometimes one member becomes very ill while another is completely asymptomatic, even if in close contact. Excluding vaccination or swab positive in previous periods, neither age nor sex or blood groups were determinative.
    So I work out a hypothesis.
    In viral structures, especially on the Spike protein, glycans, long-chain carbohydrates composed of monomers, are abundantly present. These can have a right-handed or left-handed form (Chirality: molecule that cannot be superimposed on its own mirror image in three dimensions).
    The glycans present on the cell surface play a fundamental role in the interaction of cells with the environment: they are carbohydrate-based molecules but can also covalently bind lipids, proteins, nucleic acids to others. They can bind individual monosaccharide residues in different ways, even non-linearly, through the glycosidic bond. Each monosaccharide has different hydroxyl groups that can be a “binding” site by another monomer through its anomeric position.
    In the infected person, viral replication could have a monomer assembly in the D form or L form, producing copies of differently aggressive and contagious viruses (calling A aggressive and S soft).
    The host response mechanisms to the virus are varied, but if the patient simultaneously produces two different virion lines (due to the D or L form of the same monomer), the one who is close if he takes A or S will have a different viral form from face.
    I remember that Chirality concerns the assembly of carbohydrate monomers also in the vegetable kingdom.
    Thanks for your attention.

  • Zuccheri Gianni says:

    A colleague points out to me that in twins I have to consider that the immune response depends on epigenetic factors: diet, sedentary lifestyle, environment, .. But at one year of age what the differences might escape me, maybe we can think only of the sleep factor.
    On the contrary, for older individuals, the causes of different immune responses are analyzed in various studies. And I therefore come to ask: would a chiral assembly of the ACE2 receptor components be plausible, with a consequent different individual response deriving from the bond with the Spike?
    Thanks for your attention.

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