Antibodies against SARS may also help combat COVID-19

Scientists have found that a specific antibody against the virus which causes Severe Acute Respiratory Syndrome (SARS) can also neutralise COVID-19

The COVID-19 pandemic has now caused over 3.7 million infections and 260,000 deaths worldwide. Epidemiologists have argued that the most effective way to halt the spread of the pandemic is through vaccines to prevent infections and clever therapeutic discoveries to dull the symptoms of the disease.

The virus responsible for the COVID-19 pandemic, SARS-CoV-2, has a structure on its surface known as a spike glycoprotein, which allows it to enter human cells. Without this glycoprotein the virus would be unable to infect cells, therefore researchers have identified this as the main target of drugs and antibodies.

The most closely-related virus to SARS-CoV-2 is SARS-CoV-1, which was the cause of the 2003 SARS outbreak in Asia. Just like SARS-CoV-2, SARS-CoV-1 uses a spike glycoprotein to interact with ACE2 (angiotensin-converting enzyme 2) receptors on lung cells and infect them. These spike glycoproteins differ only by four amino acids, and both contain two subunits: S1 and S2. Once the spike glycoprotein attaches to the ACE2 receptor, it sheds it S1 subunit, whilst the S2 subunit changes shape to allow the outer surface of the virus, known as the envelope, to fuse with the outer membrane of a cell and release the viral genetic material into the cell.

Biochemists from the University of Washington identified that the spike glycoproteins on SARS-CoV-1 and -CoV-2 bind to ACE2 receptors in a similar way, and hypothesised that antibodies against one, may be effective against the other. Now, researchers from Switzerland have tested this using monoclonal antibodies from memory B cells taken from an individual who was infected by SARS-CoV-1 in 2003, and found that a specific antibody known as S309 was able to neutralise SARS-CoV-2 and other similar coronaviruses by binding to the spike glycoprotein and preventing it from attaching to host ACE2 receptors.

Monoclonal antibodies are those which are produced by identical immune cells, all derived from one parent cell. This means that they all have the same unique structure and are specific to a particular receptor or antigen on a target cell. Memory B cells are responsible for the immune response which occurs after a second infection with the same pathogen. These cells recognise the antigen on the pathogen and quickly produce antibodies to fight the infection.

The antibodies which the scientists extracted from the individual’s blood, despite being initially produced to recognise SARS-CoV-1, were also able to stick to the spike glycoprotein on SARS-CoV-2 and fool the virus into thinking it had attached to an ACE2 receptor. The virus then changed shape in an attempt to enter the cell, but in doing so, became inactivated as it released its genetic material into the surrounding medium.

The scientists were able to protect cells from becoming infected by SARS-CoV-2, thereby providing exciting hope of the development of a vaccine. Despite this, we cannot expect the arrival of a miracle cure, as the unpredictable nature of viruses and infectious diseases means nothing is certain. In the meantime, we should focus on the development of strategies to manage symptoms and increase survival rates of those who become infected.

References:

  1. Walls A.C., Park Y.J., Tortorici M.A. et al. (2020) Structure, Function and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 181(2):281-292. Available from: https://www.cell.com/cell/fulltext/S0092-8674(20)30262-2
  2. Pinto, D., Park, Y., Beltramello, M. et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature (2020). https://doi.org/10.1038/s41586-020-2349-y

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