Spike is essential for the infection
The spike protein is essential for the virus: It uses it to dock onto the cells it attacks. In the process, the protein binds to a molecule on the surface of its victims called ACE2, which effectively locks into the spike protein, much like a ski boot in a ski binding. The virus then fuses with the cell and reprograms it to produce numerous new viruses. "The vast majority of antibodies we know today prevent docking," Mayer explains. "They attach to the part of the spike protein responsible for recognizing ACE2, which is the receptor binding domain, or RBD."
The now isolated aptamer with the abbreviation SP6 also binds to the spike protein, but at a different site. "SP6 does not prevent viruses from docking to target cells," explains Prof. Dr. Michael Famulok of the LIMES Institute, who also works at the caesar research center in Bonn. "Nevertheless, it reduces the level of cell infection by the virus; we do not yet know which mechanism is responsible for this." The researchers did not use real coronaviruses in their experiments, but so-called pseudoviruses. These carry the spike protein on their surface; however, they cannot cause disease. "We now need to see if our results are confirmed in real viruses," Famulok therefore emphasizes.
New Achilles heel of coronavirus?
If so, in the medium term the work could for instance result in a kind of nasal spray that protects against coronavirus infection for a few hours. The necessary studies will certainly take months to complete. Irrespective of this, however, the results may help to better understand the mechanisms involved in infection. This is all the more important because the existing active ingredients mainly target the receptor domain. In the so-called "British mutation", this domain is altered so that it binds more strongly to ACE2. "The more such mutations accumulate, the greater the risk that the available drugs and vaccines will no longer work," stresses Günter Mayer.
"Our study may draw attention to an alternative Achilles’ heel of the virus."
The results are also evidence of successful cooperation: Mayer and his postdoctoral researcher Dr. Anna Maria Weber were primarily responsible for characterizing the aptamer. Prof. Famulok’s group at the caesar research center was responsible for conducting the pseudovirus experiments, which were led by his colleague Dr. Anton Schmitz. Famulok and Mayer are members of the Transdisciplinary Research Areas "Life & Health" and "Building Blocks of Matter and Fundamental Interactions". Mayer also heads the Center of Aptamer Research and Development (CARD) at the University of Bonn.