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As we wait for vaccines, let’s not forget drugs. We still need effective drugs against SARS-CoV-2 (and other coronaviruses that will infect humans in the future).
There is an approach that might prevent SARS-CoV-2 from infecting cells that is ingenious and worth unpacking.
There is an approach that might prevent SARS-CoV-2 from infecting cells that is ingenious and worth unpacking.
By now, you all know about that the SARS-CoV-2 spike has to bind to the ACE2 receptor on some cells for infection to proceed. You also know that antibodies generated from infection or vaccines block the spike by attaching to it better.
You also know (all too well) that some mutations to the spike can potentially cause greater transmission and give rise to strains that can evade host immune responses. This is one of the reasons experts are worried about the new strains that are coming up around the world.
One approach is “passive immunization” in which we provide the body with antibodies that attach to a part of the spike so that it can no longer bind to the ACE2 receptor. Some monoclonal antibodies that do this have been approved for use.
But another really cool approach to stopping infection is to inject free (soluble) ACE2 receptors. The idea here is the virus spike recognizes the decoy receptors better than the ones that are gateways to cells. We trick the virus into thinking it's initiating infection.
I've discussed this strategy as well as every other mainstream strategy for COVID-19 drugs and vaccines in the book ( https://www.amazon.in/COVID-19-Separating-Dr-Anirban-Mahapatra/dp/0670094374) but in the rest of the thread I want to talk about where we are at with this and why this might work.
APEIRON Biologics has a recombinant form of the human ACE2 receptor in phase II clinical trials right now. The results should be out in the next few months. Their preclinical ( https://www.cell.com/pb-assets/products/coronavirus/CELL_CELL-D-20-00739.pdf) and phase I studies have already been published. ( https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30418-5/fulltext)
But on Monday, a new study was published. In this study an engineered version of the ACE2 receptor recognizes the viral spike even better than earlier versions. This seems to work very potently in cell culture.
The science is moving remarkably fast. https://www.nature.com/articles/s41594-020-00549-3
The science is moving remarkably fast. https://www.nature.com/articles/s41594-020-00549-3
The most important take-home message is that just as viruses can mutate to become more transmissible and to evade immune responses, we can also rationally tweak vaccines and drugs (using a structure-based approach) to hit back at modified variants.
