Engineered Protein Inhibitors of SARS-CoV-2 Entry: Difference between revisions

The enzyme [https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme angiotensin converting enzyme 2] <scene name='10/1077473/Ace2_monomer/1'>(ACE2)</scene> is attached to our cell membranes and then can be bound to a receptor binding domain <scene name='10/1077473/Ace2andrbd2/1'>(RBD)</scene> <ref name="Borkotoky">PMID:36562937</ref>. The virus, SARS-CoV-2, enters our bodies containing a <scene name='10/1077473/Rbd_only/2'>spike protein</scene> protruding from the viral membrane. The RBD on the end of the spike protein <scene name='10/1078124/Ace2andspikecomplex/1'>binds to ACE2</scene>, giving SARS-CoV-2 the ability to enter our host cells <ref name="Jackson">PMID:34611326</ref>. Once the spike protein has access to our host cells, it is able to further infect our cells and spread the virus throughout our bodies. Figure 1 demonstrates the path SARS-CoV-2 takes to get into our cells. In order to create an effective vaccine, the pathway between the spike protein and the RBD needed to be interrupted <ref name=”Zhu”>PMID:36682464</ref>.

===Stability===

One of the most important findings with these De Novo proteins is their high stability, allowing for less delicate forms of administration. Additionally, it was found that the Rosetta built minibinder had a lower thermal stability than the completely De Novo proteins. Looking at the <scene name='10/1078124/Ahb2_internal_stability/1'>nonpolar core of AHB2</scene>, there are only 4 key internal residues significantly contributing to stability, and they are not oriented directly towards the center of the protein for optimal interaction. Comparatively, the <scene name='10/1078124/Lcb1_internal_stability/1'>nonpolar core of LCB1</scene> and <scene name='10/1078124/Lcb3_internal_stability/1'>LCB3</scene> had 5 key internal residues more centrally directed contributing to stability<ref name="Cao">DOI:10.1126/science.abd9909</ref>.