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

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[[Image:AHB2_Method.png|400 px|right|thumb|Figure 2: The use of the Rosetta Blueprint protein design to create the AHB2 inhibitor (7JZL & 7UHB).]]
[[Image:AHB2_Method.png|400 px|right|thumb|Figure 2: The use of the Rosetta Blueprint protein design to create the AHB2 inhibitor (7JZL & 7UHB).]]


The first mini-binder to be created to combat COVID-19 is called <scene name='10/1078124/Ahb2_general/1'>AHB2</scene>. In order to ensure that the mini-binder would bind to the same RBD that the ACE2 was bound to, AHB2 was designed by looking at the specific sequence of ACE2 to find the alpha-helix that makes interactions with the spike receptor binding domain. This design process is referred to as the Rosetta Blueprint protein design. Figure 2 shows the RBD trimer with one part of ACE2 being used for the reference alpha helix to create AHB2 <ref name="Cao">PMID:32907861</ref>.
The first mini-binder to be created to combat COVID-19 is called <scene name='10/1078124/Ahb2_general/2'>AHB2</scene>. In order to ensure that the mini-binder would bind to the same RBD that the ACE2 was bound to, AHB2 was designed by looking at the specific sequence of ACE2 to find the alpha-helix that makes interactions with the spike receptor binding domain. This design process is referred to as the Rosetta Blueprint protein design. Figure 2 shows the RBD trimer with one part of ACE2 being used for the reference alpha helix to create AHB2 <ref name="Cao">PMID:32907861</ref>.


[[Image:LCB_Method.png|400 px|right|thumb|Figure 3:The use of the De Novo protein design to create the LCB1 and LCB3 inhibitors (7JZL).]]
[[Image:LCB_Method.png|400 px|right|thumb|Figure 3:The use of the De Novo protein design to create the LCB1 and LCB3 inhibitors (7JZL).]]


As the AHB2 inhibitors were tested and found to be effective, it was then time to manipulate the mini-binders to create a more effective vaccine. A rotamer interaction field docking method with in silico mini-proteins was used with a scaffold library to generate binders to more distinct regions of the RBD surface <ref name="Cao"/>. This method is known as the de novo protein design and it is how the <scene name='10/1078124/Lcb1_general/1'>LCB1</scene> and LCB3 mini-binders were created. Figure 3 shows the different LCBs pulled from the scaffold library to create the different LCB inhibitors.  
As the AHB2 inhibitors were tested and found to be effective, it was then time to manipulate the mini-binders to create a more effective vaccine. A rotamer interaction field docking method with in silico mini-proteins was used with a scaffold library to generate binders to more distinct regions of the RBD surface <ref name="Cao"/>. This method is known as the de novo protein design and it is how the <scene name='10/1078124/Lcb1_general/2'>LCB1</scene> and <scene name='10/1078124/Lcb3_general/1'>LCB3</scene> mini-binders were created. Figure 3 shows the different LCBs pulled from the scaffold library to create the different LCB inhibitors.  


===Stability===
===Stability===
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