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

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[[Image:KdValues.jpg|400 px|right|thumb|Figure 5: The binding affinity values (Kd) and the half maximum inhibitory concentration values (IC50) are shown for ACE2, AHB2, LCB1 and LCB3<ref name="Cao">DOI:10.1126/science.abd9909</ref>.]]
[[Image:KdValues.jpg|400 px|right|thumb|Figure 5: The binding affinity values (Kd) and the half maximum inhibitory concentration values (IC50) are shown for ACE2, AHB2, LCB1 and LCB3<ref name="Cao">DOI:10.1126/science.abd9909</ref>.]]


The inhibitors LCB1 and LCB3 were shown to be the most effective at inhibiting the virus by having the highest affinity for the RBD and as well as the highest neutralization effect as seen in figure 5 <ref name="Cao">DOI:10.1126/science.abd9909</ref>. While AHB2 wasn't as effective as LCB1 and LCB3 at neutralizing the virus, it still showed results of being an effective vaccine as it still had a higher binding affinity to the RBD compared to ACE2. All three inhibitors show more advantages as a vaccine compared to antibodies due to their small size, stability and their ability to be quickly modified <ref name="Cao">DOI:10.1126/science.abd9909</ref>. The use of mini-inhibitors through the de novo protein design has also shown results in being able to control cell function and detecting protein activity within the cell <ref name= "Weinberg">PMID:38293112</ref>.
All in all, minibinders designed to inhibit binding of ACE2 to the spike protein have revealed promising potential. The inhibitors LCB1 and LCB3 were shown to be the most effective at inhibiting the virus by having the highest affinity for the RBD, and as well as the highest neutralization effect as seen in figure 5 <ref name="Cao">DOI:10.1126/science.abd9909</ref>. While AHB2 wasn't as effective as LCB1 and LCB3 at neutralizing the virus, it still showed results of being an effective vaccine, as it still had a higher binding affinity to the RBD compared to ACE2. All three inhibitors show more advantages as a vaccine compared to antibodies due to their small size, stability, and their ability to be quickly modified <ref name="Cao">DOI:10.1126/science.abd9909</ref>. The use of mini-inhibitors through the de novo protein design has also shown results in being able to control cell function and detecting protein activity within the cell <ref name= "Weinberg">PMID:38293112</ref>.


The limitation behind the design of AHB2, it was specifically made from ACE2 making it an inhibitor that can't be universally used to fight other viruses. The biggest limitation regarding the de novo designed inhibitors, is there is a large protein bank that is used as reference when creating the inhibitors. With an abundance of inhibitors created with varying mutations, difficulty arises when determining which mutations will be most effective for the specific virus being neutralized in a steadfast manner <ref name="Cao">DOI:10.1126/science.abd9909</ref>.  
The limitation behind the design of AHB2 was that it was specifically made from ACE2, making it an inhibitor that can't be universally used to fight other viruses. The biggest limitation regarding the de novo designed inhibitors is that there is a large protein bank that is used as reference when creating the inhibitors. With an abundance of inhibitors created with varying mutations, difficulty arises when determining which mutations will be most effective for the specific virus being neutralized in a steadfast manner <ref name="Cao">DOI:10.1126/science.abd9909</ref>.  


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