Sandbox Reserved 1847: Difference between revisions

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These minibinders are small proteins, modeled similarly to the ACE2 and SARS-CoV-2 spike protein. There were two strategies utilized. One strategy included directly incorporating the ACE2 helix of the RBD and creating more interactions, increasing the binding affinity of the minibinders <ref name="Longxing">PMID:32907861</ref>. The other strategy was designing the minibinders completely from scratch, completely dependent on the RBD <ref name="Longxing">PMID:32907861</ref>. AHB2 utilized the first method, incorporating the ACE2 helix, while LCB1 and LCB3 utilized the second method <ref name="Longxing">PMID:32907861</ref> .

==Implications==

===Potency of the minibinders===

Examining the IC50 values of the various mini binders gives quantitative data to the effectiveness of the proteins in preventing an immune response. The highest IC50 was AHB2 (15.5 nM), followed by LCB3 (40.1 pM) LCB1 (23.5 pM) <ref name="Longxing">PMID:32907861</ref>. The higher IC50 indicates a larger concentration of mini binder required to inhibit the biological process. Both LCB1 and LCB3 proved to be significantly more effective than AHB2, LCB1 and LCB3 were within 3-fold of the most potent anti-Spike monoclonal antibodies described to date <ref name="Longxing">PMID:32907861</ref>.

===Results from mice study===

The effectiveness of the most potent minibinder was examined in mice. LCB1 was administered to the mice via nasal delivery. As expected, compared to control mini protein, the LCB1 was significantly more effective at reducing the viral burden, diminishing the immune cell infiltration, and inflammation <ref name="Case">PMID:34192518</ref>. The virus was not detected in the lungs 4-7 days post-infection, and the spleen, heart, and brain had viral RNA at very low concentrations <ref name="Case">PMID:34192518</ref>.

===Benefits of minibinders over other therapeutics===

The size of these mini binders is a large reason why they are so effective. The minibinders have a 20-fold more potential for nebulization compared with antibodies, and the molecular weight of the minibinders is 5% of a full antibody molecule <ref name="Longxing">PMID:32907861</ref>. When the LCB1 wasa attached to a human IgG domain to enhance bioavailability, staying in the body longer, LCB1 was less effective <ref name="Case">PMID:34192518</ref>. This is likely due to the increase in size when bound to the antibody. The high stability of the mini binders allows them to be administered as a gel via nebulization <ref name="Longxing">PMID:32907861</ref>. Future directions of mini binders are to increase the efficiency of the process to obtain a sequence for pathogen neutralizing designs more promptly <ref name="Longxing">PMID:32907861</ref>. Given that there are only a small number of antibody therapies and vaccines approved for treatment of SARS-CoV-2, minibinders as potential therapeutics may lay the foundation for similar minibinders designs as treatments for other viruses.

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@@ Line 24: / Line 24: @@
 These minibinders are small proteins, modeled similarly to the ACE2 and SARS-CoV-2 spike protein. There were two strategies utilized. One strategy included directly incorporating the ACE2 helix of the RBD and creating more interactions, increasing the binding affinity of the minibinders <ref name="Longxing">PMID:32907861</ref>. The other strategy was designing the minibinders completely from scratch, completely dependent on the RBD <ref name="Longxing">PMID:32907861</ref>. AHB2 utilized the first method, incorporating the ACE2 helix, while LCB1 and LCB3 utilized the second method <ref name="Longxing">PMID:32907861</ref> .
+==Implications==
+===Potency of the minibinders===
+Examining the IC50 values of the various mini binders gives quantitative data to the effectiveness of the proteins in preventing an immune response. The highest IC50 was AHB2 (15.5 nM), followed by LCB3 (40.1 pM) LCB1 (23.5 pM) <ref name="Longxing">PMID:32907861</ref>. The higher IC50 indicates a larger concentration of mini binder required to inhibit the biological process. Both LCB1 and LCB3 proved to be significantly more effective than AHB2,  LCB1 and LCB3 were within 3-fold of the most potent anti-Spike monoclonal antibodies described to date <ref name="Longxing">PMID:32907861</ref>.
+===Results from mice study===
+The effectiveness of the most potent minibinder was examined in mice. LCB1 was administered to the mice via nasal delivery. As expected, compared to control mini protein, the LCB1 was significantly more effective at reducing the viral burden, diminishing the immune cell infiltration, and inflammation <ref name="Case">PMID:34192518</ref>. The virus was not detected in the lungs 4-7 days post-infection, and the spleen, heart, and brain had viral RNA at very low concentrations <ref name="Case">PMID:34192518</ref>.
+===Benefits of minibinders over other therapeutics===
+The size of these mini binders is a large reason why they are so effective. The minibinders have a 20-fold more potential for nebulization compared with antibodies, and the molecular weight of the minibinders is 5% of a full antibody molecule <ref name="Longxing">PMID:32907861</ref>. When the LCB1 wasa attached to a human IgG domain to enhance bioavailability, staying in the body longer, LCB1 was less effective <ref name="Case">PMID:34192518</ref>. This is likely due to the increase in size when bound to the antibody. The high stability of the mini binders allows them to be administered as a gel via nebulization <ref name="Longxing">PMID:32907861</ref>. Future directions of mini binders are to increase the efficiency of the process to obtain a sequence for pathogen neutralizing designs more promptly <ref name="Longxing">PMID:32907861</ref>. Given that there are only a small number of antibody therapies and vaccines approved for treatment of SARS-CoV-2, minibinders as potential therapeutics may lay the foundation for similar minibinders designs as treatments for other viruses.