Sandbox Reserved 1849: Difference between revisions
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===What are Minibinders?=== | ===What are Minibinders?=== | ||
These mini proteins target the interaction between ACE2 and COVID-19 spike protein <ref name="Longxing">PMID:32907861</ref>. The minibinders are small proteins carefully designed to bind to the COVID-19 spike protein with a greater affinity than ACE2 <ref name="Longxing">PMID:32907861</ref>. These minibinders were able to reduce the viral burden of SARS-CoV-2 in mice <ref name="Case">PMID:34192518</ref>. These proteins were de novo (from scratch) designs to mimic the ACE2 helix, but have a lower dissociation constant, yielding a greater affinity for the spike protein <ref name="Longxing">PMID:32907861</ref>. The binding region between <scene name='10/1075251/Ace2_and_rbd/2'>spike protein and ACE2</scene> can give a better explanation as to how these proteins were designed. | These mini proteins target the interaction between ACE2 and COVID-19 spike protein <ref name="Longxing">PMID:32907861</ref>. The minibinders are small proteins carefully designed to bind to the COVID-19 spike protein with a greater affinity than ACE2 <ref name="Longxing">PMID:32907861</ref>. These minibinders were able to reduce the viral burden of SARS-CoV-2 in mice <ref name="Case">PMID:34192518</ref>. These proteins were de novo (from scratch) designs to mimic the ACE2 helix, but have a lower dissociation constant, yielding a greater affinity for the spike protein <ref name="Longxing">PMID:32907861</ref>. The binding region between <scene name='10/1075251/Ace2_and_rbd/2'>spike protein and ACE2</scene> can give a better explanation as to how these proteins were designed. | ||
[[Image:Untitled presentation.jpg| | [[Image:Untitled presentation.jpg|700 px|right|thumb|Figure 1. Image of the individual helices of AHB2, LCB1, and LCB3, respectively.]] | ||
===COVID-19 Disease Pathway=== | ===COVID-19 Disease Pathway=== | ||
Understanding the pathway of the COVID-19 virus is essential to understanding the mechanism in which the virus’ surface proteins attach to the mini binders. The COVID-19 virus has spike proteins on its surface that bind to the host cell receptor, known as ACE2, and this allows the virus to remain anchored to the host for viral entry <ref name="Sang">PMID:36499120</ref>. When the spike protein binds to the receptor, ACE2 for example, the cell membrane-associated protease, protease serine 2 TMPRSS2 promotes viral entry by activating the spike protein <ref name="Huang">PMID:32747721</ref>. The activated spike protein is able to cleave itself into S1 and S2 subunits <ref name="Huang">PMID:32747721</ref>. The S2 subunit is in charge of viral entry and does this through conformational changes <ref name="Huang">PMID:32747721</ref>. The S2 subunit will insert it's FP domain into the host cell's membrane, and this will trigger an interaction with the HR2 domain and HR1 trimer to form the 6-helical bundle to bring the viral envelope and cell membrane in close enough distance for viral fusion and ultimately viral entry <ref name="Huang">PMID:32747721</ref>. Once the virus is within the host cell, it is able to translate viral proteins, eliciting an immune response and spreading the viral particles throughout the body <ref name="Huang">PMID:32747721</ref>. | Understanding the pathway of the COVID-19 virus is essential to understanding the mechanism in which the virus’ surface proteins attach to the mini binders. The COVID-19 virus has spike proteins on its surface that bind to the host cell receptor, known as ACE2, and this allows the virus to remain anchored to the host for viral entry <ref name="Sang">PMID:36499120</ref>. When the spike protein binds to the receptor, ACE2 for example, the cell membrane-associated protease, protease serine 2 TMPRSS2 promotes viral entry by activating the spike protein <ref name="Huang">PMID:32747721</ref>. The activated spike protein is able to cleave itself into S1 and S2 subunits <ref name="Huang">PMID:32747721</ref>. The S2 subunit is in charge of viral entry and does this through conformational changes <ref name="Huang">PMID:32747721</ref>. The S2 subunit will insert it's FP domain into the host cell's membrane, and this will trigger an interaction with the HR2 domain and HR1 trimer to form the 6-helical bundle to bring the viral envelope and cell membrane in close enough distance for viral fusion and ultimately viral entry <ref name="Huang">PMID:32747721</ref>. Once the virus is within the host cell, it is able to translate viral proteins, eliciting an immune response and spreading the viral particles throughout the body <ref name="Huang">PMID:32747721</ref>. | ||
