Sandbox Reserved 1847: Difference between revisions
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===COVID-19 Disease Pathway=== | ===COVID-19 Disease Pathway=== | ||
Minibinders mimic the pathway of the SARS-CoV-2 virus attachment to the cell surface receptors. In the standard process, the SARS-CoV-2 surface spike proteins bind to the host cell receptor, ACE2. This anchors to the host for viral entry <ref name="Sang">PMID:36499120</ref. When the spike protein binds to the ACE2 receptor, the cell membrane-associated protease, TMPRSS2, activates the spike protein, promoting viral entry <ref name="Huang">PMID:32747721</ref>. The activated spike protein then cleaves itself into S1 and S2 subunits <ref name="Huang">PMID:32747721</ref>. The S1 subunit contains a receptor binding domain that recognizes and binds to ACE2 <ref name="Huang">PMID:32747721</ref>. The S2 subunit undergoes a conformational change which permits viral entry <ref name="Huang">PMID:32747721</ref>. The S2 domain has a fusion peptide (FP) domain that will help regulate membrane fusion by disrupting and connecting the host cell’s membrane <ref name="Huang">PMID:32747721</ref>. The S2 domain is also composed of HR1 and HR2 subunits, which are heptapeptide sequences involved in the entry of SARS-CoV-2. HR1 is located at the C-terminal domain of a hydrophobic FP, and HR2 is located at the N-terminal of the transmembrane domain <ref name="Huang">PMID:32747721</ref>. In this conformational change, the S2 subunit inserts its FP domain into the host cell's membrane. Once the host cell’s membrane is penetrated, this triggers an interaction with the HR2 domain and HR1 trimer, forming the 6-helical bundle. The bundle brings the viral envelope and cell membrane in close enough distance for viral fusion and ultimately viral entry <ref name="Huang">PMID:32747721</ref>. Once inside, the virus translates viral proteins, eliciting an immune response and spreading the viral particles throughout the body <ref name="Huang">PMID:32747721</ref>. | |||
===COVID-19 Viral Infection Interruption=== | ===COVID-19 Viral Infection Interruption=== | ||
The primary goal of the mini binders is to prevent the spike proteins from binding to ACE2, and when the mini binders are bound to the spike protein, the virus is unable to anchor itself to the host protein <ref name="Longxing">PMID:32907861</ref>. Because the mini binders have a greater binding affinity than ACE2 for the spike protein, they are able to effectively prevent the entry of the virus and ultimately prevent an immune response <ref name="Longxing">PMID:32907861</ref>. Targeting this specific interaction between the COVID-19 spike protein has proven effective and is hopeful target for future therapeutics to treat the virus <ref name="Huang">PMID:32747721</ref>. LCB1 proved to be quite effective at weakening the immune response, compared to the other mini binders, which can be explained by the binding interface between the spike protein and LCB1 <ref name="Longxing">PMID:32907861</ref>. | The primary goal of the mini binders is to prevent the spike proteins from binding to ACE2, and when the mini binders are bound to the spike protein, the virus is unable to anchor itself to the host protein <ref name="Longxing">PMID:32907861</ref>. Because the mini binders have a greater binding affinity than ACE2 for the spike protein, they are able to effectively prevent the entry of the virus and ultimately prevent an immune response <ref name="Longxing">PMID:32907861</ref>. Targeting this specific interaction between the COVID-19 spike protein has proven effective and is hopeful target for future therapeutics to treat the virus <ref name="Huang">PMID:32747721</ref>. LCB1 proved to be quite effective at weakening the immune response, compared to the other mini binders, which can be explained by the binding interface between the spike protein and LCB1 <ref name="Longxing">PMID:32907861</ref>. | ||
