The COVID-19 global pandemic has raged due to the rampant spread of the SARS-CoV-2 virus, and resultant mutant strains. SARS-CoV-2 binds to ACE2 receptors in the lung cells to infect a new host, and the virus may remain dormant while the host remains asymptomatic and infective. Our project seeks to develop a cost-effective antiviral therapy that may bridge the gap between spreading infections and the current vaccine rollout effort. The virus’s 3D structure shows a conserved receptor-binding domain (RBD) from SARS; during infection, the RBD binds to the ACE-2 receptor in the lungs. An identified peptide, RBD-peptide 1 – RP1, may prevent infection by coating the viral spike protein and preventing binding. We propose that by attaching a self-assembling domain (SAP) to RP1, we may increase the stability of that linkage and coat viral particles such that the immune system is alerted and clears the foreign bodies prior to infection. SAPs were synthesized, formulated in DI water at pH 7 with equimolar 10x PBS or Ca2+ added as a counterion for K or E terminated peptides, respectively. AFM and SEM were used to characterize the nanofibrous structure. AFM shows the formation of 10-15nm wide 1-2nm thick ribbon-like fibers of µm-mm length that entangle and solvate to create hydrogels at 0.1-4w% in phosphate buffer. SEM imaging of critical point dried hydrogels shows the fibrous sponge structure of our SAP. RP1 or SAP-RP1 can bind viral particles, preventing the binding to the ACE-2 receptor. Fibrillation of peptides on the viral surface may target the virion for endocytosis and proteolytic cleavage. We demonstrated the nanofibrillar structure of our SAP, the ability to functionalize its formulation through the addition of RP1, and the binding affinity of RP1 alone to ACE-2. Ongoing and future work seeks to determine in vitro efficacy and in vivo safety, binding kinetics, opsonization properties, and cytopathogenic effect of the SARS-CoV-2 virus regarding SAP-RP1.

Opsonization of SARS-CoV-2 through self-assembling peptides

ACS Fall 2021

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