The outbreak of COVID-19 has now become a global pandemic that has severely impacted lives and economic stability. There is, however, no effective antiviral drug that can be used to treat COVID-19 to date. Built on the fact that SARS-CoV-2 initiates its entry into human cells by the receptor binding domain (RBD) of its spike protein binding to the angiotensin-converting enzyme 2 (hACE2), we extended a recently developed approach, EvoDesign, to design multiple peptide sequences that can competitively bind to the SARS-CoV-2 RBD to inhibit the virus from entering human cells. The protocol starts with the construction of a hybrid peptidic scaffold by linking two fragments grafted from the interface of the hACE2 protein (a.a. 22-44 and 351-357) with a linker glycine, which is followed by the redesign and refinement simulations of the peptide sequence to optimize its binding affinity to the interface of the SARS-CoV-2 RBD. The binding experiment analyses showed that the designed peptides exhibited a significantly stronger binding potency to hACE2 than the wild-type hACE2 receptor (with -53.35 vs. -46.46 EvoEF2 energy unit scores for the top designed and wild-type peptides, respectively). This study demonstrates a new avenue to utilize computationally designed peptide motifs to treat the COVID-19 disease by blocking the critical spike-RBD and hACE2 interactions.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, peptide, antiviral therapeutic, 【초록키워드】 protocol, virus, angiotensin-converting enzyme 2, binding affinity, Spike protein, antiviral drug, hACE2, Receptor binding domain, COVID-19 disease, global pandemic, stability, outbreak, RBD, peptides, receptor, experiment, Critical, interactions, binding, Analysis, glycine, sequence, human cells, treat, wild-type, motif, human cell, hACE2 protein, approach, effective, linker, significantly, inhibit, exhibited, can be used, initiate, impacted, the SARS-CoV-2, wild-type hACE2, 【제목키워드】 Spike protein, human ACE2, Protein, association, the SARS-CoV-2,