De novo design of protein peptides to block association of the SARS-CoV-2 spike protein with human ACE2

• DOI: 10.18632/aging.103416
• Publication Date: 2020-06-16T21:37:15Z
• Authors: Xiaoqiang Huang; Robin Pearce; Yang Zhang
• Keywords: spike protein; 2019-20 coronavirus outbreak; Sars virus; Coronavirus; Association (psychology)

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