Abstract
The COVID-19 pandemic continues to spread around the world, with several new variants emerging, particularly those of concern (VOCs). Omicron (B.1.1.529), a recent VOC with many mutations in the spike protein’s receptor-binding domain (RBD), has attracted a great deal of scientific and public interest. We previously developed two D-peptide inhibitors for the infection of the original SARS-CoV-2 and its VOCs, alpha and beta, in vitro . Here, we demonstrated that Covid3 and Covid_extended_1 maintained their high-affinity binding (29.4-31.3 nM) to the omicron RBD. Both D-peptides blocked the omicron variant in vitro infection with IC50s of 3.13 and 5.56 μM, respectively. We predicted that Covid3 shares a larger overlapping binding region with the ACE2 binding motif than different classes of neutralizing monoclonal antibodies. We envisioned the design of D-peptide inhibitors targeting the receptor-binding motif as the most promising approach for inhibiting current and future VOCs of SARS-CoV-2, given that the ACE2 binding interface is more limited to tolerate mutations than most of the RBD’s surface.
【초록키워드】 SARS-CoV-2, Mutation, VoC, COVID-19 pandemic, variant, Infection, in vitro, omicron, IC50, Spike protein, Spread, RBD, VOCs, In vitro infection, Alpha, Omicron variant, Beta, B.1.1.529, public interest, inhibitor, receptor-binding motif, neutralizing monoclonal antibodies, binding, ACE2 binding, overlapping, domain, motif, high-affinity binding, approach, IC50s, predicted, blocked, the spike protein, demonstrated, the RBD, inhibiting, 【제목키워드】 SARS-CoV-2, ACE2, concern, lesson, targeting, Future,