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Sci. Adv., 26 Oct 2022 Vol 8, Issue 43 | DOI: 10.1126/sciadv.abq6207 De novo selected hACE2 mimics that integrate hotspot peptides with aptameric scaffolds for binding tolerance of SARS-CoV-2 variants

Minjong Lee ¹, Byunghwa Kang¹, Juhwa Lee ², Jisun Lee ^{3 4}, Sang Taek Jung ^{3 4}, Chang Yun Son ^{2 5}, Seung Soo Oh ^{1 5*}

¹Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea.
²Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea.
³Department of Biomedical Sciences, Graduate School, Korea University, Seoul 02841, South Korea.
⁴BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, South Korea.
⁵Institute for Convergence Research and Education in Advanced Technology (I-CREATE), Yonsei University, Incheon 21983, South Korea.

*Corresponding author : Seung Soo Oh

Abstract

The frequent occurrence of viral variants is a critical problem in developing antiviral prophylaxis and therapy; along with stronger recognition of host cell receptors, the variants evade the immune system-based vaccines and neutralizing agents more easily. In this work, we focus on enhanced receptor binding of viral variants and demonstrate generation of receptor-mimicking synthetic reagents, capable of strongly interacting with viruses and their variants. The hotspot interaction of viruses with receptor-derived short peptides is maximized by aptamer-like scaffolds, the compact and stable architectures of which can be in vitro selected from a myriad of the hotspot peptide-coupled random nucleic acids. We successfully created the human angiotensin-converting enzyme 2 (hACE2) receptor-mimicking hybrid ligand that recruits the hACE2-derived receptor binding domain-interacting peptide to directly interact with a binding hotspot of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Experiencing affinity boosting by ~500% to Omicron, the de novo selected hACE2 mimic exhibited a great binding tolerance to all SARS-CoV-2 variants of concern.

논문정보

형식Research article
게재일2022년 10월 (BRIC 등록일 2023-01-05)
연구진국내 연구진
분야 생명과학 > 분자생물학

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