PMID- 36288301 OWN - NLM STAT- MEDLINE DCOM- 20221028 LR - 20221108 IS - 2375-2548 (Electronic) IS - 2375-2548 (Linking) VI - 8 IP - 43 DP - 2022 Oct 28 TI - De novo selected hACE2 mimics that integrate hotspot peptides with aptameric scaffolds for binding tolerance of SARS-CoV-2 variants. PG - eabq6207 LID - 10.1126/sciadv.abq6207 [doi] LID - eabq6207 AB - 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. FAU - Lee, Minjong AU - Lee M AUID- ORCID: 0000-0002-1729-9876 AD - Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea. FAU - Kang, Byunghwa AU - Kang B AD - Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea. FAU - Lee, Juhwa AU - Lee J AUID- ORCID: 0000-0002-0982-743X AD - Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea. FAU - Lee, Jisun AU - Lee J AD - Department of Biomedical Sciences, Graduate School, Korea University, Seoul 02841, South Korea. AD - BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, South Korea. FAU - Jung, Sang Taek AU - Jung ST AUID- ORCID: 0000-0001-7217-979X AD - Department of Biomedical Sciences, Graduate School, Korea University, Seoul 02841, South Korea. AD - BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, South Korea. FAU - Son, Chang Yun AU - Son CY AUID- ORCID: 0000-0002-0784-6565 AD - Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea. AD - Institute for Convergence Research and Education in Advanced Technology (I-CREATE), Yonsei University, Incheon 21983, South Korea. FAU - Oh, Seung Soo AU - Oh SS AUID- ORCID: 0000-0001-8045-080X AD - Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea. AD - Institute for Convergence Research and Education in Advanced Technology (I-CREATE), Yonsei University, Incheon 21983, South Korea. LA - eng PT - Journal Article DEP - 20221026 PL - United States TA - Sci Adv JT - Science advances JID - 101653440 RN - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2) RN - 0 (Spike Glycoprotein, Coronavirus) RN - 0 (Ligands) RN - 0 (Receptors, Virus) RN - EC 3.4.15.1 (Peptidyl-Dipeptidase A) RN - 0 (Peptides) RN - 0 (Antiviral Agents) RN - 0 (Nucleic Acids) RN - SARS-CoV-2 variants SB - IM MH - Humans MH - Angiotensin-Converting Enzyme 2/genetics MH - SARS-CoV-2/genetics MH - Spike Glycoprotein, Coronavirus/genetics/metabolism MH - Ligands MH - Receptors, Virus/metabolism MH - Peptidyl-Dipeptidase A/metabolism MH - *COVID-19 MH - Protein Binding MH - Peptides/metabolism MH - Antiviral Agents MH - *Nucleic Acids PMC - PMC9604513 EDAT- 2022/10/27 06:00 MHDA- 2022/10/29 06:00 PMCR- 2022/10/26 CRDT- 2022/10/26 14:04 PHST- 2022/10/26 14:04 [entrez] PHST- 2022/10/27 06:00 [pubmed] PHST- 2022/10/29 06:00 [medline] PHST- 2022/10/26 00:00 [pmc-release] AID - abq6207 [pii] AID - 10.1126/sciadv.abq6207 [doi] PST - ppublish SO - Sci Adv. 2022 Oct 28;8(43):eabq6207. doi: 10.1126/sciadv.abq6207. Epub 2022 Oct 26.