{"doi":"10.1021/acs.biomac.2c01018","title":"Dendrimer-Peptide Conjugates for Effective Blockade of the Interactions between SARS-CoV-2 Spike Protein and Human ACE2 Receptor","abstract":"The coronavirus disease 2019 (COVID-19) pandemic has threatened the stability of global healthcare, which is becoming an endemic issue. Despite the development of various treatment strategies to fight COVID-19, the currently available treatment options have shown varied efficacy. Herein, we have developed an avidity-based SARS-CoV-2 antagonist using dendrimer-peptide conjugates (DPCs) for effective COVID-19 treatment. Two different peptide fragments obtained from angiotensin-converting enzyme 2 (ACE2) were integrated into a single sequence, followed by the conjugation to poly(amidoamine) (PAMAM) dendrimers. We hypothesized that the strong multivalent binding avidity endowed by dendrimers would help peptides effectively block the interaction between SARS-CoV-2 and ACE2, and this antagonist effect would be dependent upon the generation (size) of the dendrimers. To assess this, binding kinetics of the DPCs prepared from generation 4 (G4) and G7 PAMAM dendrimers to spike protein of SARS-CoV-2 were quantitatively measured using surface plasmon resonance. The larger dendrimer-based DPCs exhibited significantly enhanced binding strength by 3 orders of magnitude compared to the free peptides, whereas the smaller one showed a 12.8-fold increase only. An in vitro assay using SARS-CoV-2-mimicking microbeads also showed the improved SARS-CoV-2 blockade efficiency of the G7-peptide conjugates compared to G4. In addition, the interaction between the DPCs and SARS-CoV-2 was analyzed using molecular dynamics (MD) simulation, providing an insight into how the dendrimer-mediated multivalent binding effect can enhance the SARS-CoV-2 blockade. Our findings demonstrate that the DPCs having strong binding to SARS-CoV-2 effectively block the interaction between ACE2 and SARS-CoV-2, providing a potential as a high-affinity drug delivery system to direct anti-COVID payloads to the virus.","journal":"Biomacromolecules","year":2022,"id":257085,"datarank":0.5574324921082873,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.10807265107518864,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.10807265107518864,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":11,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":875086,"name":"Jiyoon Bu","orcid":"0000-0002-0153-5109","position":1,"is_corresponding":false},{"id":907533,"name":"Philip Mickel","orcid":null,"position":2,"is_corresponding":false},{"id":762239,"name":"Yanxiao Han","orcid":"0000-0002-1684-6073","position":3,"is_corresponding":false},{"id":875090,"name":"Piper A. Rawding","orcid":"0000-0002-9233-9700","position":4,"is_corresponding":false},{"id":646450,"name":"Jianxin Wang","orcid":"0000-0001-8621-543X","position":5,"is_corresponding":false},{"id":906987,"name":"Hanbit Kang","orcid":"0000-0002-1752-7154","position":6,"is_corresponding":false},{"id":907534,"name":"Heejoo Hong","orcid":null,"position":7,"is_corresponding":false},{"id":762240,"name":"Petr Král","orcid":"0000-0003-2992-9027","position":8,"is_corresponding":false},{"id":12354,"name":"Seungpyo Hong","orcid":"0000-0001-9870-031X","position":9,"is_corresponding":false},{"id":875087,"name":"Woo‐Jin Jeong","orcid":"0000-0001-8577-6964","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:25:30.183987Z","pmid":"36562668","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}