PMID- 35598822 OWN - NLM STAT- MEDLINE DCOM- 20220608 LR - 20230126 IS - 1873-1899 (Electronic) IS - 0734-9750 (Print) IS - 0734-9750 (Linking) VI - 59 DP - 2022 Oct TI - Native, engineered and de novo designed ligands targeting the SARS-CoV-2 spike protein. PG - 107986 LID - S0734-9750(22)00082-9 [pii] LID - 10.1016/j.biotechadv.2022.107986 [doi] AB - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the deadly coronavirus disease 2019 (Covid-19) and is a concerning hazard to public health. This virus infects cells by establishing a contact between its spike protein (S-protein) and host human angiotensin-converting enzyme 2 (hACE2) receptor, subsequently initiating viral fusion. The inhibition of the interaction between the S-protein and hACE2 has immediately drawn attention amongst the scientific community, and the S-protein was considered the prime target to design vaccines and to develop affinity ligands for diagnostics and therapy. Several S-protein binders have been reported at a fast pace, ranging from antibodies isolated from immunised patients to de novo designed ligands, with some binders already yielding promising in vivo results in protecting against SARS-CoV-2. Natural, engineered and designed affinity ligands targeting the S-protein are herein summarised, focusing on molecular recognition aspects, whilst identifying preferred hot spots for ligand binding. This review serves as inspiration for the improvement of already existing ligands or for the design of new affinity ligands towards SARS-CoV-2 proteins. Lessons learnt from the Covid-19 pandemic are also important to consolidate tools and processes in protein engineering to enable the fast discovery, production and delivery of diagnostic, prophylactic, and therapeutic solutions in future pandemics. CI - Copyright (c) 2022 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Costa, Carlos F S AU - Costa CFS AD - Associate Laboratory i4HB - Institute for Health and Bioeconomy, School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Department of Chemistry, School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal. FAU - Barbosa, Armenio J M AU - Barbosa AJM AD - Associate Laboratory i4HB - Institute for Health and Bioeconomy, School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Department of Chemistry, School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal. FAU - Dias, Ana Margarida G C AU - Dias AMGC AD - Associate Laboratory i4HB - Institute for Health and Bioeconomy, School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Department of Chemistry, School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal. FAU - Roque, Ana Cecilia A AU - Roque ACA AD - Associate Laboratory i4HB - Institute for Health and Bioeconomy, School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Department of Chemistry, School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal. Electronic address: cecilia.roque@fct.unl.pt. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20220519 PL - England TA - Biotechnol Adv JT - Biotechnology advances JID - 8403708 RN - 0 (Ligands) RN - 0 (Spike Glycoprotein, Coronavirus) RN - 0 (spike protein, SARS-CoV-2) SB - IM MH - *COVID-19/genetics/metabolism MH - Humans MH - *Ligands MH - Pandemics MH - Protein Binding MH - SARS-CoV-2/genetics MH - *Spike Glycoprotein, Coronavirus/chemistry/genetics/metabolism PMC - PMC9119173 OTO - NOTNLM OT - ACE2 OT - Affinity ligands OT - SARS-CoV-2 OT - Spike OT - de novo design COIS- The authors declare no financial or commercial conflict of interest. EDAT- 2022/05/23 06:00 MHDA- 2022/06/09 06:00 PMCR- 2022/05/19 CRDT- 2022/05/22 19:33 PHST- 2021/09/14 00:00 [received] PHST- 2022/04/29 00:00 [revised] PHST- 2022/05/16 00:00 [accepted] PHST- 2022/05/23 06:00 [pubmed] PHST- 2022/06/09 06:00 [medline] PHST- 2022/05/22 19:33 [entrez] PHST- 2022/05/19 00:00 [pmc-release] AID - S0734-9750(22)00082-9 [pii] AID - 107986 [pii] AID - 10.1016/j.biotechadv.2022.107986 [doi] PST - ppublish SO - Biotechnol Adv. 2022 Oct;59:107986. doi: 10.1016/j.biotechadv.2022.107986. Epub 2022 May 19.