@article{83d55b1d23f243c59ebc32f4eb47f58e,
title = "Synthetic proteins for COVID-19 diagnostics",
abstract = "There is an urgent need for inexpensive, rapid and specific antigen-based assays to test for vaccine efficacy and detect infection with SARS-CoV-2 and its variants. We have identified a small, synthetic protein (JS7), representing a region of maximum variability within the receptor binding domain (RBD), which binds antibodies in sera from nine patients with PCR-verified COVID-19 of varying severity. Antibodies binding to either JS7 or the SARS-CoV-2 recombinant RBD, as well as those that disrupt binding between a fragment of the ACE2 receptor and the RBD, are proportional to disease severity and clinical outcome. Binding to JS7 was inhibited by linear peptides from the RBD interface with ACE2. Variants of JS7, such as E484K or N501Y, can be quickly synthesized in pure form in large quantities by automated methods. JS7 and related synthetic antigens can provide a basis for specific diagnostics for SARS-CoV-2 infections.",
keywords = "ACE2 interaction, COVID-19 variants, Neutralizing antibodies, Peptide vaccines, Receptor binding domain, S protein epitopes, Structure based design",
author = "Schein, {Catherine H.} and Levine, {Corri B.} and McLellan, {Susan L.F.} and Negi, {Surendra S.} and Werner Braun and Dreskin, {Stephen C.} and Anaya, {Elizabeth S.} and Jurgen Schmidt",
note = "Funding Information: We thank the reviewers for their helpful comments, which have greatly improved this paper. We thank Wendy S. Baker for expert technical assistance, and Wen-Hsian Chen and others in the group at Baylor College of Medicine and Daniel Wrapp (Dartmouth) and the group of Jason McLellan of the University of Texas at Austin for supplying the recombinant proteins (1-4 in Fig. 3) used throughout this work. Peptide and protein syntheses at LANL were supported by LDRD ER funding; sequence analysis was supported by NIAID R01 AI137332 (to WB/CHS). Funding Information: Human sera after infection with COVID-19 (10 samples from 9 patients (Table S1)) were negative for residual virus presence. De-identified clinical samples and clinical data were collected from consented patients under the Observational Protocol for Diseases and Exposures of Public Health Importance (UNMC IRB # 060−20-EP/UTMB-IRB # 20−0031), PI, Dr. Mark Kortepeter, U. Nebraska Medical Center; UTMB site-PI, Dr. Susan McLellan, developed by the Special Pathogens Research Network (SPRN) of the National Emerging and Special Pathogens Training and Education Center (NETEC). NETEC and SPRN are funded by the US Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response (ASPR), CFDA #93.825. Funding Information: We thank the reviewers for their helpful comments, which have greatly improved this paper. We thank Wendy S. Baker for expert technical assistance, and Wen-Hsian Chen and others in the group at Baylor College of Medicine and Daniel Wrapp (Dartmouth) and the group of Jason McLellan of the University of Texas at Austin for supplying the recombinant proteins (1-4 in Fig. 3 ) used throughout this work. Peptide and protein syntheses at LANL were supported by LDRD ER funding; sequence analysis was supported by NIAID R01 AI137332 (to WB/CHS). Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = sep,
doi = "10.1016/j.peptides.2021.170583",
language = "English (US)",
volume = "143",
journal = "Peptides",
issn = "0196-9781",
publisher = "Elsevier Inc.",
}