Synthetic proteins for COVID-19 diagnostics
•Synthetic protein (JS7) and peptides bind serum antibodies of COVID-19 patients.•JS7 represents the interface of SARS-CoV-2 receptor binding domain with ACE2.•Antibody binding to JS7 or recombinant RBD is proportional to disease severity.•RBD/ACE2 interface peptides block antibody binding to JS7 or...
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| Veröffentlicht in: | Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2021-09, Vol.143, p.170583-170583, Article 170583 |
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| container_title | Peptides (New York, N.Y. : 1980) |
| container_volume | 143 |
| creator | Schein, Catherine H. Levine, Corri B. McLellan, Susan L.F. Negi, Surendra S. Braun, Werner Dreskin, Stephen C. Anaya, Elizabeth S. Schmidt, Jurgen |
| description | •Synthetic protein (JS7) and peptides bind serum antibodies of COVID-19 patients.•JS7 represents the interface of SARS-CoV-2 receptor binding domain with ACE2.•Antibody binding to JS7 or recombinant RBD is proportional to disease severity.•RBD/ACE2 interface peptides block antibody binding to JS7 or recombinant RBD.•JS7 variants could be rapidly synthesized for diagnostics or vaccine boosters.
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. |
| doi_str_mv | 10.1016/j.peptides.2021.170583 |
| format | Article |
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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.</description><identifier>ISSN: 0196-9781</identifier><identifier>ISSN: 1873-5169</identifier><identifier>EISSN: 1873-5169</identifier><identifier>DOI: 10.1016/j.peptides.2021.170583</identifier><identifier>PMID: 34087220</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>ACE2 interaction ; Angiotensin-Converting Enzyme 2 - chemistry ; BASIC BIOLOGICAL SCIENCES ; Biological Science ; COVID diagnostic, Synthetic antigens ; COVID-19 ; COVID-19 Serological Testing ; COVID-19 variants ; Humans ; Neutralizing antibodies ; Peptide vaccines ; Peptides - chemistry ; Protein Domains ; Receptor binding domain ; S protein epitopes ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus - chemistry ; Structure based design</subject><ispartof>Peptides (New York, N.Y. : 1980), 2021-09, Vol.143, p.170583-170583, Article 170583</ispartof><rights>2021</rights><rights>Copyright © 2021. Published by Elsevier Inc.</rights><rights>2021 Published by Elsevier Inc. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c498t-d827b9f4023388b5a49ba2efc3e4791e26be3170a4abfef7a9f58db69458edd83</citedby><cites>FETCH-LOGICAL-c498t-d827b9f4023388b5a49ba2efc3e4791e26be3170a4abfef7a9f58db69458edd83</cites><orcidid>0000-0002-8290-2109 ; 0000000282902109 ; 0000000281929940 ; 000000028164921X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.peptides.2021.170583$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34087220$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/servlets/purl/1822799$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Schein, Catherine H.</creatorcontrib><creatorcontrib>Levine, Corri B.</creatorcontrib><creatorcontrib>McLellan, Susan L.F.</creatorcontrib><creatorcontrib>Negi, Surendra S.</creatorcontrib><creatorcontrib>Braun, Werner</creatorcontrib><creatorcontrib>Dreskin, Stephen C.</creatorcontrib><creatorcontrib>Anaya, Elizabeth S.</creatorcontrib><creatorcontrib>Schmidt, Jurgen</creatorcontrib><creatorcontrib>Los Alamos National Lab. (LANL), Los Alamos, NM (United States)</creatorcontrib><title>Synthetic proteins for COVID-19 diagnostics</title><title>Peptides (New York, N.Y. : 1980)</title><addtitle>Peptides</addtitle><description>•Synthetic protein (JS7) and peptides bind serum antibodies of COVID-19 patients.•JS7 represents the interface of SARS-CoV-2 receptor binding domain with ACE2.•Antibody binding to JS7 or recombinant RBD is proportional to disease severity.•RBD/ACE2 interface peptides block antibody binding to JS7 or recombinant RBD.•JS7 variants could be rapidly synthesized for diagnostics or vaccine boosters.
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.</description><subject>ACE2 interaction</subject><subject>Angiotensin-Converting Enzyme 2 - chemistry</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Biological Science</subject><subject>COVID diagnostic, Synthetic antigens</subject><subject>COVID-19</subject><subject>COVID-19 Serological Testing</subject><subject>COVID-19 variants</subject><subject>Humans</subject><subject>Neutralizing antibodies</subject><subject>Peptide vaccines</subject><subject>Peptides - chemistry</subject><subject>Protein Domains</subject><subject>Receptor binding domain</subject><subject>S protein epitopes</subject><subject>SARS-CoV-2</subject><subject>Spike Glycoprotein, Coronavirus - chemistry</subject><subject>Structure based design</subject><issn>0196-9781</issn><issn>1873-5169</issn><issn>1873-5169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vEzEQhi1ERUPhL1QRJyS0qT92_XFBoLRApUo9tHC1vPZs4yixF9up1H9fr7at4NTTHOaZd96ZF6FTglcEE362XY0wFu8gryimZEUE7iR7gxZECtZ0hKu3aIGJ4o0Skhyj9zlvMcZtq-Q7dMxaLAWleIG-3DyEsoHi7XJMsYAPeTnEtFxf_7k8b4haOm_uQswVyB_Q0WB2GT4-1RP0-8fF7fpXc3X983L9_aqxVb00TlLRq6HFlDEp-860qjcUBsugFYoA5T2w6te0ph9gEEYNnXQ9V20nwTnJTtDXWXc89HtwFkJJZqfH5PcmPehovP6_E_xG38V7LQmXjIsq8GkWmHzrbH0Bu7ExBLBFE0mpUKpCn5-2pPj3ALnovc8WdjsTIB6yph0TnFFOcEX5jNoUc04wvHghWE9x6K1-jkNPceg5jjp4-u8lL2PP_6_AtxmA-s97D2lyC8GC82ky66J_bccjYq2e0w</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>Schein, Catherine H.</creator><creator>Levine, Corri B.</creator><creator>McLellan, Susan L.F.</creator><creator>Negi, Surendra S.</creator><creator>Braun, Werner</creator><creator>Dreskin, Stephen C.</creator><creator>Anaya, Elizabeth S.</creator><creator>Schmidt, Jurgen</creator><general>Elsevier Inc</general><general>Elsevier</general><general>Published by Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OIOZB</scope><scope>OTOTI</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8290-2109</orcidid><orcidid>https://orcid.org/0000000282902109</orcidid><orcidid>https://orcid.org/0000000281929940</orcidid><orcidid>https://orcid.org/000000028164921X</orcidid></search><sort><creationdate>20210901</creationdate><title>Synthetic proteins for COVID-19 diagnostics</title><author>Schein, Catherine H. ; Levine, Corri B. ; McLellan, Susan L.F. ; Negi, Surendra S. ; Braun, Werner ; Dreskin, Stephen C. ; Anaya, Elizabeth S. ; Schmidt, Jurgen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c498t-d827b9f4023388b5a49ba2efc3e4791e26be3170a4abfef7a9f58db69458edd83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>ACE2 interaction</topic><topic>Angiotensin-Converting Enzyme 2 - chemistry</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>Biological Science</topic><topic>COVID diagnostic, Synthetic antigens</topic><topic>COVID-19</topic><topic>COVID-19 Serological Testing</topic><topic>COVID-19 variants</topic><topic>Humans</topic><topic>Neutralizing antibodies</topic><topic>Peptide vaccines</topic><topic>Peptides - chemistry</topic><topic>Protein Domains</topic><topic>Receptor binding domain</topic><topic>S protein epitopes</topic><topic>SARS-CoV-2</topic><topic>Spike Glycoprotein, Coronavirus - chemistry</topic><topic>Structure based design</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schein, Catherine H.</creatorcontrib><creatorcontrib>Levine, Corri B.</creatorcontrib><creatorcontrib>McLellan, Susan L.F.</creatorcontrib><creatorcontrib>Negi, Surendra S.</creatorcontrib><creatorcontrib>Braun, Werner</creatorcontrib><creatorcontrib>Dreskin, Stephen C.</creatorcontrib><creatorcontrib>Anaya, Elizabeth S.</creatorcontrib><creatorcontrib>Schmidt, Jurgen</creatorcontrib><creatorcontrib>Los Alamos National Lab. (LANL), Los Alamos, NM (United States)</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV - Hybrid</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Peptides (New York, N.Y. : 1980)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schein, Catherine H.</au><au>Levine, Corri B.</au><au>McLellan, Susan L.F.</au><au>Negi, Surendra S.</au><au>Braun, Werner</au><au>Dreskin, Stephen C.</au><au>Anaya, Elizabeth S.</au><au>Schmidt, Jurgen</au><aucorp>Los Alamos National Lab. (LANL), Los Alamos, NM (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthetic proteins for COVID-19 diagnostics</atitle><jtitle>Peptides (New York, N.Y. : 1980)</jtitle><addtitle>Peptides</addtitle><date>2021-09-01</date><risdate>2021</risdate><volume>143</volume><spage>170583</spage><epage>170583</epage><pages>170583-170583</pages><artnum>170583</artnum><issn>0196-9781</issn><issn>1873-5169</issn><eissn>1873-5169</eissn><abstract>•Synthetic protein (JS7) and peptides bind serum antibodies of COVID-19 patients.•JS7 represents the interface of SARS-CoV-2 receptor binding domain with ACE2.•Antibody binding to JS7 or recombinant RBD is proportional to disease severity.•RBD/ACE2 interface peptides block antibody binding to JS7 or recombinant RBD.•JS7 variants could be rapidly synthesized for diagnostics or vaccine boosters.
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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>34087220</pmid><doi>10.1016/j.peptides.2021.170583</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-8290-2109</orcidid><orcidid>https://orcid.org/0000000282902109</orcidid><orcidid>https://orcid.org/0000000281929940</orcidid><orcidid>https://orcid.org/000000028164921X</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Peptides (New York, N.Y. : 1980), 2021-09, Vol.143, p.170583-170583, Article 170583 |
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| subjects | ACE2 interaction Angiotensin-Converting Enzyme 2 - chemistry BASIC BIOLOGICAL SCIENCES Biological Science COVID diagnostic, Synthetic antigens COVID-19 COVID-19 Serological Testing COVID-19 variants Humans Neutralizing antibodies Peptide vaccines Peptides - chemistry Protein Domains Receptor binding domain S protein epitopes SARS-CoV-2 Spike Glycoprotein, Coronavirus - chemistry Structure based design |
| title | Synthetic proteins for COVID-19 diagnostics |
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