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SARS-CoV-2 Cysteine-like Protease Antibodies Can Be Detected in Serum and Saliva of COVID-19-Seropositive Individuals.

Abstract
Currently, there is a need for reliable tests that allow identification of individuals that have been infected with SARS-CoV-2 even if the infection was asymptomatic. To date, the vast majority of the serological tests for SARS-CoV-2-specific Abs are based on serum detection of Abs to either the viral spike glycoprotein (the major target for neutralizing Abs) or the viral nucleocapsid protein that is known to be highly immunogenic in other coronaviruses. Conceivably, exposure of Ags released from infected cells could stimulate Ab responses that might correlate with tissue damage and, hence, they may have some value as a prognostic indicator. We addressed whether other nonstructural viral proteins, not incorporated into the infectious viral particle, specifically the viral cysteine-like protease, might also be potent immunogens. Using ELISA tests, coating several SARS-CoV-2 proteins produced in vitro, we describe that COVID-19 patients make high titer IgG, IgM, and IgA Ab responses to the Cys-like protease from SARS-CoV-2, also known as 3CLpro or Mpro, and it can be used to identify individuals with positive serology against the coronavirus. Higher Ab titers in these assays associated with more-severe disease, and no cross-reactive Abs against prior betacoronavirus were found. Remarkably, IgG Abs specific for Mpro and other SARS-CoV-2 Ags can also be detected in saliva. In conclusion, Mpro is a potent Ag in infected patients that can be used in serological tests, and its detection in saliva could be the basis for a rapid, noninvasive test for COVID-19 seropositivity.
AuthorsPedro Martínez-Fleta, Arantzazu Alfranca, Isidoro González-Álvaro, Jose M Casasnovas, Daniel Fernández-Soto, Gloria Esteso, Yaiza Cáceres-Martell, Sofía Gardeta, Celia López-Sanz, Salomé Prat, Tamara Mateu-Albero, Ligia Gabrie, Eduardo López-Granados, Francisco Sánchez-Madrid, Hugh T Reyburn, José M Rodríguez Frade, Mar Valés-Gómez
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 205 Issue 11 Pg. 3130-3140 (12 01 2020) ISSN: 1550-6606 [Electronic] United States
PMID33148714 (Publication Type: Clinical Trial, Journal Article)
CopyrightCopyright © 2020 by The American Association of Immunologists, Inc.
Chemical References
  • Antibodies, Viral
  • Nucleocapsid Proteins
  • Cysteine Proteases
Topics
  • Adult
  • Aged
  • Antibodies, Viral (blood)
  • Betacoronavirus (metabolism)
  • COVID-19
  • Coronavirus Infections (blood)
  • Cysteine Proteases (metabolism)
  • Female
  • HEK293 Cells
  • Humans
  • Male
  • Middle Aged
  • Nucleocapsid Proteins (metabolism)
  • Pandemics
  • Pneumonia, Viral (blood)
  • SARS-CoV-2
  • Saliva (metabolism)

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