Key Points SARS-CoV-2 protease (Mpro) stimulates a strong Ab response. Detection of Mpro Abs in serum or saliva can provide a new diagnostic tool. 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.

中文翻译：

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可以在 COVID-19 血清阳性个体的血清和唾液中检测到 SARS-CoV-2 半胱氨酸样蛋白酶抗体

要点 SARS-CoV-2 蛋白酶 (Mpro) 会刺激强烈的抗体反应。检测血清或唾液中的 Mpro Abs 可以提供一种新的诊断工具。目前，需要可靠的测试来识别感染了 SARS-CoV-2 的个体，即使感染是无症状的。迄今为止，针对 SARS-CoV-2 特异性抗体的绝大多数血清学检测都是基于对病毒刺突糖蛋白（中和抗体的主要目标）或已知的病毒核衣壳蛋白的抗体的血清检测。在其他冠状病毒中具有高度免疫原性。可以想象，暴露于感染细胞释放的 Ags 可以刺激可能与组织损伤相关的 Ab 反应，因此，它们可能具有一些作为预后指标的价值。我们讨论了其他非结构病毒蛋白是否 未掺入感染性病毒颗粒，特别是病毒半胱氨酸样蛋白酶，也可能是有效的免疫原。使用 ELISA 测试，包被体外产生的几种 SARS-CoV-2 蛋白，我们描述了 COVID-19 患者对来自 SARS-CoV-2 的 Cys 样蛋白酶产生高滴度 IgG、IgM 和 IgA Ab 反应，也称为3CLpro 或 Mpro，可用于识别冠状病毒血清学阳性的个体。在这些检测中，较高的抗体滴度与更严重的疾病相关，并且没有发现针对先前β冠状病毒的交叉反应性抗体。值得注意的是，还可以在唾液中检测到 Mpro 和其他 SARS-CoV-2 Ag 的特异性 IgG 抗体。总之，Mpro 是感染患者体内的一种有效抗原，可用于血清学检测，它在唾液中的检测可能是快速、