A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation

Kang, Shiyang; Yang, Mei; He, Songtao; Wang, Yueming; Chen, Xiaoxue; Chen, Yao-Qing; Hong, Zhongsi; Liu, Jing; Jiang, Guanmin; Chen, Qiuyue; Zhou, Ziliang; Zhou, Zhechong; Huang, Zhenguo; Huang, Xi; He, Huanhuan; Zheng, Wenwei; Liao, Hua‐Xin; Xiao, Fei; Shan, Hong; Chen, Shoudeng

doi:10.1038/s41467-021-23036-9

Cited by 78 publications

(64 citation statements)

References 38 publications

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“…Patients with severe COVID-19 showed complement activation and high concentrations of C5a and MAC, suggesting that dysregulation of the complement pathway may participate in CSS and severe COVID-19 complications [ 143 – 147 ]. Notably, mechanistic studies showed the S or nucleocapsid protein of SARS-CoV-2 can activate the complement pathway [ 148 , 149 ]. Based on the apparent involvement of complement in COVID-19, clinical studies have been initiated for several Abs, including avdoralimab, eculizumab, and vilobelimab (Table 3 ).…”

Section: Therapeutic Absmentioning

confidence: 99%

Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

et al. 2022

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The coronavirus disease 2019 (COVID-19) pandemic is an exceptional public health crisis that demands the timely creation of new therapeutics and viral detection. Owing to their high specificity and reliability, monoclonal antibodies (mAbs) have emerged as powerful tools to treat and detect numerous diseases. Hence, many researchers have begun to urgently develop Ab-based kits for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ab drugs for use as COVID-19 therapeutic agents. The detailed structure of the SARS-CoV-2 spike protein is known, and since this protein is key for viral infection, its receptor-binding domain (RBD) has become a major target for therapeutic Ab development. Because SARS-CoV-2 is an RNA virus with a high mutation rate, especially under the selective pressure of aggressively deployed prophylactic vaccines and neutralizing Abs, the use of Ab cocktails is expected to be an important strategy for effective COVID-19 treatment. Moreover, SARS-CoV-2 infection may stimulate an overactive immune response, resulting in a cytokine storm that drives severe disease progression. Abs to combat cytokine storms have also been under intense development as treatments for COVID-19. In addition to their use as drugs, Abs are currently being utilized in SARS-CoV-2 detection tests, including antigen and immunoglobulin tests. Such Ab-based detection tests are crucial surveillance tools that can be used to prevent the spread of COVID-19. Herein, we highlight some key points regarding mAb-based detection tests and treatments for the COVID-19 pandemic.

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Section: Therapeutic Absmentioning

confidence: 99%

Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

et al. 2022

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“…Several neutralizing antibodies targeting the RBD of S protein are being analyzed and evaluated clinically [ 11 , 12 ]. The N terminal-domain (NTD) of S protein also contains immunoprotective epitopes, the most immunodominant of which elicits the production of antibody 4A8, a mAb with high neutralizing potency against the NTD of SARS-CoV-2 [ 13 , 14 ].…”

Section: Neutralizing Antibodiesmentioning

confidence: 99%

“…Antibodies targeting the viral nucleocapsid (N) protein—which may mediate viral genome expression and assembly—have been isolated from convalescent sera of COVID-19 patients in the early recovery phase; in contrast, anti-S protein antibodies dominate late-phase sera [ 14 , 22 , 23 ]. A recent study highlighted a particular anti-N-protein nAb, nCoV396, which inhibited N-protein–MASP-2 interaction [ 14 ], thus blocking N-protein-mediated complement hyperactivation and combatting the pro-inflammatory state characterizing COVID-19 [ 14 ]. Further work is required to elucidate the full prophylactic and therapeutic potential of these Abs.…”

Section: Neutralizing Antibodiesmentioning

confidence: 99%

Effect of SARS-CoV-2 Mutations on the Efficacy of Antibody Therapy and Response to Vaccines

et al. 2021

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SARS-CoV-2 causes severe acute respiratory syndrome, which has led to significant morbidity and mortality around the world. Since its emergence, extensive prophylactic and therapeutic countermeasures have been employed to successfully prevent the spread of COVID-19. Extensive work has been undertaken on using monoclonal antibody therapies, mass vaccination programs, and antiviral drugs to prevent and treat COVID-19. However, since antiviral drugs could take years to become widely available, immunotherapy and vaccines currently appear to be the most feasible option. In December 2020, the first vaccine against SARS-CoV-2 was approved by the World Health Organization (WHO) and, subsequently, many other vaccines were approved for use by different international regulators in different countries. Most monoclonal antibodies (mAbs) and vaccines target the SARS-CoV-2 surface spike (S) protein. Recently, mutant (or variant) SARS-CoV-2 strains with increased infectivity and virulence that evade protective host antibodies present either due to infection, antibody therapy, or vaccine administration have emerged. In this manuscript, we discuss the different monoclonal antibody and vaccine therapies available against COVID-19 and how the efficacy of these therapies is affected by the emergence of variants of SARS-CoV-2. We also discuss strategies that might help society cope with variants that could neutralize the effects of immunotherapy and escape the protective immunity conferred by vaccines.

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“…Most recently, Ma et al showed that NP binds the Gasdermin D linker region and hinders Gasdermin D cleavage by caspase-1 in monocytes, leading to the inhibition of host cell pyroptosis [9]. Kang et al isolated a high-affinity anti-NP mAb from a convalescent COVID-19 patient and found that the binding of the mAb to the RBD of NP compromised the induction of complement hyperactivation by NP, a risk factor for the morbidity and mortality of COVID-19 patients [10]. Interestingly, viral NP and the RNA genome are detectable in blood specimens of SARS-CoV-2-infected patients, and the levels correlate with mortality in COVID-19 ICU patients [11,12].…”

Section: Introductionmentioning

confidence: 99%

Monoclonal Antibodies against Nucleocapsid Protein of SARS-CoV-2 Variants for Detection of COVID-19

Chen

et al. 2021

IJMS

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Mitigation strategies of the coronavirus disease 2019 (COVID-19) pandemic have been greatly hindered by the continuous emergence of SARS-CoV-2 variants. New sensitive, rapid diagnostic tests for the wide-spectrum detection of viral variants are needed. We generated a panel of 41 monoclonal antibodies against the SARS-CoV-2 nucleocapsid protein (NP) by using mice hybridoma techniques. Of these mAbs, nine exhibited high binding activities and were applied in latex-based lateral flow immunoassays (LFIAs). The LFIAs utilizing NP-mAb-7 and -40 had the best sensitivity and lowest limit of detection: 8 pg for purified NP and 625 TCID50/mL for the authentic virus (hCoV-19/Taiwan/4/2020). The specificity tests showed that the NP-mAb-40/7 LFIA strips did not cross-react with five human coronavirus strains or 20 other common respiratory pathogens. Importantly, we found that 10 NP mutants, including alpha (B.1.1.7), beta (B.1.351), gamma (P.1), and delta (B.1.617.2) variants, could be detected by NP-mAb-40/7 LFIA strips. A clinical study (n = 60) of the NP-mAb-40/7 LFIA strips demonstrated a specificity of 100% and sensitivity of 90% in infected individuals with cycle threshold (Ct) values < 29.5. These anti-NP mAbs have strong potential for use in the clinical detection of SARS-CoV-2 infection, whether the virus is wild-type or a variant of concern.

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A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation

Cited by 78 publications

References 38 publications

Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

Effect of SARS-CoV-2 Mutations on the Efficacy of Antibody Therapy and Response to Vaccines

Monoclonal Antibodies against Nucleocapsid Protein of SARS-CoV-2 Variants for Detection of COVID-19

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