[HTML][HTML] Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor

X Chen, R Li, Z Pan, C Qian, Y Yang, R You… - Cellular & molecular …, 2020 - nature.com
X Chen, R Li, Z Pan, C Qian, Y Yang, R You, J Zhao, P Liu, L Gao, Z Li, Q Huang, L Xu…
Cellular & molecular immunology, 2020nature.com
According to the World Health Organization (WHO) newly updated situation report on March
18th, 2020, the coronavirus disease 2019 (COVID-19) pandemic has confirmed 191,127
cases and claimed 7807 deaths worldwide. 1 The etiological agent of COVID-19 has been
identified as a novel coronavirus, the severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2), belonging to Sarbecovirus subgenus (genus Betacoronavirus, family
Coronaviridae) and showing 79.6 and 96.2% sequence identity in nucleotide to SARS-CoV …
According to the World Health Organization (WHO) newly updated situation report on March 18th, 2020, the coronavirus disease 2019 (COVID-19) pandemic has confirmed 191,127 cases and claimed 7807 deaths worldwide. 1 The etiological agent of COVID-19 has been identified as a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belonging to Sarbecovirus subgenus (genus Betacoronavirus, family Coronaviridae) and showing 79.6 and 96.2% sequence identity in nucleotide to SARS-CoV and a bat coronavirus (BatCoV RaTG13), respectively. 2-4 Like SARS-CoV infection, a substantial fraction of COVID-19 patients exhibits severe respiratory symptoms and has to be hospitalized in intensive care unit. 5-8 Although the mortality rate of COVID-19 is significantly lower than that of SARS-CoV infection, SARS-CoV-2 shows much higher human-to-human transmission rate, rapidly leading to a global pandemic declared by WHO on March 11th, 2020. 9 Currently, there are no approved prophylactic vaccines or therapeutic drugs that are specific to COVID-19. Blocking monoclonal antibodies (mAbs), due to their extraordinary antigen specificity, are one of the best candidates for neutralizing virus infection. 10, 11 Therefore, identifying and cloning blocking mAbs that can specifically target surface viral proteins to block the viral entry to host cells is a very attractive approach for preventing and treating COVID-19, in particular when effective vaccines and therapeutics are unavailable in the outbreak of the COVID-19 pandemic. We then sought to identify and clone blocking mAbs from the memory B cell repertoire of recently recovered COVID-19 patients to prevent the entry of COVID-19 virus to the host cells. Similar to SARS-CoV, SARS-CoV-2 also utilizes highly glycosylated homotrimeric spike (S) protein for receptor binding and virus entry. 3, 12-15 The S protein of SARS-CoV-2 consists of two subunits, S1 and S2. To engage host cell receptor human angiotensinconverting enzyme 2 (hACE2), shared by both SARS-CoV and SARS-CoV-2, S protein undergoes dramatic conformational changes to expose the RBD and key residues for receptor binding. S protein is metastable, and binding of RBD to hACE2 receptor likely leads to the shedding of S1 protein from S2 protein, thus promoting S2-mediated virus-host membrane fusion and virus entry. 16-18 Given the critical role of the RBD in initiating invasion of SARS-CoV-2 into host cells, it becomes a vulnerable target for neutralizing antibodies. Thus far, the human mAbs specifically target the SARS-CoV-2 RBD-hACE2 interaction have not been reported, and a monoclonal antibody targeting S1 made from immunized transgenic mice expressing human Ig variable heavy and light chains has been recently shown to neutralize both SARS-CoV-2 and SARS-CoV infection, but by an unknown mechanism that is independent of the blockade of RBD-hACE2 interaction. 19 Prior to cloning SARS-CoV-2 RBD-specific human mAbs, we first examined whether patients recently recovered from COVID-19 had mounted anti-SARS-CoV-2 S1 protein IgG antibodies in sera. Among 26 recovered COVID-19 patients, we found that the majority of these recruited patients were able to produce high titers of SARS-CoV-2 S1-specific IgG antibodies and only three patients mounted relatively lower anti-S1 IgG responses, by enzyme-linked immunosorbent assay (ELISA)(Fig. 1 a). Consistently, we also found that SARS-CoV-2 RBD-specific IgG antibodies were present in sera of all patients by ELISA (Fig. 1 b). Next, we sought to investigate whether RBD-specific antibodies in patient serum can block the …
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