A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site.

Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but the variability of RBS epitopes hampers broad neutralization of multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an RBS antibody with a germline VH gene that potently neutralized SARS-related coronaviruses, including SARS-CoV and SARS-CoV-2 variants. X-ray crystallography revealed coordinated recognition by the heavy chain of non-RBS conserved sites and the light chain of RBS with a binding angle mimicking the angiotensin-converting enzyme 2 (ACE2) receptor. The minimum footprints in the hypervariable region of RBS contributed to the breadth of neutralization, which was enhanced by immunoglobulin G3 (IgG3) class switching. The coordinated binding resulted in broad neutralization of SARS-CoV and emerging SARS-CoV-2 variants of concern. Low-dose therapeutic antibody treatment in hamsters reduced the virus titers and morbidity during SARS-CoV-2 challenge. The structural basis for broad neutralizing activity may inform the design of a broad spectrum of therapeutics and vaccines.

Pathogenic characterization of a cervical lymph node derived from a patient with Kawasaki disease.

Kawasaki disease (KD) is the most common cause of multisystem vasculitis in childhood. Although cervical lymphadenitis is one of the major symptoms in KD, lymph node biopsy is rarely performed, because KD is usually diagnosed by clinical symptoms. A cervical lymph node biopsy was taken from a girl aged 1 year and 8 months who had suspected lymphoma, but she was diagnosed with KD after the biopsy. The cervical lymph node specimen was analyzed with multivirus real-time PCR that can detect >160 viruses, and unbiased direct sequencing with a next-generation DNA sequencer to detect potential pathogens in the lymph node. Histologically, focal necrosis with inflammatory cell infiltration, including neutrophils and macrophages, was observed in the marginal zone of the cervical lymph node, which was compatible with the acute phase of KD. Multivirus real-time PCR detected a low copy number of torque teno virus in the sample. Comprehensive direct sequencing of the cervical lymph node biopsy sample sequenced more than 8 million and 3 million reads from DNA and RNA samples, respectively. Bacterial genomes were detected in 0.03% and 1.79% of all reads in DNA and RNA samples, respectively. Although many reads corresponded to genomes of bacterial environmental microorganisms, Streptococcus spp. genome was detected in both DNA (77 reads) and RNA (2,925 reads) samples. Further studies are required to reveal any association of microbial or viral infection with the pathogenesis of KD.