Significance SARS-CoV-2 continues to evolve through emerging variants, more frequently observed with higher transmissibility. Despite the wide application of vaccines and antibodies, the selection pressure on the Spike protein may lead to further evolution of variants that include mutations that can evade immune response. To catch up with the virus’s evolution, we introduced a deep learning approach to redesign the complementarity-determining regions (CDRs) to target multiple virus variants and obtained an antibody that broadly neutralizes SARS-CoV-2 variants.

Epstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. Here, we isolate EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralizes EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provides protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis reveals that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identify a potent and protective neutralizing antibody capable of reducing the EBV load. The novel vulnerable site represents an attractive target that is potentially important for antibody and vaccine intervention against EBV infection.

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As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines.

Background: The role of microRNA-133a (miR-133a) in non-small cell lung cancers (NSCLCs) is controversial. Thus, we conducted a comprehensive study based on meta-analysis and The Cancer Genome Atlas (TCGA) database. Methods: Publications were searched in both English and Chinese databases, and meta-analysis was performed using Stata 12.0. The clinical value of miR-133a in NSCLC was investigated by collecting and calculating data from the TCGA database, and the statistical analysis was performed in R 3.5.0. Results: 5 studies with 364 cases were included in this meta-analysis. The combined pooled result showed that high expression of miR-133a was associated with a favorable survival outcome in NSCLC patients (hazard ratio 0.561, 95% confidence interval 0.396-0.794, p = 0.001). Meanwhile, a total of 984 NSCLC patients were extracted from the TCGA database. Results showed an area under the ROC curve value for miR-133a-3p of 0.902, and the expression of miR-133a-3p was linked with clinicopathologic parameters of NSCLC (p < 0.05), including sex, age, social status, and lymph node metastasis. Conclusion: Our study indicated that miR-133a might act as a tumor suppressor and be a valuable independent prognostic and diagnostic biomarker for NSCLC, and NSCLC patients with high expression of miR-133 might have a better prognosis.