Influenza A virus pandemics pose a persistent global health threat, and emerging antiviral resistance underscores the critical importance of developing novel broad-spectrum therapeutic agents. Building on licorice’s (Glycyrrhiza spp.) historical use in traditional Chinese medicine for respiratory infections—as documented in the Chinese Guidelines for Diagnosis and Treatment of Influenza—and its demonstrated anti-SARS-CoV-2 activity, we identified licoflavone B as a potent anti-influenza agent, bridging ethnopharmacological knowledge with mechanistic validation. In this study, we identified licoflavone B, a natural flavonoid derived from licorice (Glycyrrhiza spp.), as a potent inhibitor of diverse influenza viruses, including multiple influenza A subtypes and type B virus. Mechanistic studies revealed that licoflavone B selectively targets the viral RNA-dependent RNA polymerase (RdRp), effectively suppressing viral replication. The compound exhibits a favorable selectivity index (SI = 14.9–29.9), indicating a promising therapeutic window. Molecular docking simulations identified potential binding interactions between licoflavone B and regions of the RdRp complex, which were further validated by dose-dependent inhibition of viral nucleoprotein (NP) and polymerase subunit PB2 expression in Western blot and immunofluorescence assays. In addition, licoflavone B maintained broad-spectrum antiviral activity against multiple influenza strains, including H1N1 (A/Puerto Rico/8/34), H3N2 (A/Darwin/9/2021), and a clinical influenza B isolate (B/Beijing/ZYY-B18/2018). These findings position licoflavone B as a promising lead compound for developing next-generation, broad-spectrum antiviral therapies against influenza and potentially other viruses.

Rift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus that can cause substantial morbidity and mortality in livestock and humans, for which there are no currently available licensed human therapeutics or vaccines. Therefore, the development of safe and effective antivirals is both necessary and urgent. The Gc protein is the primary target of the neutralizing antibody response related to Rift Valley fever virus. Here, we report one Gc-specific neutralizing antibody (NA137) isolated from an alpaca and one bispecific antibody (E2-NA137), the protective efficacies of which we evaluated in A129 mice. In this prophylactic study, the survival rates of the NA137 and E2-NA137 groups were both 80%, and in the treatment study, the survival rates were 20% and 60%, respectively. Altogether, our results emphasize that NA137 and E2-NA137 provide a potential approach for treating RVFV either prophylactically or therapeutically.

Human adenovirus type 4 (HAdV-4) is a predominant serotype causing acute respiratory infections, for which no antibody drugs have been clinically approved to date, resulting in an urgent unmet medical need. This study aimed to identify highly potent neutralizing antibodies by dissecting the B cell immune response after infection, thereby laying a foundation for vaccine design and antiviral therapy. Peripheral blood mononuclear cells (PBMCs) were isolated from a convalescent patient who exhibited the most robust neutralizing antibody titers among 16 HAdV-4 convalescent volunteers. A total of 2710 B cells were isolated from the peripheral blood of this patient, and the characteristics of B cell subsets and B cell receptor (BCR) repertoires were comprehensively analyzed by integrating scRNA-seq and scVDJ-seq technologies. Candidate antibodies were subsequently selected for a series of functional and mechanistic validations based on the characteristics of BCRs and origination. Transcriptomic profiling classified memory B cells into three functionally heterogeneous subpopulations designated as MB sub1, sub2 and sub3. Combined with the characteristics of BCR, 92 selected antibodies from sub2 and sub3 were synthesized for further functional validation. Three potent neutralizing antibodies were successfully identified, among which 1QH7 demonstrated potentially potent virus neutralization capability in vitro and conferred robust in vivo protection in the Stat1-deficient mouse model. We further employed AlphaFold 3 to predict the complex structure of 1QH7 with the HAdV-4 Hexon protein and validated the key binding residues through site-directed mutagenesis. Additionally, the study elucidated the viral neutralization mechanism mediated by TRIM21. We established an efficient antibody screening strategy based on integration of scRNA-seq and scVDJ-seq and isolated a potent neutralizing antibody, 1QH7. This study lays a solid foundation for the rapid pathogen-bait-free, cell subset-guided screening antibody route for novel emerging infectious disease outbreaks.