Dengue fever is an arbovirus disease caused by infection with the dengue virus (DENV). Half of the world’s population lives under the threat of dengue fever, however, researchers have yet to develop any drugs that are clinically applicable to this infection. Micafungin is a member of the echinocandins family of anti-fungal drugs, capable of blocking the synthesis of β-1,3-D-glucan in the walls of fungal cells. Previous studies have demonstrated the effectiveness of Micafungin against infections of enterovirus 71 (EV71) and chikungunya virus (CHIKV). This is the first study demonstrating the effectiveness of micafungin in inhibiting the cytopathic effects of dengue virus serotype 2 (DENV-2) in a dose-dependent manner. Time-of-addition assays verified the inhibitory effects of micafungin in pre-treated, co-treated, and full-treatment groups. Binding and entry assays also demonstrated the effectiveness of micafungin in the early stage of DENV-2 infection. The virucidal efficacy of micafungin appears to lie in its ability to destroy the virion. Molecular docking assays revealed the binding of micafungin to the envelope protein of DENV-2, thereby revealing the mechanism by which micafungin affects the early stage of DENV infection and the stability of DENV. Two other micafungin analogs, caspofungin and anidulafungin, were also shown to have the antiviral effects on DENV-2. Finally, immunofluorescence assay (IFA) and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) confirmed the broad anti-DENV ability of micafungin against dengue virus serotypes 1, 3, and 4 (DENV-1, DENV-3, and DENV-4). Taken together, these results demonstrate the potential of micafungin and its analogs as candidates for the development of broad-spectrum treatments for DENV infection.

Background: Understanding the extent of cross-protection conferred by the historic smallpox vaccination and the immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) after the 2022 global mpox outbreak is essential to inform current prevention strategies. In this study, we assessed the seropositivity and neutralizing capacities of the vaccinia virus (VACV)- and monkeypox virus (MPXV)-specific antibodies in 260 Taiwanese patients. Methods: We analyzed serum samples from 260 individuals in Taiwan, stratified by their birth year, before or after 1979, the year of smallpox vaccination cessation. ELISA and plaque reduction neutralization tests were conducted to assess VACV- and MPXV-specific antibody responses. Furthermore, we evaluated an additional cohort of MVA-BN vaccines (n = 9) before and after vaccination. Results: Over 80% of individuals born before 1979 retained VACV-reactive antibodies, with 84% of this seropositive subgroup exhibiting neutralizing activity. We detected cross-reactive MPXV antibodies in 69% of individuals who were VACV-seropositive; however, only 65% had MPXV-neutralizing capacity, with titers significantly lower than those against VACV. MVA-BN vaccination enhanced VACV and MPXV antibody levels; however, MPXV-neutralizing titers remained low, particularly in individuals without prior smallpox immunization. Conclusion: Historical smallpox vaccination induces long-lasting humoral immunity, and a correlation between VACV and MPXV antibody levels further suggests that it provides some degree of cross-protection against MPXV infection. MVA-BN boosted orthopoxvirus immunity; however, it may be limited in MPXV neutralization in vaccine-naïve populations. These findings offer useful insights for future mpox vaccination strategies and public health planning in regions with varying smallpox vaccination histories.

Beyond direct neutralization, antibodies clear SARS-CoV-2 by triggering antibody-dependent cellular cytotoxicity (ADCC), which guides natural killer (NK) cells to eliminate infected cells. To understand ADCC’s role in COVID-19, we analyze samples from primary patients and find that plasma ADCC activity correlated with a slower rate of viral clearance. To explore this mechanism, we isolate a monoclonal antibody with potent ADCC activity against SARS-CoV-2 variants. In infected mice, this antibody activates an antiviral transcriptional program in the lungs that suppresses viral RNA synthesis. Spatial transcriptomic analysis of mice treated with ADCC-mediating antibodies reveals that low expression of cytolytic NK cell markers and NK cell cluster-associated gene pathways are linked to pulmonary viral clearance. Furthermore, human peripheral NK cells activate pre-existing NK cell clusters when engaging the ADCC antibody. Our findings demonstrate that ADCC-mediating antibodies recruit NK subsets with low baseline cytolytic signatures to facilitate effective viral clearance.