Core Viewpoint - The article discusses the significant role of respiratory viruses, particularly coronaviruses and influenza viruses, in global pandemics and their impact on public health, emphasizing the importance of understanding immune responses and potential antiviral strategies [1][2]. Group 1: Immune Response and Interferon - The innate immune response, including interferons (IFN) and interferon-stimulated genes (ISG), serves as the first line of defense against viral attacks [2]. - Delayed or impaired type I interferon (IFN-I) responses are notable characteristics of severe COVID-19 and influenza infections, with 3.5% of life-threatening COVID-19 patients exhibiting harmful mutations in interferon system genes [2]. - In critical COVID-19 patients, nearly 15% have been found to possess neutralizing antibodies against their own interferons, indicating a significant immune response issue [2]. Group 2: GALNT2 and Antiviral Mechanism - A recent study published in Nature Microbiology identifies GALNT2 as an ISG with broad antiviral activity, establishing it as a crucial defense factor against respiratory virus infections [3][9]. - GALNT2 inhibits the replication of various coronaviruses and influenza viruses, promoting viral clearance and reducing disease severity through O-glycosylation of viral proteins [6][9]. - The mechanism involves GALNT2 modifying the spike protein of SARS-CoV-2, preventing its cleavage by proteases, thus blocking virus-host cell fusion [6][7]. Group 3: Genetic Insights and Implications - Analysis of human genetic data reveals that individuals with GALNT2 gene mutations that impair antiviral function have a significantly higher risk of hospitalization after SARS-CoV-2 infection [8]. - The findings deepen the understanding of host-virus interactions and provide new targets for developing broad-spectrum antiviral strategies against respiratory pathogens [10].

Core Viewpoint - The article discusses the emergence of Severe Fever with Thrombocytopenia Syndrome (SFTS) caused by the Dabie bandavirus (SFTSV), highlighting its public health challenges and the development of a novel nanobody cocktail for potential treatment [2][8]. Group 1: Disease Overview - SFTS is caused by SFTSV, transmitted by ticks, and has been prevalent in regions such as Anhui, Jiangsu, Zhejiang, and Shandong in China, as well as in Japan and South Korea [2]. - Symptoms include fever and thrombocytopenia, with severe cases leading to multi-organ failure and a mortality rate ranging from 6% to 30% [2]. Group 2: Research Development - A research team led by Professor Wu Xilin from Nanjing University published a study on a cocktail of nanobodies designed to protect against SFTSV in preclinical models [3]. - The study utilized a "sequential heterologous immunization" strategy to isolate and identify nanobodies targeting SFTSV from llamas, leading to the design of a nanobody cocktail (Nb261 + Nb318) [6]. Group 3: Treatment Efficacy - The nanobody cocktail demonstrated complete neutralization of various SFTSV subtypes in vitro and showed excellent therapeutic effects in mouse and aged ferret models, achieving a 100% survival rate, complete viral clearance, and significant improvement in thrombocytopenia and tissue damage [7]. - This research represents the first systematic validation of mixed nanobodies for treating SFTSV in large animal models, providing unprecedented evidence for developing safe and effective SFTSV treatments [8]. Group 4: Future Directions - The research integrates multiple fields, including structural biology, immunology, virology, and translational medicine, showcasing a novel strategy for broad-spectrum antiviral development [9]. - The research team has initiated preclinical studies on pharmacokinetics, toxicology, and process scaling for the Nb261 + Nb318 cocktail, aiming to provide new preventive and therapeutic options for SFTS [9].