Metformin as antiviral therapy protects hyperglycemic and diabetic patients

作者：Xi Wang, Xiaojie Zheng, Hong‐Han Ge, Ning Cui, Ling Lin, Ming Yue, Chuanlong Zhu, Qi Zhou, Peixin Song, Xing Shang, Rui Wang, Zhen Wang, Zhiyou Wang, Yun-Fa Zhang, Xiaohong Yin, Linsheng Yang, Hong Su, Hao Li, Wei Liu · 发表于：mBio · 年份：2025 · DOI：10.1128/mbio.00634-25 · 被引用次数：4 · 研究领域：Viral Infections and Vectors、Mosquito-borne diseases and control、Viral Infections and Outbreaks Research

ABSTRACT Viral infections disrupt glucose metabolism; however, their impact on disease prognosis in highly pathogenic viruses remains largely unknown. There is an additional need to investigate the antiviral mechanisms of glucose-lowering therapeutics. Here, our multicenter clinical study shows that hyperglycemia and pre-existing diabetes are independent risk factors for mortality in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging and highly pathogenic bunyavirus. SFTSV infection triggers gluconeogenesis, which, in turn, inhibits AMPK activity and subsequent interferon I (IFN-I) responses, thereby facilitating viral replication. In vitro and animal studies further reveal that metformin inhibits SFTSV replication by suppressing autophagy through the AMPK-mTOR pathway, contributing to protection against lethal SFTSV infection in mice. Importantly, our large cohort study demonstrates that metformin reduces viremia and SFTSV-related mortality in patients with hyperglycemia or pre-existing diabetes, contrasting with the disadvantageous effect of insulin. These findings highlight the promising therapeutic potential of metformin in treating viral infections, particularly among individuals with hyperglycemia or diabetes. IMPORTANCE Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne bunyavirus, causes severe hemorrhagic fever with a high mortality rate. Previous studies have shown metabolic disturbances, part...