Liu Ching-Hsuan, Kuo Yu-Ting, Lin Chien-Ju, Yen Feng-Lin, Wu Shu-Jing, Lin Liang-Tzung
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Department of Diagnostic Imaging, Chi Mei Medical Center, Tainan 710, Taiwan.
Viruses. 2025 Aug 5;17(8):1086. doi: 10.3390/v17081086.
The emergence of SARS-CoV-2 variants highlights the urgent need for novel therapeutic strategies, particularly entry inhibitors that could efficiently prevent viral infection. Medicinal herbs and herbal combination formulas have long been recognized for their effects in treating infectious diseases and their antiviral properties, thus providing abundant resources for the discovery of antiviral candidates. While many candidates have been suggested to have antiviral activity against SARS-CoV-2 infection, few have been validated for their mechanisms, including possible effects on viral entry. This study aimed to identify SARS-CoV-2 entry inhibitors from medicinal herbs and herbal formulas that are known for heat-clearing and detoxifying properties and/or antiviral activities. A SARS-CoV-2 pseudoparticle (SARS-CoV-2pp) system was used to assess mechanism-specific entry inhibition. Our results showed that the methanol extract of rhizome, as well as the water extracts of rhizome, Xiao Chai Hu Tang (XCHT), and Sheng Ma Ge Gen Tang (SMGGT), have substantial inhibitory effects on the entry of SARS-CoV-2pps into host cells. Given the observation that exhibited the most potent inhibition and is a constituent of SMGGT, we further investigated the major compounds of the herb and identified caffeic acid as a bioactive component for blocking SARS-CoV-2pp entry. Entry inhibition of and caffeic acid was validated on both wild-type and the currently dominant JN.1 strain SARS-CoV-2pp systems. Moreover, caffeic acid was able to both inactivate the pseudoparticles and prevent their entry into pretreated host cells. The results support the traditional use of these herbal medicines and underscore their potential as valuable resources for identifying active compounds and developing therapeutic entry inhibitors for the management of COVID-19.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的出现凸显了对新型治疗策略的迫切需求，尤其是能够有效预防病毒感染的进入抑制剂。草药和草药复方长期以来因其在治疗传染病方面的作用及其抗病毒特性而受到认可，从而为发现抗病毒候选药物提供了丰富的资源。虽然许多候选药物被认为具有抗SARS-CoV-2感染的抗病毒活性，但很少有药物的作用机制得到验证，包括对病毒进入的可能影响。本研究旨在从以清热、解毒特性和/或抗病毒活性而闻名的草药和草药配方中鉴定SARS-CoV-2进入抑制剂。使用SARS-CoV-2假病毒颗粒（SARS-CoV-2pp）系统评估特定机制的进入抑制作用。我们的结果表明，[具体植物根茎]的甲醇提取物以及[具体植物根茎]、小柴胡汤（XCHT）和升麻葛根汤（SMGGT）的水提取物对SARS-CoV-2pp进入宿主细胞具有显著的抑制作用。鉴于观察到[具体植物根茎]表现出最有效的抑制作用且是SMGGT的一种成分，我们进一步研究了该草药的主要化合物，并确定咖啡酸是阻断SARS-CoV-2pp进入的生物活性成分。在野生型和当前占主导地位的JN.1株SARS-CoV-2pp系统上均验证了[具体植物根茎]和咖啡酸的进入抑制作用。此外，咖啡酸能够使假病毒颗粒失活并阻止其进入预处理的宿主细胞。这些结果支持了这些草药的传统用途，并强调了它们作为识别活性化合物和开发用于管理COVID-19的治疗性进入抑制剂的宝贵资源的潜力。
