Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China.
Carol Yu Centre for Infection, State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Viruses. 2022 Mar 6;14(3):549. doi: 10.3390/v14030549.
Our previous studies have shown that cholesterol-conjugated, peptide-based pan-coronavirus (CoV) fusion inhibitors can potently inhibit human CoV infection. However, only palmitic acid (C16)-based lipopeptide drugs have been tested clinically, suggesting that the development of C16-based lipopeptide drugs is feasible. Here, we designed and synthesized a C16-modified pan-CoV fusion inhibitor, EK1-C16, and found that it potently inhibited infection by SARS-CoV-2 and its variants of concern (VOCs), including Omicron, and other human CoVs and bat SARS-related CoVs (SARSr-CoVs). These results suggest that EK1-C16 could be further developed for clinical use to prevent and treat infection by the currently circulating MERS-CoV, SARS-CoV-2 and its VOCs, as well as any future emerging or re-emerging coronaviruses.
我们之前的研究表明，胆固醇缀合的基于肽的泛冠状病毒（CoV）融合抑制剂能够有效地抑制人类 CoV 感染。然而，仅对棕榈酸（C16）为基础的脂肽药物进行了临床测试，这表明 C16 为基础的脂肽药物的开发是可行的。在这里，我们设计并合成了一种 C16 修饰的泛 CoV 融合抑制剂 EK1-C16，并发现它能够有效地抑制 SARS-CoV-2 及其关注变种（VOCs），包括奥密克戎，以及其他人类 CoV 和蝙蝠 SARS 相关 CoV（SARSr-CoV）的感染。这些结果表明，EK1-C16 可以进一步开发用于临床，以预防和治疗目前流行的 MERS-CoV、SARS-CoV-2 及其 VOCs 以及任何未来新出现或重新出现的冠状病毒的感染。
