CRI Center for Chemical Proteomics, Department of Chemistry, Seoul National University, Seoul, 08826, Korea.
Department of Chemical Engineering & Biotechnology, Korea Polytechnic University, Siheung, 15073, Korea.
Angew Chem Int Ed Engl. 2022 Mar 7;61(11):e202115695. doi: 10.1002/anie.202115695. Epub 2022 Feb 1.
The emergence of SARS-CoV-2 variants is a significant concern in developing effective therapeutics and vaccines in the middle of the ongoing COVID-19 pandemic. Here, we have identified a novel small molecule that inhibited the interactions between SARS-CoV-2 spike RBDs and ACE2 by modulating ACE2 without impairing its enzymatic activity necessary for normal physiological functions. Furthermore, the identified compounds suppressed viral infection in cultured cells by inhibiting the entry of ancestral and variant SARS-CoV-2. Our study suggests that targeting ACE2 could be a novel therapeutic strategy to inhibit SARS-CoV-2 entry into host cells and prevent the development of COVID-19.
在当前 COVID-19 大流行期间，SARS-CoV-2 变体的出现是开发有效治疗方法和疫苗的重大关注点。在这里，我们发现了一种新型小分子，它通过调节 ACE2 而不损害其正常生理功能所需的酶活性，来抑制 SARS-CoV-2 刺突 RBD 与 ACE2 之间的相互作用。此外，所鉴定的化合物通过抑制原始和变体 SARS-CoV-2 的进入来抑制培养细胞中的病毒感染。我们的研究表明，靶向 ACE2 可能是一种抑制 SARS-CoV-2 进入宿主细胞并预防 COVID-19 发展的新型治疗策略。
