Abstract：
The SARS-CoV-2 coronavirus is characterized by high mutation rates and significant infectivity, posing ongoing challenges for therapeutic intervention. To address potential challenges in the future, the continued development of effective drugs targeting SARS-CoV-2 remains an important task for the scientific as well as the pharmaceutical community. The main protease (Mpro) of SARS-CoV-2 is an ideal therapeutic target for COVID-19 drug development, leading to the introduction of various inhibitors, both covalent and non-covalent, each characterized by unique mechanisms of action and possessing inherent strengths and limitations. Natural products, being compounds naturally present in the environment, offer advantages such as low toxicity and diverse activities, presenting a viable source for antiviral drug development. Here, we identified a natural compound, rosmarinic acid, which exhibits significant inhibitory effects on the Mpro of the SARS-CoV-2. Through detailed structural biology analysis, we elucidated the precise crystal structure of the complex formed between rosmarinic acid and SARS-CoV-2 Mpro, revealing the molecular basis of its inhibitory mechanism. These findings not only enhance our understanding of the antiviral action of rosmarinic acid, but also provide valuable structural information and mechanistic insights for the further development of therapeutic strategies against SARS-CoV-2.
摘要：
SARS-CoV-2冠状病毒的特点是高突变率和显著的传染性,对治疗干预构成持续挑战。为了应对未来的潜在挑战，继续开发针对SARS-CoV-2的有效药物仍然是科学界和制药界的重要任务。SARS-CoV-2的主要蛋白酶（Mpro）是COVID-19药物开发的理想治疗靶标，导致各种抑制剂的引入，共价和非共价，每个特征都具有独特的作用机制，并具有固有的优势和局限性。天然产品,是环境中天然存在的化合物，具有低毒性和多种活性等优点，为抗病毒药物的开发提供了一个可行的来源。这里,我们发现了一种天然化合物,迷迭香酸,对SARS-CoV-2的Mpro表现出明显的抑制作用。通过详细的结构生物学分析,我们阐明了迷迭香酸与SARS-CoV-2Mpro之间形成的复合物的精确晶体结构，揭示其抑制机制的分子基础。这些发现不仅增强了我们对迷迭香酸抗病毒作用的理解，而且还为进一步开发针对SARS-CoV-2的治疗策略提供了有价值的结构信息和机制见解。
