Coghi Paolo, Yun Xiao Yun, Ng Jerome P L, Law Betty Yuan Kwan, Memo Maurizio, Gianoncelli Alessandra, Wong Vincent Kam Wai, Ribaudo Giovanni
School of Pharmacy, Macau University of Science and Technology, Taipa, Macau, China.
Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China.
Nat Prod Res. 2022 Dec;36(23):6150-6155. doi: 10.1080/14786419.2022.2057492. Epub 2022 Mar 25.
The interaction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) of spike protein with angiotensin-converting enzyme 2 (ACE2) mediates cell invasion. While this interaction mechanism is conserved, the RBD is affected by amino acid mutations in variants such as Delta and Omicron, resulting in enhanced transmissibility and altered ligand binding. Tanshinones are currently investigated as multi-target antiviral agents, but the studies were limited to the original SARS-CoV-2. This study aims at investigating the interaction of tanshinones with the Delta RBD. Chloroquine, methylene blue and pyronaridine, antimalarials previously identified as SARS-CoV-2 RBD binders, were studied for reference. Docking indicated the best scores for tanshinones, while bio-layer interferometry and molecular dynamics highlighted methylene blue as the best Delta RBD binder, although with decreased affinity with respect to the original strain.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白的受体结合域（RBD）与血管紧张素转换酶2（ACE2）的相互作用介导细胞侵袭。虽然这种相互作用机制是保守的，但RBD会受到Delta和Omicron等变体中氨基酸突变的影响，导致传播性增强和配体结合改变。丹参酮目前作为多靶点抗病毒药物进行研究，但研究仅限于原始的SARS-CoV-2。本研究旨在研究丹参酮与Delta RBD的相互作用。作为先前鉴定的SARS-CoV-2 RBD结合剂的抗疟药氯喹、亚甲蓝和咯萘啶用作参考研究。对接显示丹参酮得分最高，而生物层干涉术和分子动力学突出显示亚甲蓝是最佳的Delta RBD结合剂，尽管相对于原始毒株其亲和力有所降低。
