Department of Biochemistry, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
Center of Life Nano and Neuro Science, Institute of Italian Technology, Viale Regina Elena 291, 00181 Rome, Italy.
Int J Mol Sci. 2022 May 13;23(10):5436. doi: 10.3390/ijms23105436.
The present investigation focuses on the analysis of the interactions among human lactoferrin (LF), SARS-CoV-2 receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2) receptor in order to assess possible mutual interactions that could provide a molecular basis of the reported preventative effect of lactoferrin against CoV-2 infection. In particular, kinetic and thermodynamic parameters for the pairwise interactions among the three proteins were measured via two independent techniques, biolayer interferometry and latex nanoparticle-enhanced turbidimetry. The results obtained clearly indicate that LF is able to bind the ACE2 receptor ectodomain with significantly high affinity, whereas no binding to the RBD was observed up to the maximum "physiological" lactoferrin concentration range. Lactoferrin, above 1 µM concentration, thus appears to directly interfere with RBD-ACE2 binding, bringing about a measurable, up to 300-fold increase of the K value relative to RBD-ACE2 complex formation.
本研究集中分析人乳铁蛋白（LF）、SARS-CoV-2 受体结合域（RBD）和人血管紧张素转换酶 2（ACE2）受体之间的相互作用，以评估可能存在的相互作用，为乳铁蛋白对 CoV-2 感染的预防作用提供分子基础。
特别是，通过两种独立的技术——生物层干涉测量法和乳胶纳米颗粒增强比浊法，测量了这三种蛋白质之间的成对相互作用的动力学和热力学参数。
研究结果清楚地表明，LF 能够与 ACE2 受体胞外域以高亲和力结合，而在最大“生理”乳铁蛋白浓度范围内未观察到与 RBD 的结合。
因此，乳铁蛋白在 1 µM 以上浓度时，似乎直接干扰 RBD-ACE2 结合，导致 K 值相对于 RBD-ACE2 复合物形成增加了可测量的 300 倍。
