Babulic Patrik, Cehlar Ondrej, Ondrovičová Gabriela, Moskalets Tetiana, Skrabana Rostislav, Leksa Vladimir
Laboratory of Molecular Immunology, Institute of Molecular Biology, Slovak Academy of Sciences, 845 51 Bratislava, Slovakia.
Department of Genetics, Faculty of Natural Sciences, Comenius University, 842 15 Bratislava, Slovakia.
Pharmaceuticals (Basel). 2024 Aug 4;17(8):1021. doi: 10.3390/ph17081021.
Since Coronavirus disease 2019 (COVID-19) still presents a considerable threat, it is beneficial to provide therapeutic supplements against it. In this respect, glycoprotein lactoferrin (LF) and lactoferricin (LFC), a natural bioactive peptide yielded upon digestion from the N-terminus of LF, are of utmost interest, since both have been shown to reduce infections of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for COVID-19, in particular via blockade of the virus priming and binding. Here, we, by means of biochemical and biophysical methods, reveal that LF directly binds to the S-protein of SARS-CoV-2. We determined thermodynamic and kinetic characteristics of the complex formation and mapped the mutual binding sites involved in this interaction, namely the N-terminal region of LF and the receptor-binding domain of the S-protein (RBD). These results may not only explain many of the observed protective effects of LF and LFC in SARS-CoV-2 infection but may also be instrumental in proposing potent and cost-effective supplemental tools in the management of COVID-19.
由于2019冠状病毒病（COVID-19）仍然构成相当大的威胁，提供针对它的治疗性补充剂是有益的。在这方面，糖蛋白乳铁蛋白（LF）和乳铁素（LFC）（一种从LF的N端消化产生的天然生物活性肽）备受关注，因为两者都已被证明可减少严重急性呼吸综合征冠状病毒2（SARS-CoV-2，即导致COVID-19的病毒）的感染，特别是通过阻断病毒引发和结合。在此，我们通过生化和生物物理方法揭示，LF直接与SARS-CoV-2的S蛋白结合。我们确定了复合物形成的热力学和动力学特征，并绘制了这种相互作用中涉及的相互结合位点，即LF的N端区域和S蛋白的受体结合域（RBD）。这些结果不仅可以解释LF和LFC在SARS-CoV-2感染中观察到的许多保护作用，还可能有助于提出在COVID-19管理中有效且经济高效的补充工具。
