Institute of Molecular and Cellular Biology, University Miguel Hernández, E-03206 Elche (Alicante), Spain.
J Phys Chem B. 2010 Jul 1;114(25):8544-54. doi: 10.1021/jp102619w.
Arbidol, a broad and potent antiviral molecule, incorporates rapidly into membranes. To gain further insight into the mode of action of Arbidol, since the exact antiviral mechanism of Arbidol is unknown, I examined its interaction and effects on model membranes composed of saturated phospholipids by performing a detailed biophysical study using calorimetry and infrared spectroscopy. Arbidol interacts and modifies the physicochemical properties of the phospholipids in the membrane, having a significant effect on negatively charged phospholipids but a minor one on zwitterionic phospholipids. The data suggest that Arbidol is located at the interface of the membrane, participates in hydrogen bonding either with water or the phospholipid or both, and decreases the hydrogen bonding network of the phospholipids giving place to a phospholipid phase similar to the dehydrated solid one. The significant effects produced on negatively charged phospholipids suggest that the active molecule of Arbidol in the membrane is the protonated one, that is, the positively charged molecule. These data suggest that the potent antiviral effects of Arbidol are mediated at least in part through its membranotropic effects, likely giving place to the formation of perturbed membrane structures. These modifications interfere with proper membrane functioning and should be responsible for its broad antiviral activity.
阿比多尔是一种广谱强效的抗病毒分子，能迅速融入细胞膜。为了更深入地了解阿比多尔的作用机制，由于其确切的抗病毒机制尚不清楚，我通过使用量热法和红外光谱对由饱和磷脂组成的模型膜进行详细的生物物理研究，来检查阿比多尔与模型膜的相互作用及其对模型膜的影响。阿比多尔与膜中的磷脂相互作用并改变其理化性质，对带负电荷的磷脂有显著影响，但对带正电荷的磷脂影响较小。数据表明，阿比多尔位于膜的界面处，参与氢键的形成，与水或磷脂或两者都相互作用，并降低磷脂的氢键网络，形成类似于脱水固体的磷脂相。对带负电荷的磷脂产生的显著影响表明，阿比多尔在膜中的活性分子是质子化的，即带正电荷的分子。这些数据表明，阿比多尔的强效抗病毒作用至少部分是通过其跨膜作用介导的，可能导致膜结构的扰动形成。这些修饰干扰了膜的正常功能，应该是其广谱抗病毒活性的原因。
