Page Taylor M, Nie Chuanxiong, Neander Lenard, Povolotsky Tatyana L, Sahoo Anil Kumar, Nickl Philip, Adler Julia M, Bawadkji Obida, Radnik Jörg, Achazi Katharina, Ludwig Kai, Lauster Daniel, Netz Roland R, Trimpert Jakob, Kaufer Benedikt, Haag Rainer, Donskyi Ievgen S
Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
Physics Department, Freie Universität Berlin, Arnimallee 14, 14195, Berlin, Germany.
Small. 2023 Apr;19(15):e2206154. doi: 10.1002/smll.202206154. Epub 2023 Jan 18.
As virus outbreaks continue to pose a challenge, a nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading to virus inhibition. Similarly, hydrophobic C fullerene can prevent virus infection via interactions with hydrophobic cavities of surface proteins. Here, two strategies are combined to inhibit infection of SARS-CoV-2 variants in vitro. Effective inhibitory concentrations in the millimolar range highlight the significance of bare fullerene's hydrophobic moiety and electrostatic interactions of polysulfates with surface proteins of SARS-CoV-2. Furthermore, microscale thermophoresis measurements support that fullerene linear polyglycerol sulfates interact with the SARS-CoV-2 virus via its spike protein, and highlight importance of electrostatic interactions within it. All-atom molecular dynamics simulations reveal that the fullerene binding site is situated close to the receptor binding domain, within 4 nm of polyglycerol sulfate binding sites, feasibly allowing both portions of the material to interact simultaneously.
随着病毒爆发持续构成挑战，一种非特异性病毒抑制剂可带来显著益处，尤其是针对呼吸道病毒。聚甘油硫酸盐最近成为有前景的药物，它通过静电作用介导细胞与病毒之间的相互作用，从而抑制病毒。同样，疏水性的C富勒烯可通过与表面蛋白的疏水腔相互作用来预防病毒感染。在此，将两种策略结合起来在体外抑制SARS-CoV-2变体的感染。毫摩尔范围内的有效抑制浓度凸显了裸富勒烯疏水部分以及聚硫酸盐与SARS-CoV-2表面蛋白静电相互作用的重要性。此外，微量热泳测定结果支持富勒烯线性聚甘油硫酸盐通过其刺突蛋白与SARS-CoV-2病毒相互作用，并强调了其中静电相互作用的重要性。全原子分子动力学模拟表明，富勒烯结合位点位于靠近受体结合结构域的位置，在聚甘油硫酸盐结合位点的4纳米范围内，这使得该材料的两个部分有可能同时相互作用。
