ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Prog Mol Subcell Biol. 2022;61:145-189. doi: 10.1007/978-3-031-01237-2_7.
Polyanions as polymers carrying multiple negative charges have been extensively studied with regard to their potential antiviral activity. Most studies to date focused on organic polyanionic polymers, both natural and synthetic. The inorganic polymer, polyphosphate (polyP), despite the ubiquitous presence of this molecule from bacteria to man, has attracted much less attention. More recently, and accelerated by the search for potential antiviral agents in the fight against the pandemic caused by the coronavirus SARS-CoV-2, it turned out that polyP disrupts the first step of the viral replication cycle, the interaction of the proteins in the virus envelope and in the cell membrane that are involved in the docking process of the virus with the target host cell. Experiments on a molecular level using the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the cellular angiotensin converting enzyme 2 (ACE2) receptor revealed that polyP strongly inhibits the binding reaction through an electrostatic interaction between the negatively charged centers of the polyP molecule and a cationic groove, which is formed by positively charged amino acids on the RBD surface. In addition, it was found that polyP, due to its morphogenetic and energy delivering activities, enhances the antiviral host innate immunity defense of the respiratory epithelium. The underlying mechanisms and envisaged application of polyP in the therapy and prevention of COVID-19 are discussed.
多阴离子作为带有多个负电荷的聚合物，其潜在的抗病毒活性已得到广泛研究。迄今为止，大多数研究都集中在有机多阴离子聚合物，包括天然和合成聚合物。无机聚合物多磷酸盐（polyP），尽管这种分子在从细菌到人等各种生物中普遍存在，但却引起的关注要少得多。最近，由于人们在对抗由冠状病毒 SARS-CoV-2 引起的大流行的过程中寻找潜在的抗病毒药物，人们发现 polyP 破坏了病毒复制周期的第一步，即病毒包膜中的蛋白质与参与病毒与靶宿主细胞对接过程的细胞膜中的蛋白质之间的相互作用。使用 SARS-CoV-2 刺突蛋白的受体结合域（RBD）和细胞血管紧张素转换酶 2（ACE2）受体在分子水平上进行的实验表明，polyP 通过 polyP 分子的带负电荷中心与 RBD 表面上带正电荷的氨基酸形成的阳离子槽之间的静电相互作用强烈抑制结合反应。此外，还发现 polyP 由于其形态发生和能量传递活性，增强了呼吸道上皮细胞的抗病毒固有免疫防御。讨论了 polyP 在 COVID-19 治疗和预防中的作用机制和预期应用。
