Lysine-selective molecular tweezers (MTs) are supramolecular host molecules displaying a remarkably broad spectrum of biologic activities. MTs act as inhibitors of the self-assembly and toxicity of amyloidogenic proteins using a unique mechanism. They destroy viral membranes and inhibit infection by enveloped viruses, such as HIV-1 and SARS-CoV-2, by mechanisms unrelated to their action on protein self-assembly. They also disrupt biofilm of Gram-positive bacteria. The efficacy and safety of MTs have been demonstrated in vitro, in cell culture, and in vivo, suggesting that these versatile compounds are attractive therapeutic candidates for various diseases, infections, and injuries. A lead compound called CLR01 has been shown to inhibit the aggregation of various amyloidogenic proteins, facilitate their clearance in vivo, prevent infection by multiple viruses, display potent anti-biofilm activity, and have a high safety margin in animal models. The inhibitory effect of CLR01 against amyloidogenic proteins is highly specific to abnormal self-assembly of amyloidogenic proteins with no disruption of normal mammalian biologic processes at the doses needed for inhibition. Therapeutic effects of CLR01 have been demonstrated in animal models of proteinopathies, lysosomal-storage diseases, and spinal-cord injury. Here we review the activity and mechanisms of action of these intriguing compounds and discuss future research directions.

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分子镊子：具有广谱生物应用的超分子宿主

赖氨酸选择性分子镊子（MT）是超分子宿主分子，具有非常广泛的生物活性。MT 通过独特的机制充当淀粉样蛋白自组装和毒性的抑制剂。它们通过与蛋白质自组装作用无关的机制破坏病毒膜并抑制 HIV-1 和 SARS-CoV-2 等包膜病毒的感染。它们还会破坏革兰氏阳性细菌的生物膜。MT 的功效和安全性已在体外、细胞培养和体内得到证明，表明这些多功能化合物是治疗各种疾病、感染和损伤的有吸引力的候选药物。一种名为 CLR01 的先导化合物已被证明可以抑制各种淀粉样蛋白的聚集，促进它们在体内的清除，预防多种病毒感染，表现出有效的抗生物膜活性，并且在动物模型中具有较高的安全裕度。CLR01 对淀粉样蛋白的抑制作用对淀粉样蛋白的异常自组装具有高度特异性，在抑制所需的剂量下不会破坏正常哺乳动物的生物过程。CLR01 的治疗作用已在蛋白质病、溶酶体贮积病和脊髓损伤的动物模型中得到证实。在这里，我们回顾这些有趣化合物的活性和作用机制，并讨论未来的研究方向。CLR01 对淀粉样蛋白的抑制作用对淀粉样蛋白的异常自组装具有高度特异性，在抑制所需的剂量下不会破坏正常哺乳动物的生物过程。CLR01 的治疗作用已在蛋白质病、溶酶体贮积病和脊髓损伤的动物模型中得到证实。在这里，我们回顾这些有趣化合物的活性和作用机制，并讨论未来的研究方向。CLR01 对淀粉样蛋白的抑制作用对淀粉样蛋白的异常自组装具有高度特异性，在抑制所需的剂量下不会破坏正常哺乳动物的生物过程。CLR01 的治疗作用已在蛋白质病、溶酶体贮积病和脊髓损伤的动物模型中得到证实。在这里，我们回顾这些有趣化合物的活性和作用机制，并讨论未来的研究方向。