Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Sungnam-daero, Sujung-gu, Seongnam-si 461-701, Republic of Korea.
Int J Mol Sci. 2023 Apr 1;24(7):6583. doi: 10.3390/ijms24076583.
As emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (Omicron) continue to outpace and negate combinatorial vaccines and monoclonal antibody therapies targeting the spike protein (S) receptor binding domain (RBD), the appetite for developing similar COVID-19 treatments has significantly diminished, with the attention of the scientific community switching to long COVID treatments. However, treatments that reduce the risk of "post-COVID-19 syndrome" and associated sequelae remain in their infancy, particularly as no established criteria for diagnosis currently exist. Thus, alternative therapies that reduce infection and prevent the broad range of symptoms associated with 'post-COVID-19 syndrome' require investigation. This review begins with an overview of the parasitic-diarylamidine connection, followed by the renin-angiotensin system (RAS) and associated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSSR2) involved in SARS-CoV-2 infection. Subsequently, the ability of diarylamidines to inhibit S-protein binding and various membrane serine proteases associated with SARS-CoV-2 and parasitic infections are discussed. Finally, the roles of diarylamidines (primarily DIZE) in vaccine efficacy, epigenetics, and the potential amelioration of long COVID sequelae are highlighted.
随着新兴的严重急性呼吸系统综合征冠状病毒 2 型（SARS-CoV-2）变体（奥密克戎）不断超越并否定针对刺突蛋白（S）受体结合域（RBD）的组合疫苗和单克隆抗体疗法，开发类似 COVID-19 治疗方法的兴趣显著降低，科学界的注意力转向了长期 COVID 的治疗方法。然而，降低“新冠后综合征”风险和相关后遗症的治疗方法仍处于起步阶段，特别是因为目前尚无明确的诊断标准。因此，需要研究能够降低感染风险并预防与“新冠后综合征”相关的广泛症状的替代疗法。本综述首先概述了寄生虫-二芳基脒的联系，然后介绍了肾素-血管紧张素系统（RAS）以及涉及 SARS-CoV-2 感染的相关血管紧张素转换酶 2（ACE2）和跨膜丝氨酸蛋白酶 2（TMPRSS2）。随后，讨论了二芳基脒抑制 S 蛋白结合以及与 SARS-CoV-2 和寄生虫感染相关的各种膜丝氨酸蛋白酶的能力。最后，强调了二芳基脒（主要是 DIZE）在疫苗功效、表观遗传学以及长期 COVID 后遗症的潜在改善方面的作用。
