Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), enters the host cells through two main pathways, both involving key interactions between viral envelope-anchored spike glycoprotein of the novel coronavirus and the host receptor, angiotensin-converting enzyme 2 (ACE2). To date, SARS-CoV-2 has infected up to 26 million people worldwide; yet, there is no clinically approved drug or vaccine available. Therefore, a rapid and coordinated effort to re-purpose clinically approved drugs that prevent or disrupt these critical entry pathways of SARS-CoV-2 spike glycoprotein interaction with human ACE2, could potentially accelerate the identification and clinical advancement of prophylactic and/or treatment options against COVID-19, thus providing possible countermeasures against viral entry, pathogenesis and survival. Herein, we discovered that Ambroxol hydrochloride (AMB), and its progenitor, Bromhexine hydrochloride (BHH), both clinically approved drugs are potent effective modulators of the key interaction between the receptor binding domain (RBD) of SARS-CoV-2 spike protein and human ACE2. We also found that both compounds inhibited SARS-CoV-2 infection-induced cytopathic effect at micromolar concentrations. Therefore, in addition to the known TMPRSS2 activity of BHH; we report for the first time that the BHH and AMB pharmacophore has the capacity to target and modulate yet another key protein-protein interaction essential for the two known SARS-CoV-2 entry pathways into host cells. Altogether, the potent efficacy, excellent safety and pharmacologic profile of both drugs along with their affordability and availability, makes them promising candidates for drug repurposing as possible prophylactic and/or treatment options against SARS-CoV-2 infection.

中文翻译：

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盐酸氨溴索抑制严重急性呼吸系统综合症冠状病毒2穗蛋白的受体结合域和重组人ACE2之间的相互作用。

严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）是冠状病毒病2019（COVID-19）的病原体，它通过两种主要途径进入宿主细胞，这两种途径均涉及新型病毒包膜锚定的刺突糖蛋白之间的关键相互作用。冠状病毒和宿主受体，血管紧张素转换酶2（ACE2）。迄今为止，SARS-CoV-2已感染全球2600万人。但是，尚无临床认可的药物或疫苗。因此，快速而协调地努力重新利用临床批准的药物来预防或破坏SARS-CoV-2穗糖蛋白与人ACE2相互作用的这些关键进入途径，可能会加速预防和/或治疗选择的鉴定和临床进展针对COVID-19，从而为病毒进入，发病机制和生存提供了可能的对策。本文中，我们发现盐酸氨溴索（AMB）及其祖先盐酸溴己辛（BHH）都是经过临床批准的药物，是SARS-CoV-2穗突蛋白的受体结合结构域（RBD）与蛋白之间的关键相互作用的有效有效调节剂。人类ACE2。我们还发现，这两种化合物在微摩尔浓度下均能抑制SARS-CoV-2感染引起的细胞病变作用。因此，除了已知的BHH的TMPRSS2活性外；我们首次报道BHH和AMB药效团具有靶向和调节另一个重要的蛋白质-蛋白质相互作用的能力，这是两个已知的SARS-CoV-2进入宿主细胞途径必不可少的。总而言之，强大的功效