Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome (SARS) caused by a virus known as SARS-Coronavirus 2 (SARS-CoV2). Without a targeted-medicine, this disease has been causing a massive humanitarian crisis not only in terms of mortality, but also imposing a lasting damage to social life and economic progress of humankind. Therefore, an immediate therapeutic strategy needs to be intervened to mitigate this global crisis. Here, we report a novel KepTide(TM) (Knock-End Peptide) therapy that nullifies SARS-CoV2 infection. SARS-CoV2 employs its surface glycoprotein spike (S-glycoprotein) to interact with angiotensin converting enzyme-2 (ACE-2) receptor for its infection in host cells. Based on our in-silico-based homology modeling study validated with a recent X-ray crystallographic structure (PDB ID:6M0J), we have identified that a conserved motif of S-glycoprotein that intimately engages multiple hydrogen-bond (H-bond) interactions with ACE-2 enzyme. Accordingly, we designed a peptide, termed as ACIS (ACE-2 Inhibitory motif of Spike), that displayed significant affinity towards ACE-2 enzyme as confirmed by biochemical assays such as BLItz and fluorescence polarization assays. Interestingly, more than one biochemical modifications were adopted in ACIS in order to enhance the inhibitory action of ACIS and hence called as KEpTide(TM). Consequently, a monolayer invasion assay, plaque assay and dual immunofluorescence analysis further revealed that KEpTide(TM) efficiently mitigated the infection of SARS-CoV2 in vitro in VERO E6 cells. Finally, evaluating the relative abundance of ACIS in lungs and the potential side-effects in vivo in mice, our current study discovers a novel KepTideTM therapy that is safe, stable, and robust to attenuate the infection of SARS-CoV2 virus if administered intranasally.

中文翻译：

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ACIS，一种新型KepTide™，与ACE-2受体结合并抑制灵长类肾脏细胞中SARS-CoV2病毒的感染：COVID-19的治疗意义

冠状病毒病2019（COVID-19）是由一种名为SARS冠状病毒2（SARS-CoV2）的病毒引起的严重急性呼吸系统综合症（SARS）。如果没有针对性药物，这种疾病不仅在死亡率上造成了巨大的人道主义危机，而且对人类的社会生活和经济发展造成了持久的损害。因此，需要介入立即的治疗策略以减轻这种全球危机。在这里，我们报告了一种新的KepTide™（敲除末端肽）疗法，该疗法可消除SARS-CoV2感染。SARS-CoV2利用其表面糖蛋白突触（S-糖蛋白）与血管紧张素转换酶2（ACE-2）受体相互作用，以感染宿主细胞。基于我们基于计算机内的同源性建模研究，该研究已通过最新的X射线晶体学结构（PDB ID：6M0J）进行了验证，我们已经发现，S-糖蛋白的保守基序与ACE-2酶紧密地参与了多个氢键（H键）相互作用。因此，我们设计了一种肽，称为ACIS（Spike的ACE-2抑制性基序），该肽对ACE-2酶表现出显着的亲和力，这已通过生物化学分析（例如BLItz和荧光偏振分析）证实。有趣的是，为了增强ACIS的抑制作用，在ACIS中采用了一种以上的生化修饰，因此被称为KEpTide TM。因此，单层侵袭测定，噬菌斑测定和双重免疫荧光分析进一步揭示了KEpTide TM有效地减轻了体外VERO E6细胞中SARS-CoV2的感染。最后，评估了肺中ACIS的相对丰度以及小鼠体内的潜在副作用，