Laboratory of Systems Biology, Institute of Experimental Plant Biology and Biotechnology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland.
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
Molecules. 2021 Apr 9;26(8):2157. doi: 10.3390/molecules26082157.
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a positive-strand RNA virus that causes severe respiratory syndrome in humans, which is now referred to as coronavirus disease 2019 (COVID-19). Since December 2019, the new pathogen has rapidly spread globally, with over 65 million cases reported to the beginning of December 2020, including over 1.5 million deaths. Unfortunately, currently, there is no specific and effective treatment for COVID-19. As SARS-CoV-2 relies on its spike proteins (S) to bind to a host cell-surface receptor angiotensin-converting enzyme-2(ACE2), and this interaction is proved to be responsible for entering a virus into host cells, it makes an ideal target for antiviral drug development. In this work, we design three very short peptides based on the ACE2 sequence/structure fragments, which may effectively bind to the receptor-binding domain (RBD) of S protein and may, in turn, disrupt the important virus-host protein-protein interactions, blocking early steps of SARS-CoV-2 infection. Two of our peptides bind to virus protein with affinity in nanomolar range, and as very short peptides have great potential for drug development.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是一种正链 RNA 病毒，可导致人类严重呼吸道综合征，现在称为 2019 年冠状病毒病（COVID-19）。自 2019 年 12 月以来，这种新病原体在全球迅速传播，截至 2020 年 12 月初，已报告超过 6500 万例病例，包括超过 150 万人死亡。不幸的是，目前尚无针对 COVID-19 的特效治疗方法。由于 SARS-CoV-2 依靠其刺突蛋白（S）与宿主细胞表面受体血管紧张素转换酶 2（ACE2）结合，并且该相互作用被证明是导致病毒进入宿主细胞的原因，因此它成为抗病毒药物开发的理想靶标。在这项工作中，我们根据 ACE2 序列/结构片段设计了三个非常短的肽，这些肽可能与 S 蛋白的受体结合域（RBD）有效结合，并可能反过来破坏重要的病毒-宿主蛋白-蛋白相互作用，从而阻断 SARS-CoV-2 感染的早期步骤。我们的两个肽与病毒蛋白的亲和力在纳摩尔范围内，由于短肽具有很大的药物开发潜力。
