Discovery of New Fusion Inhibitor Peptides against SARS-CoV-2 by Targeting the Spike S2 Subunit.
Discovery of New Fusion Inhibitor Peptides against SARS-CoV-2 by Targeting the Spike S2 Subunit.
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DOI：
10.4062/biomolther.2020.201
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发表时间：
2021-05-01
影响因子：
3.7
通讯作者：
Alkattan A
中科院分区：
文献类型：
--
作者：
Kandeel M;Yamamoto M;Tani H;Kobayashi A;Gohda J;Kawaguchi Y;Park BK;Kwon HJ;Inoue JI;Alkattan A
一种新的冠状病毒--严重急性呼吸综合征冠状病毒-2(SARS-CoV-2)在世界范围内引起了大流行。本研究的目的是开发新的抗SARS-CoV-2融合抑制剂，为开发新型抗病毒药物奠定基础。利用SARS-CoV-2尖峰蛋白(S)的七肽重复序列(Hr1和Hr2)的融合核心进行设计。总共产生了12个肽，包括一个短的或截短的24-聚体(肽#1)、一个长的36-聚体(肽#2)和10个肽#2的类似物。与SARS-CoV相比，SARS-CoV-2 S介导的细胞-细胞融合不能被最小长度的24肽所抑制。多肽2在1µM浓度下对S介导的细胞-细胞融合有较强的抑制作用。三个肽#2类似物的IC50值在低微摩尔范围内(4.7-9.8微克分子)。多肽2对SARS-CoV-2假病毒的IC50=1.49µM有抑制作用，具有较强的抑制病毒活性和安全性且无细胞毒性，为开发新的SARS-CoV-2预防和治疗药物提供了一条诱人的途径。
A novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), caused a worldwide pandemic. Our aim in this study is to produce new fusion inhibitors against SARS-CoV-2, which can be the basis for developing new antiviral drugs. The fusion core comprising the heptad repeat domains (HR1 and HR2) of SARS-CoV-2 spike (S) were used to design the peptides. A total of twelve peptides were generated, comprising a short or truncated 24-mer (peptide #1), a long 36-mer peptide (peptide #2), and ten peptide #2 analogs. In contrast to SARS-CoV, SARS-CoV-2 S-mediated cell-cell fusion cannot be inhibited with a minimal length, 24-mer peptide. Peptide #2 demonstrated potent inhibition of SARS-CoV-2 S-mediated cell-cell fusion at 1 µM concentration. Three peptide #2 analogs showed IC50 values in the low micromolar range (4.7-9.8 µM). Peptide #2 inhibited the SARS-CoV-2 pseudovirus assay at IC50=1.49 µM. Given their potent inhibition of viral activity and safety and lack of cytotoxicity, these peptides provide an attractive avenue for the development of new prophylactic and therapeutic agents against SARS-CoV-2.