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潜在抑制剂可阻断 ACE2 与带有突变的 SARS-CoV-2 刺突蛋白结合。

Potential inhibitor for blocking binding between ACE2 and SARS-CoV-2 spike protein with mutations.

机构信息

Department of Otolaryngology, Chang Gung Memorial Hospital, Chiayi, Taiwan; Faculty of Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.

Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.

出版信息

Biomed Pharmacother. 2022 May;149:112802. doi: 10.1016/j.biopha.2022.112802. Epub 2022 Mar 9.

DOI:10.1016/j.biopha.2022.112802
PMID:35279013
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8906167/
Abstract

At the time of writing, more than 440 million confirmed coronavirus disease 2019 (COVID-19) cases and more than 5.97 million COVID-19 deaths worldwide have been reported by the World Health Organization since the start of the outbreak of the pandemic in Wuhan, China. During the COVID-19 pandemic, many variants of SARS-CoV-2 have arisen because of high mutation rates. N501Y, E484K, K417N, K417T, L452R and T478K in the receptor binding domain (RBD) region may increase the infectivity in several variants of SARS-CoV-2. In this study, we discovered that GB-1, developed from Chiehyuan herbal formula which obtained from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and RBD with Wuhan type, K417N-E484K-N501Y and L452R-T478K mutation. In addition, GB-1 inhibited the binding between ACE2 and RBD with a single mutation (E484K or N501Y), except the K417N mutation. In the compositions of GB-1, glycyrrhizic acid can inhibit the binding between ACE2 and RBD with Wuhan type, except K417N-E484K-N501Y mutation. Our results suggest that GB-1 could be a potential candidate for the prophylaxis of different variants of SARS-CoV-2 infection because of its inhibition of binding between ACE2 and RBD with different mutations (L452R-T478K, K417N-E484K-N501Y, N501Y or E484K).

摘要

截至撰写本文时,自中国武汉爆发大流行以来,世界卫生组织已报告全球超过 4.4 亿例 2019 年冠状病毒病(COVID-19)确诊病例和超过 597 万例 COVID-19 死亡病例。在 COVID-19 大流行期间,由于高突变率,SARS-CoV-2 的许多变体已经出现。受体结合域(RBD)区域中的 N501Y、E484K、K417N、K417T、L452R 和 T478K 可能会增加几种 SARS-CoV-2 变体的传染性。在这项研究中,我们发现,从嘉义朴子培天宫天上圣母获得的百草园草药配方开发的 GB-1 可以抑制武汉型、K417N-E484K-N501Y 和 L452R-T478K 突变的 ACE2 和 RBD 之间的结合。此外,GB-1 除 K417N 突变外,还抑制了 ACE2 和 RBD 之间具有单个突变(E484K 或 N501Y)的结合。在 GB-1 的成分中,甘草酸可以抑制武汉型 ACE2 和 RBD 之间的结合,除了 K417N-E484K-N501Y 突变。我们的结果表明,GB-1 可能是预防不同 SARS-CoV-2 变异感染的潜在候选药物,因为它可以抑制不同突变(L452R-T478K、K417N-E484K-N501Y、N501Y 或 E484K)的 ACE2 和 RBD 之间的结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/48d6821f0c18/gr10_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/f3d124b77fe6/ga1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/507a04917951/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/15c679c3d94a/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/e4b3063415e5/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/b376f9a55710/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/95a9032a9746/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/36f7c2c1ead4/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/7a1ecfc91641/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/c01dbddcb2d2/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/d2cb635e3795/gr9_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/48d6821f0c18/gr10_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/f3d124b77fe6/ga1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/507a04917951/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/15c679c3d94a/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/e4b3063415e5/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/b376f9a55710/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/95a9032a9746/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/36f7c2c1ead4/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/7a1ecfc91641/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/c01dbddcb2d2/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/d2cb635e3795/gr9_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c727/8906167/48d6821f0c18/gr10_lrg.jpg

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