25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses.
25-Hydroxycholesterol-Conjugated EK1 Peptide with Potent and Broad-Spectrum Inhibitory Activity against SARS-CoV-2, Its Variants of Concern, and Other Human Coronaviruses.
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DOI：
10.3390/ijms222111869
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发表时间：
2021-11-01
影响因子：
5.6
通讯作者：
Jiang S
中科院分区：
文献类型：
--
作者：
Lan Q;Wang C;Zhou J;Wang L;Jiao F;Zhang Y;Cai Y;Lu L;Xia S;Jiang S
由SARS-CoV-2感染引起的COVID-19大流行对全球公共卫生和经济构成严重威胁。据报道，胆固醇25-羟化酶（CH25H）的酶产物25-羟基胆固醇（25-HC）具有有效的抗sars - cov -2活性。在这里，我们发现25-HC与泛冠状病毒（CoV）融合抑制剂EK1肽结合，显示出协同抗病毒活性。随后，我们利用25-HC修饰的方法设计并合成了一系列25-HC修饰的肽，发现25-HC修饰的EK1肽（EK1P4HC）对SARS-CoV-2、其关注变体（VOCs）和其他人类cov，如HCoV-OC43和HCoV-229E引起的感染非常有效。EK1P4HC可以保护新生小鼠免受致命的HCoV-OC43感染，这表明25-HC与基于肽的病毒抑制剂结合是提高其抗病毒活性的可行且普遍的策略。
The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity.
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DOI：
10.1056/nejmoa2029849
发表时间：
2021-01-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
影响因子：
39.3
作者：
Zhou W;Wang W
通讯作者：
Wang W
影响因子：
64.5
作者：
Hoffmann M;Arora P;Groß R;Seidel A;Hörnich BF;Hahn AS;Krüger N;Graichen L;Hofmann-Winkler H;Kempf A;Winkler MS;Schulz S;Jäck HM;Jahrsdörfer B;Schrezenmeier H;Müller M;Kleger A;Münch J;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
7.3
作者：
Wang C;Zhao L;Xia S;Zhang T;Cao R;Liang G;Li Y;Meng G;Wang W;Shi W;Zhong W;Jiang S;Liu K
通讯作者：
Liu K
影响因子：
15.1
作者：
Gunst JD;Staerke NB;Pahus MH;Kristensen LH;Bodilsen J;Lohse N;Dalgaard LS;Brønnum D;Fröbert O;Hønge B;Johansen IS;Monrad I;Erikstrup C;Rosendal R;Vilstrup E;Mariager T;Bove DG;Offersen R;Shakar S;Cajander S;Jørgensen NP;Sritharan SS;Breining P;Jespersen S;Mortensen KL;Jensen ML;Kolte L;Frattari GS;Larsen CS;Storgaard M;Nielsen LP;Tolstrup M;Sædder EA;Østergaard LJ;Ngo HTT;Jensen MH;Højen JF;Kjolby M;Søgaard OS
通讯作者：
Søgaard OS