A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein

被引：13

作者：

Thijssen, Vito ^{[1
,2
]}

Hurdiss, Daniel L. ^{[3
]}

Debski-Antoniak, Oliver J. ^{[3
]}

Spence, Matthew A. ^{[4
]}

Franck, Charlotte ^{[5
,6
]}

Norman, Alexander ^{[5
,6
]}

Aggarwal, Anupriya ^{[7
]}

Mokiem, Nadia J. ^{[8
,9
]}

van Dongen, David A. A. ^{[1
,8
,9
]}

Vermeir, Stein W. ^{[1
,2
]}

Liu, Minglong ^{[1
,2
]}

Li, Wentao ^{[3
]}

Chatziandreou, Marianthi ^{[3
]}

Donselaar, Tim ^{[3
]}

Du, Wenjuan ^{[3
]}

Drulyte, Ieva ^{[10
]}

Bosch, Berend-Jan ^{[3
]}

Snijder, Joost ^{[8
,9
]}

Turville, Stuart G. ^{[7
]}

Payne, Richard J. ^{[5
,6
]}

Jackson, Colin J. ^{[4
,11
,12
]}

van Kuppeveld, Frank J. M. ^{[3
]}

Jongkees, Seino A. K. ^{[1
,2
]}

机构：

[1] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Chem Biol & Drug Discovery, NL-3584 CG Utrecht, Netherlands

[2] Vrije Univ Amsterdam, Amsterdam Inst Mol & Life Sci, Chem & Pharmaceut Sci, NL-1081 HV Amsterdam, Netherlands

[3] Univ Utrecht, Fac Vet Med, Dept Biomol Hlth Sci, Sect Virol,Div Infect Dis & Immunol, NL-3584 CL Utrecht, Netherlands

[4] Australian Natl Univ, Res Sch Chem, Canberra, ACT 2601, Australia

[5] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia

[6] Univ Sydney, Australian Res Council, Ctr Excellence Innovat Peptide & Prot Sci, Sydney, NSW 2006, Australia

[7] Kirby Inst, Sydney, NSW 2052, Australia

[8] Univ Utrecht, Bijvoet Ctr Biomol Res, Biomol Mass Spectrometry & Prote, NL-3584 CH Utrecht, Netherlands

[9] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CH Utrecht, Netherlands

[10] Thermo Fisher Sci, Mat & Struct Anal, NL-5651 GG Eindhoven, Netherlands

[11] Australian Natl Univ, Australian Res Council, Ctr Excellence Innovat Peptide & Prot Sci, Canberra, ACT 2601, Australia

[12] Australian Natl Univ, Australian Res Council, Ctr Excellence Synthet Biol, Canberra, ACT 2601, Australia

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2023年 / 120卷 / 26期

基金：

澳大利亚研究理事会; 荷兰研究理事会; 比尔及梅琳达.盖茨基金会;

关键词：

macrocyclic peptides; mRNA display; SARS-CoV-2; antivirals; Cryo-EM; DISCOVERY; APTAMERS; DOMAIN;

D O I：

10.1073/pnas.2303292120

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed to safeguard against emerging variants and future pandemics. We used messenger RNA (mRNA) display under a reprogrammed genetic code to find a spike-targeting macrocyclic peptide that inhibits SARS-CoV- 2 (severe acute respiratory syndrome coronavirus 2) Wuhan strain infection and pseudoviruses containing spike proteins of SARS-CoV- 2 variants or related sarbecoviruses. Structural and bioinformatic analyses reveal a conserved binding pocket between the receptor-binding domain, N-terminal domain, and S2 region, distal to the angiotensin-converting enzyme 2 receptor-interaction site. Our data reveal a hitherto unexplored site of vulnerability in sarbecoviruses that peptides and potentially other drug-like molecules can target.

引用

页数：7

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