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TitleA broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 120, Issue 26, Page e2303292120, Year 2023
Publish dateJun 27, 2023
AuthorsVito Thijssen / Daniel L Hurdiss / Oliver J Debski-Antoniak / Matthew A Spence / Charlotte Franck / Alexander Norman / Anupriya Aggarwal / Nadia J Mokiem / David A A van Dongen / Stein W Vermeir / Minglong Liu / Wentao Li / Marianthi Chatziandreou / Tim Donselaar / Wenjuan Du / Ieva Drulyte / Berend-Jan Bosch / Joost Snijder / Stuart G Turville / Richard J Payne / Colin J Jackson / Frank J M van Kuppeveld / Seino A K Jongkees /
PubMed AbstractThe 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- ...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.
External linksProc Natl Acad Sci U S A / PubMed:37339194 / PubMed Central
MethodsEM (single particle)
Resolution3.2 Å
Structure data

16144

8bon

EMDB-16144, PDB-8bon:
Structure of the SARS-CoV-2 spike glycoprotein in complex with the macrocyclic peptide S1B3inL1
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • synthetic construct (others)
  • tequatrovirus t4
KeywordsVIRAL PROTEIN / Glycoprotein / macrocyclic peptide / Complex / Inhibitor

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