[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleIn Silico Discovery of Small Molecule Modulators Targeting the Achilles' Heel of SARS-CoV-2 Spike Protein.
Journal, issue, pagesACS Cent Sci, Vol. 9, Issue 2, Page 252-265, Year 2023
Publish dateFeb 22, 2023
AuthorsQing Wang / Fanhao Meng / Yuting Xie / Wei Wang / Yumin Meng / Linjie Li / Tao Liu / Jianxun Qi / Xiaodan Ni / Sanduo Zheng / Jianhui Huang / Niu Huang /
PubMed AbstractThe spike protein of SARS-CoV-2 has been a promising target for developing vaccines and therapeutics due to its crucial role in the viral entry process. Previously reported cryogenic electron ...The spike protein of SARS-CoV-2 has been a promising target for developing vaccines and therapeutics due to its crucial role in the viral entry process. Previously reported cryogenic electron microscopy (cryo-EM) structures have revealed that free fatty acids (FFA) bind with SARS-CoV-2 spike protein, stabilizing its closed conformation and reducing its interaction with the host cell target in vitro. Inspired by these, we utilized a structure-based virtual screening approach against the conserved FFA-binding pocket to identify small molecule modulators of SARS-CoV-2 spike protein, which helped us identify six hits with micromolar binding affinities. Further evaluation of their commercially available and synthesized analogs enabled us to discover a series of compounds with better binding affinities and solubilities. Notably, our identified compounds exhibited similar binding affinities against the spike proteins of the prototypic SARS-CoV-2 and a currently circulating Omicron BA.4 variant. Furthermore, the cryo-EM structure of the compound SPC-14 bound spike revealed that SPC-14 could shift the conformational equilibrium of the spike protein toward the closed conformation, which is human ACE2 (hACE2) inaccessible. Our identified small molecule modulators targeting the conserved FFA-binding pocket could serve as the starting point for the future development of broad-spectrum COVID-19 intervention treatments.
External linksACS Cent Sci / PubMed:36844485 / PubMed Central
MethodsEM (single particle)
Resolution3.06 - 3.27 Å
Structure data

34464

8h3d

EMDB-34464, PDB-8h3d:
Structure of apo SARS-CoV-2 spike protein with one RBD up
Method: EM (single particle) / Resolution: 3.27 Å

34465

8h3e

EMDB-34465, PDB-8h3e:
Complex structure of a small molecule (SPC-14) bound SARS-CoV-2 spike protein, closed state
Method: EM (single particle) / Resolution: 3.06 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-Q83:
7-(6-nitro-2,3-dihydroindol-1-yl)-7-oxidanylidene-heptanoic acid

Source
  • severe acute respiratory syndrome coronavirus 2
  • tequatrovirus t4
KeywordsVIRAL PROTEIN / SARS-CoV-2 / spike protein / apo / complex / small molecule / closed

+
About Yorodumi Papers

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more