ISDA: 8ZQ8

Deposition Date 2024-06-01

Release Date 2025-06-11

Last Version Date 2026-06-24

Entry Detail

PDB ID:

8ZQ8

Keywords:

VIRAL PROTEIN

Title:

SARS-Cov-2 3CL protease in complex with macrocyclic inhibitor CG-1039

Biological Source:

Source Organism(s):

Severe acute respiratory syndrome coronavirus 2 (Taxon ID: 2697049)

Expression System(s):

Escherichia coli bl21(de3)

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

1.77 Å

R-Value Free:

0.22

R-Value Work:

0.16

R-Value Observed:

0.16

Space Group:

C 1 2 1

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Macromolecular Entities

Structures with similar UniProt ID

Structural Superimposition Protein Blast

Polymer Type:polypeptide(L)
Molecule:3C-like proteinase nsp5
Gene (Uniprot):rep
Chain IDs:A
Chain Length:316
Number of Molecules:1
Biological Source:Severe acute respiratory syndrome coronavirus 2

UniProt ID:P0DTD1 Pfam ID:PF05409 EC:2.7.7.48

Ligand Molecules

A1D8T

Primary Citation

Discovery of macrocyclic covalent inhibitors for severe acute respiratory syndrome coronavirus 2 3CL protease.

Tang, X, Hou, K, Chen, X, Fan, W, Wu, H, Lu, C, He, G.X.Show

Bioorg.Med.Chem. 111 117846 117846 (2024)

PMID: 39106653 DOI: 10.1016/j.bmc.2024.117846

Abstact

The coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spread worldwide for more than 3 years. Although the hospitalization rate and mortality have decreased dramatically due to wide vaccination effort and improved treatment options, the disease is still a global health issue due to constant viral mutations, causing negative impact on social and economic activities. In addition, long COVID and complications arising from COVID-19 weeks after infection have become a concern for public health experts. Therefore, better treatments for COVID-19 are still needed. Herein, we describe a class of macrocyclic peptidomimetic compounds that are potent inhibitors of SARS-Cov-2 3CL protease (3CL(pro)). Significantly, some of the compounds showed a higher stability against human liver microsomes (HLM t(1/2) > 180 min) and may be suitable for oral administration without the need for a pharmacokinetic (PK) boosting agent such as ritonavir.

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Primary Citation of related structures

Abstact

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