Related Experiment Video
Updated: Sep 12, 2025
08:40
Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting
Published on: March 1, 2019
59.2K
Structural Dynamics of SARS-CoV-2 NSP4 C-terminal Domain and Implications for Viral Processing
Lingshen Meng1, Shangxiang Ye1, Kai Pei2
1Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Journal of Molecular Biology
|August 5, 2025
Summary
Coronaviruses like SARS-CoV-2 require viral protein processing for maturation. Targeting the dynamic NSP4 C-terminal domain offers a novel strategy against these viruses.
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- Coronaviruses, including SARS-CoV-2, are significant global health threats.
- Proteolytic processing of viral polyproteins into functional nonstructural proteins (NSPs) is crucial for viral maturation.
- NSP4 is cleaved by the main protease, NSP5, to release mature components.
Purpose of the Study:
- To investigate the conformational dynamics of the NSP4 C-terminal domain (NSP4-CTD).
- To understand how NSP4-CTD dynamics influence the autoprocessing mediated by NSP5.
- To identify novel therapeutic targets for coronavirus antiviral interventions.
Main Methods:
- Integrative approach combining X-ray crystallography, NMR spectroscopy, and molecular dynamics simulations.
- Analysis of NSP4-CTD conformational states and their interconversion.
- Assessment of the role of the C-terminal tail in NSP4-NSP5 interaction and autoprocessing efficiency.
Main Results:
- NSP4-CTD dynamically interconverts among multiple conformational states (undocked, docked extended, docked helical).
- Formation of the C-terminal helix is sequence and structure-dependent.
- NSP4-CTD conformation modulates NSP4 positioning relative to NSP5, affecting autoprocessing efficiency.
Conclusions:
- The dynamic NSP4 C-terminal tail is a critical regulator of viral polyprotein processing.
- Targeting the dynamic NSP4 C-terminal tail represents a promising novel antiviral strategy against coronaviruses.
- This contrasts with current strategies focusing solely on the NSP5 protease.
Related Concept Videos
02:28Leaky Scanning
5.2K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.2K
00:56Viral Structure
63.8K
Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
63.8K
02:50Conjugated Proteins
18.5K
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
18.5K
01:26Size and Structure of Viral Genomes
145
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
145
01:43SNAREs and Membrane Fusion
11.1K
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
11.1K
01:29Viruses with RNA Genomes
121
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
121