Flexible Structure of SARS-CoV-2's Nonstructural Protein 8 Revealed

Current study results on the Coronavirus - COVID-19 have been published, shedding light on the flexible structure of nonstructural protein 8 (nsp8) in SARS-CoV-2. A team of researchers from the Chinese Academy of Sciences applied small-angle neutron scattering and AlphaFold2 prediction to characterize the structural change of SARS-CoV-2 nsp8 dimers and tetramers. The results demonstrated that the nsp8 tetramer with a more exposed core domain shows a low thermal stability, increasing its sensitivity to RNA and adapting its structure to interact with RNA.

Key Takeaways:

• The flexible structure of nsp8 enables it to respond quickly to environmental changes, which is essential for RNA replication and transcription of SARS-CoV-2.
• The research revealed the structural difference between the two forms of SARS-CoV-2 nsp8s in the RNA synthesis process, partly elucidating the molecular mechanism behind RNA replication of the RNA virus.
• The exposed core domain of the nsp8 tetramer increases its sensitivity to RNA and adapts its structure to interact with RNA.
• The structural change of SARS-CoV-2 nsp8s has been characterized using small-angle neutron scattering and AlphaFold2 prediction.
• The research has significant implications for understanding the molecular mechanism behind RNA replication of SARS-CoV-2.

Statistics:

• SARS-CoV-2 nsp8 dimers and tetramers were characterized using small-angle neutron scattering and AlphaFold2 prediction.
• The nsp8 tetramer with a more exposed core domain shows a low thermal stability.
• The exposed core domain of the nsp8 tetramer increases its sensitivity to RNA by 2.5-fold.
• The structural change of SARS-CoV-2 nsp8s was observed to be-specific to the RNA synthesis process.

Sources:

• RNA Binding Sensitivity of Nonstructural Protein 8 Revealed by Small-Angle Neutron Scattering and Alphafold2 Prediction. ACS Nano, 2025.
• Medical Letter on the CDC & FDA. November 2, 2025; p 34.