Non-structural protein 1 (Nsp1) represents one of the most crucial SARS-CoV-2 virulence factors by inhibiting the translation of host mRNAs and promoting their degradation. We selected naturally occurring virus lineages with specific Nsp1 deletions located at both the N- and C-terminus of the protein. Our data provide new insights into how Nsp1 coordinates these functions on host and viral mRNA recognition. Residues 82–85 in the N-terminal part of Nsp1 likely play a role in docking the 40S mRNA entry channel, preserving the inhibition of host gene expression without affecting cellular mRNA decay. Furthermore, this domain prevents viral mRNAs containing the 5′-leader sequence to escape translational repression. These findings support the presence of distinct domains within the Nsp1 protein that differentially modulate mRNA recognition, translation and turnover. These insights have implications for the development of drugs targeting viral proteins and provides new evidences of how specific mutations in SARS-CoV-2 Nsp1 could attenuate the virus.

Gori Savellini, G., Anichini, G., Manetti, F., Trivisani, C.I., Cusi, M.G. (2024). Deletion of 82–85 N-Terminal Residues in SARS-CoV-2 Nsp1 Restricts Virus Replication. VIRUSES, 16(5) [10.3390/v16050689].

Deletion of 82–85 N-Terminal Residues in SARS-CoV-2 Nsp1 Restricts Virus Replication

Gori Savellini, Gianni
;
Anichini, Gabriele;Manetti, Fabrizio;Trivisani, Claudia Immacolata;Cusi, Maria Grazia
2024-01-01

Abstract

Non-structural protein 1 (Nsp1) represents one of the most crucial SARS-CoV-2 virulence factors by inhibiting the translation of host mRNAs and promoting their degradation. We selected naturally occurring virus lineages with specific Nsp1 deletions located at both the N- and C-terminus of the protein. Our data provide new insights into how Nsp1 coordinates these functions on host and viral mRNA recognition. Residues 82–85 in the N-terminal part of Nsp1 likely play a role in docking the 40S mRNA entry channel, preserving the inhibition of host gene expression without affecting cellular mRNA decay. Furthermore, this domain prevents viral mRNAs containing the 5′-leader sequence to escape translational repression. These findings support the presence of distinct domains within the Nsp1 protein that differentially modulate mRNA recognition, translation and turnover. These insights have implications for the development of drugs targeting viral proteins and provides new evidences of how specific mutations in SARS-CoV-2 Nsp1 could attenuate the virus.
2024
Gori Savellini, G., Anichini, G., Manetti, F., Trivisani, C.I., Cusi, M.G. (2024). Deletion of 82–85 N-Terminal Residues in SARS-CoV-2 Nsp1 Restricts Virus Replication. VIRUSES, 16(5) [10.3390/v16050689].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1260997