SARS-CoV-2 nsp16 is regulated by host E3 ubiquitin ligases, UBR5 and MARCHF7 DOI Open Access
Tian Li, Zongzheng Zhao, Wenying Gao

et al.

Published: Dec. 24, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for disease 2019 (COVID-19), remains a global public health threat with major economic implications. The non-structural protein 16 (nsp16) of SARS-CoV-2, in complex nsp10, catalyses final step viral mRNA capping via its 2’-O-methylase activity, enabling to evade host immunity and protect from degradation. However, factors regulating nsp16 have not been thoroughly explored. Although various E3 ubiquitin ligases are known interact SARS-CoV-2 proteins, their specific roles targeting degradation remain unclear. In this study, we demonstrate that is ubiquitinated degraded by UBR5 MARCHF7, acting through ubiquitin-proteasome system (UPS). MARCHF7 induce K48- K27-linked ubiquitination, respectively, independent processes inhibit replication both vitro vivo. Furthermore, exhibited broad-spectrum antiviral activity degrading variants different strains. Our findings uncover novel mechanisms which UPS antagonises provide promising targets therapeutic intervention against COVID-19.

Language: Английский

SARS-CoV-2 nsp16 is regulated by host E3 ubiquitin ligases, UBR5 and MARCHF7 DOI Open Access
Tian Li, Zirui Liu, Wenying Gao

et al.

Published: Dec. 24, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for disease 2019 (COVID-19), is a global public health threat with significant economic burden. The non-structural protein 16 (nsp16) of SARS-CoV-2, in complex nsp10, catalyses final step viral mRNA capping via its 2’-O-methylase activity. This function helps evade host immunity and protect from degradation. Current literature has not thoroughly investigated factors that regulate nsp16. Although various E3 ubiquitin ligases are known to interact SARS-CoV-2 proteins, their specific roles targeting nsp16 degradation have been elucidated. Here, we demonstrate ubiquitinated degraded by UBR5 MARCHF7, acting through ubiquitin-proteasome system (UPS). MARCHF7 induce K48-and K27-linked ubiquitination, respectively. Moreover, this either or independent, both processes inhibit replication vitro as well vivo. Further, exhibited broad-spectrum antiviral potential degrading variants different strains. Our findings provide novel insights into role UPS antagonising open new avenues therapeutic interventions against COVID-19.

Language: Английский

Citations

0
SARS-CoV-2 nsp16 is regulated by host E3 ubiquitin ligases, UBR5 and MARCHF7 DOI Open Access
Tian Li, Zongzheng Zhao, Wenying Gao

et al.

Published: Dec. 24, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for disease 2019 (COVID-19), remains a global public health threat with major economic implications. The non-structural protein 16 (nsp16) of SARS-CoV-2, in complex nsp10, catalyses final step viral mRNA capping via its 2’-O-methylase activity, enabling to evade host immunity and protect from degradation. However, factors regulating nsp16 have not been thoroughly explored. Although various E3 ubiquitin ligases are known interact SARS-CoV-2 proteins, their specific roles targeting degradation remain unclear. In this study, we demonstrate that is ubiquitinated degraded by UBR5 MARCHF7, acting through ubiquitin-proteasome system (UPS). MARCHF7 induce K48- K27-linked ubiquitination, respectively, independent processes inhibit replication both vitro vivo. Furthermore, exhibited broad-spectrum antiviral activity degrading variants different strains. Our findings uncover novel mechanisms which UPS antagonises provide promising targets therapeutic intervention against COVID-19.

Language: Английский

Citations

0