Identification of the SARS-unique domain of SARS-CoV-2 as an antiviral target

Bo Qin, Ziheng Li, Kaiming Tang, Tongyun Wang, Yubin Xie, Sylvain Aumonier, Meitian Wang, Shuofeng Yuan () and Sheng Cui ()
Additional contact information
Bo Qin: Institute of Pathogen Biology Chinese Academy of Medical Sciences & Peking Union Medical College
Ziheng Li: Institute of Pathogen Biology Chinese Academy of Medical Sciences & Peking Union Medical College
Kaiming Tang: The University of Hong Kong
Tongyun Wang: The University of Hong Kong
Yubin Xie: The University of Hong Kong
Sylvain Aumonier: Swiss Light Source at the Paul Scherrer Institute
Meitian Wang: Swiss Light Source at the Paul Scherrer Institute
Shuofeng Yuan: The University of Hong Kong
Sheng Cui: Institute of Pathogen Biology Chinese Academy of Medical Sciences & Peking Union Medical College

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract SARS-CoV-2 nsp3 is essential for viral replication and host responses. The SARS-unique domain (SUD) of nsp3 exerts its function through binding to viral and host proteins and RNAs. Herein, we show that SARS-CoV-2 SUD is highly flexible in solution. The intramolecular disulfide bond of SARS-CoV SUD is absent in SARS-CoV-2 SUD. Incorporating this bond in SARS-CoV-2 SUD allowed crystal structure determination to 1.35 Å resolution. However, introducing this bond in SARS-CoV-2 genome was lethal for the virus. Using biolayer interferometry, we screened compounds directly binding to SARS-CoV-2 SUD and identified theaflavin 3,3’-digallate (TF3) as a potent binder, Kd 2.8 µM. TF3 disrupted the SUD-guanine quadruplex interactions and exhibited anti-SARS-CoV-2 activity in Vero E6-TMPRSS2 cells with an EC50 of 5.9 µM and CC50 of 98.5 µM. In this work, we provide evidence that SARS-CoV-2 SUD harbors druggable sites for antiviral development.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-39709-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39709-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-39709-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().