Crystal structure of the NS3-like helicase from Alongshan virus

Xiaopan Gao; Kaixiang Zhu; Justyna Aleksandra Wojdyla; Pu Chen; Bo Qin; Ziheng Li; Meitian Wang; Sheng Cui

doi:10.1107/S2052252520003632

Crystal structure of the NS3-like helicase from Alongshan virus

IUCrJ. 2020 Apr 10;7(Pt 3):375-382. doi: 10.1107/S2052252520003632. eCollection 2020 May 1.

Authors

Xiaopan Gao¹, Kaixiang Zhu¹, Justyna Aleksandra Wojdyla², Pu Chen¹, Bo Qin¹, Ziheng Li¹, Meitian Wang², Sheng Cui¹

Affiliations

¹ NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People's Republic of China.
² Swiss Light Source at the Paul Scherrer Institute, CH-5232 Villigen, Switzerland.

Abstract

Alongshan virus (ALSV) is an emerging human pathogen that was identified in China and rapidly spread to the European continent in 2019, raising concerns about public health. ALSV belongs to the distinct Jingmenvirus group within the Flaviviridae family with segmented RNA genomes. While segments 2 and 4 of the ALSV genome encode the VP1-VP3 proteins of unknown origin, segments 1 and 3 encode the NS2b-NS3 and NS5 proteins, which are related to Flavivirus nonstructural proteins, suggesting an evolutionary link between segmented and unsegmented viruses within the Flaviviridae family. Here, the enzymatic activity of the ALSV NS3-like helicase (NS3-Hel) was characterized and its crystal structure was determined to 2.9 Å resolution. ALSV NS3-Hel exhibits an ATPase activity that is comparable to those measured for Flavivirus NS3 helicases. The structure of ALSV NS3-Hel exhibits an overall fold similar to those of Flavivirus NS3 helicases. Despite the limited amino-acid sequence identity between ALSV NS3-Hel and Flavivirus NS3 helicases, structural features at the ATPase active site and the RNA-binding groove remain conserved in ALSV NS3-Hel. These findings provide a structural framework for drug design and suggest the possibility of developing a broad-spectrum antiviral drug against both Flavivirus and Jingmenvirus.

Keywords: Alongshan virus; Flavivirus; NS3-like helicase; segmented viruses.

Grants and funding

This work was funded by Natural Science Foundation of Beijing Municipality grants 7182117 and 7174288. National Major Science and Technology Projects of China grant 2018ZX10101001. National Natural Science Foundation of China grants 81572005, 81772207, 81971985, 11775308, and 81802057. China Academy of Chinese Medical Sciences grants 2017-I2M-1-014, 2016-I2M-1-013, 2018PT51009, and 2017PT31049.