LDL receptor in alphavirus entry: structural analysis and implications for antiviral therapy

Ningning Wang; Andres Merits; Michael Veit; Laura Sandra Lello; Shuhan Kong; Houqi Jiao; Jie Chen; Yu Wang; Georgi Dobrikov; Félix A Rey; Shuo Su

doi:10.1038/s41467-024-49301-1

LDL receptor in alphavirus entry: structural analysis and implications for antiviral therapy

Nat Commun. 2024 Jun 8;15(1):4906. doi: 10.1038/s41467-024-49301-1.

Authors

Ningning Wang^#¹, Andres Merits^#², Michael Veit^#³, Laura Sandra Lello^#², Shuhan Kong¹, Houqi Jiao¹, Jie Chen¹, Yu Wang¹, Georgi Dobrikov⁴, Félix A Rey⁵, Shuo Su^{6

7}

Affiliations

¹ Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing, China.
² Institute of Bioengineering, University of Tartu, Nooruse Street 1, Tartu, Estonia.
³ Institute for Virology, Center for Infection Medicine, Veterinary Faculty, Free University Berlin, Berlin, Germany.
⁴ Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Bl. 9, Sofia, Bulgaria.
⁵ Institut Pasteur, Unité de Virologie Structurale, Department Virologie, CNRS UMR 3569, 25-28 Rue du Docteur Roux, 75724 Paris Cedex 15, Paris, France.
⁶ Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing, China. shuosu@njau.edu.cn.
⁷ Sanya Institute of Nanjing Agricultural University, Nanjing Agricultural University, Sanya, China. shuosu@njau.edu.cn.

^# Contributed equally.

Abstract

Various low-density lipoprotein receptors (LPRs) have been identified as entry factors for alphaviruses, and structures of the corresponding virion-receptor complexes have been determined. Here, we analyze the similarities and differences in the receptor binding modes of multiple alphaviruses to understand their ability to infect a wide range of hosts. We further discuss the challenges associated with the development of broad-spectrum treatment strategies against a diverse range of alphaviruses.

MeSH terms

Alphavirus Infections / drug therapy
Alphavirus Infections / virology
Alphavirus* / drug effects
Alphavirus* / genetics
Alphavirus* / physiology
Animals
Antiviral Agents* / pharmacology
Antiviral Agents* / therapeutic use
Humans
Protein Binding
Receptors, LDL* / genetics
Receptors, LDL* / metabolism
Receptors, Virus / chemistry
Receptors, Virus / metabolism
Virion / metabolism
Virus Internalization* / drug effects

Substances

Antiviral Agents
Receptors, LDL
Receptors, Virus