Rational design of 2H-chromene-based antiphytovirals that inhibit virion assembly by outcompeting virus capsid-RNA interactions
Xiong Yang,
Deguo Liu,
Chunle Wei,
Jianzhuan Li,
Chunni Zhao,
Yanping Tian,
Xiangdong Li,
Baoan Song,
Runjiang Song
Affiliations
Xiong Yang
National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals of Guizhou University, Guiyang City, Guizhou Province 550025, P.R. China
Deguo Liu
College of Plant Protection, Shandong Agricultural University, Tai’an City, Shandong Province 271018, P.R. China
Chunle Wei
National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals of Guizhou University, Guiyang City, Guizhou Province 550025, P.R. China
Jianzhuan Li
National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals of Guizhou University, Guiyang City, Guizhou Province 550025, P.R. China
Chunni Zhao
National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals of Guizhou University, Guiyang City, Guizhou Province 550025, P.R. China
Yanping Tian
College of Plant Protection, Shandong Agricultural University, Tai’an City, Shandong Province 271018, P.R. China; Corresponding author
Xiangdong Li
College of Plant Protection, Shandong Agricultural University, Tai’an City, Shandong Province 271018, P.R. China
Baoan Song
National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals of Guizhou University, Guiyang City, Guizhou Province 550025, P.R. China
Runjiang Song
National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals of Guizhou University, Guiyang City, Guizhou Province 550025, P.R. China; Corresponding author
Summary: Although the determination of the structural basis of potato virus Y (PVY) coat protein (CP) provides the possibility for CP-based antiviral drug design, the role of many specific residues on CP in regulating virion pathogenicity is largely unknown, and fewer small-molecular drugs have been discovered to act on these potential sites. In this study, a series of derivatives of 2,2-dimethyl-2H-chromene are rationally designed by employing a molecular hybridization strategy. We screen a case of phytovirucide C50 that could form a stable H-bond with Ser125 of PVY CP to exert antiviral properties. Ser125 is further identified to be crucial for CP-viral RNA (vRNA) interaction, enabling PVY virion assembly. This interaction can be significantly inhibited through competitive binding with compound C50. The study enhances our understanding of anti-PVY drug mechanisms and provides a basis for developing new CP-targeting virus particle assembly inhibitors.
