BRACO-19 targeted the G-quadruplex in the 3′UTR of the Cucumber mosaic virus 1a, 2b, and CP genes to inhibit viral proliferation

Abstract

Background

The development of highly efficient and environmentally friendly plant virus inhibitors with novel structures mostly depends on the discovery of new targets. G-quadruplexes are non-classical high-level structures that are formed by guanine-rich nucleic acid sequences, which have significant biological functions. Small molecules that target the G-quadruplexes in the genomes of animal viruses have been shown to inhibit viral proliferation. However, the structure and function of the G-quadruplex in the plant virus genome have rarely been reported. Investigating the function of plant virus G-quadruplexes facilitates the discovery of new targets for screening viral inhibitors.

Results

In this study, we found that the 3′-end untranslated regions (3′UTRs) of cucumber mosaic virus (CMV) 1a, 2b, and CP genes all contain a putative G-quadruplex sequence (PQS) composed of the same base sequence, which was identified to fold into a G-quadruplex structure (CMV-3′UTR-PQS). In comparison to other G-quadruplex ligands, BRACO-19 exhibited the strongest binding affinity for the CMV-3′UTR-PQS. Further studies revealed BRACO-19 increased the ability of CMV-3′UTR-PQS to inhibit the expression of gene and exhibited an excellent anti-CMV activity. Moreover, BRACO-19 was found to induce the formation of intermolecular G-quadruplex structure from intramolecular G-quadruplex in CMV-3′UTR-PQS, and shifted the balance of the conformational ensemble of CMV-3′UTR-PQS in the direction of the compact conformation.

Conclusion

This study suggested that CMV-3′UTR-PQS can be used as a target for screening viral inhibitors and provided new strategies for CMV prevention and control. © 2025 Society of Chemical Industry.