G-quadruplex forming sequences in the genome of all known human viruses: a comprehensive guide

Enrico Lavezzo; Michele Berselli; Ilaria Frasson; Rosalba Perrone; Giorgio Palù; Alessandra R. Brazzale; Sara N. Richter; Stefano Toppo

The discrepancy between the conservation of G-islands and connecting loops (loop_conservation) is an additional indication on the likeliness of biological implications of a specific G4. A positive loop_conservation value highlights G4-islands more conserved than their connecting loops, suggesting that only the G4 scaffold is required for mechanisms that are important for the virus life cycle, while the loops are dispensable. Considering the high mutation rate of viruses, this type of conservation indicates sequences where G4 formation is most likely essential. Equally conserved G4-islands and loops (loop_conservation value = 0) imply that both the G4 scaffold and connecting loops are potentially relevant for the virus and probably involve interactors that specifically recognize them. In this case, the high sequence conservation, especially in CDS, may depend on the required conservation of that peculiar gene product rather than the presence of a G4 structure. Nonetheless, the option of targeting these conserved G4s for therapeutic purposes remains unaltered and the availability of specific and conserved loops may only enhance the chance of finding selective ligands. Therefore, from this point of view, the 'zero' class is the best scenario for the development of specific drugs. The "negative" loop_conservation value scenario is of less author/funder. All rights reserved. No reuse allowed without permission.