Identification of novel bioinspired synthetic mosquito repellents by combined ligand-based screening and OBP-structure-based molecular docking

A - Papers appearing in refereed journals

Thireou, T., Kythreoti, G., Tsitsanou, K. E., Koussis, K., Drakou, C. E., Kinnersley, J., Kröber, T., Guerin, P. M., Zhou, J-J., Iatrou, K., Eliopoulos, E. and Zographos, S. E. 2018. Identification of novel bioinspired synthetic mosquito repellents by combined ligand-based screening and OBP-structure-based molecular docking. Insect Biochemistry and Molecular Biology. 98 (July), pp. 48-61.

AuthorsThireou, T., Kythreoti, G., Tsitsanou, K. E., Koussis, K., Drakou, C. E., Kinnersley, J., Kröber, T., Guerin, P. M., Zhou, J-J., Iatrou, K., Eliopoulos, E. and Zographos, S. E.
Abstract

In this work we report a fast and efficient virtual screening protocol for discovery of novel bioinspired synthetic mosquito repellents with lower volatility and, in all likelihood, increased protection time as compared with their plant-derived parental compounds. Our screening protocol comprises two filtering steps. The first filter is based on the shape and chemical similarity to known plant-derived repellents, whereas the second filter is based on the predicted similarity of the ligand's binding mode to the Anopheles gambiae odorant binding protein (AgamOBP1) relative to that of DEET and Icaridin to the same OBP. Using this protocol, a chemical library containing 42,755 synthetic molecules was screened in silico and sixteen selected compounds were tested for their affinity to AgamOBP1 in vitro and repellence against A. gambiae female mosquitoes using a warm-body repellent assay. One of them showed DEET-like repellence (91%) but with significantly lower volatility (2.84 × 10−6 mmHg) than either DEET (1.35 × 10−3 mmHg) or its parental cuminic acid (3.08 × 10−3 mmHg), and four other compounds were found to exhibit repellent indices between 69 and 79%. Overall, a correlation was not evident between repellence and OBP-binding strength. In contrast, a correlation between binding mode and repellence was found.

KeywordsMosquito repellent; Odorant-binding protein; Virtual screening; Shape similarity; Molecular docking; Warm-body behavioral assay
Year of Publication2018
JournalInsect Biochemistry and Molecular Biology
Journal citation98 (July), pp. 48-61
Digital Object Identifier (DOI)doi:10.1016/j.ibmb.2018.05.001
Open accessPublished as non-open access
Funder project or codeENAROMaTIC
FunderEuropean Commission - EC
Output statusPublished
Publication dates
Online08 May 2018
Publication process dates
Accepted07 May 2018
Copyright licensePublisher copyright
PublisherElsevier
Pergamon-Elsevier Science Ltd
Grant IDGA-222927
FP7- HEALTH-2007-2.3.2.9
ISSN0965-1748

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