A Multiplatform Chemometric Approach to Modeling of Mosquito Repellents

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A multiplatform chemometric approach has an outstanding roll in pharmacology and

chemistry for characterization and design of biologically active compounds (Kovaˇcevi´c et

al. 2019; Vuki´c et al. 2019; Kovaˇcevi´c et al. 2018a; Kovaˇcevi´c et al. 2018b; Jevri´c et al.

2017; Karadži´c et al. 2017a; Karadži´c et al. 2017b; Kovaˇcevi´c et al. 2016a; Kovaˇcevi´c et

al. 2016b; Karadži´c et al. 2015a; Karadži´c et al. 2015b). Nowadays, chemometrics, math-

ematical modeling and molecular docking are essential and valuable tools in the initial

stages of the repelling compounds development. Since mosquitos rapidly develop resis-

tance to repelling compounds, it is necessary to involve various chemometric techniques

in order to shorten the time for laboratory experiments and to save resources in the search

for new highly-effective repelling compounds. Multiple linear regression (MLR), princi-

pal component regression (PCR), partial least squares (PLS) and artificial neural networks

(ANN), together with pattern recognition techniques such as principal component analy-

sis (PCA) and hierarchical cluster analysis (HCA) as well as molecular docking approach

(Kovaˇcevi´c et al. 2020a; Kovaˇcevi´c et al. 2020b; Karadži´c Banjac et al. 2019) can be used

for virtual screening of a large number of compounds with potential repelling properties

and prediction of biological activity or different physicochemical properties of novel or not

yet synthesized or tested repellents or pesticides for prevention of VBD.

All of these methods form a powerful multiplatform for design, selection, testing and

application of novel safe and effective compounds with desired repellent activity. A signif-

icant attention is also paid to the vector modeling (Rashkov 2021; Rashkov et al. 2019).

The epidemiological models have an important role in understanding the spread pattern of

the infectious diseases and evaluating different control treatments such as vector control or

vaccination.

9.2

REPELLING COMPOUNDS IN THE SPOTLIGHT

The use of mosquito repellents is an important tactic worldwide considering that

mosquitos transmit pathogens that cause various VBD (Zika, dengue, malaria, chikun-

gunya, West Nile yellow fever, etc). Repellents are a chemical-based vector control de-

signed to act locally or at the appointed distance to deter insects from biting humans or an-

imals. In the market, there are various kinds of repellent products: textiles (clothes), sprays,

lotions, aerosols, stickers, wristbands, nets and vaccines. Repellents should be designed to

match with specific mosquito species sensitivity for selected repellent, biting time, host

and habitat preferences. Although there are many commercially available products, scien-

tists all over the world are making great efforts to discover new repelling compounds that

are both effective and safe for use. Until today, N,N-diethyl-3-methylbenzamide (DEET)

is observed as a “golden standard” used for repellent candidates comparison in research

activities to obtain long-lasting repellency (Bohbot et al. 2014).

Chemically-based repellents can be on natural or synthetic basis. Many studies report

that different plant extracts and essential oils express larvicidal, adulticidal and repellent

activities (Ghosh et al. 2021; Sharma et al. 2021; Wu et al. 2019; Zhu et al. 2018; Costa et

al. 2017; Das et al. 2015). Recent research of the larvicidal, adulticidal and repellent activ-

ities of Origanum vulgare L. and Thymus vulgaris L. essential oils against Aedes aegypti