| Summary: | Background: Mosquito galactose-specific C-type lectins (mosGCTLs), such as mosGCTL-1, act as ligands to facilitate the invasion of flaviviruses like West Nile virus (WNV). WNV interacts with the <i>mosGCTL-1</i> of <i>Aedes aegypti</i> (Culicidae) and facilitates the invasion of this virus. Nevertheless, there is no data about the role of mosGCTL-1 as a transmission-blocking vaccine candidate in <i>Culex pipiens</i>, the most abundant Culicinae mosquito in temperate regions. Methods: Adult female <i>Cx. pipiens</i> mosquitoes were experimentally infected with a WNV infectious blood meal, and the effect of rabbit anti-rmosGCTL-1 antibodies on virus replication was evaluated. Additionally, in silico studies such as the prediction of protein structure, homology modeling, and molecular interactions were carried out. Results: We showed a 30% blocking activity of <i>Cx. pipiens mosGCTL-1</i> polyclonal antibodies (compared to the 10% in the control group) with a decrease in infection rates in mosquitoes at day 5 post-infection, suggesting that there may be other proteins in the midgut of <i>Cx. pipiens</i> that could act as cooperative-receptors for WNV. In addition, docking results revealed that WNV binds with high affinity, to the <i>Culex</i> mosquito lectin receptors. Conclusions: Our results do not support the idea that mosGCTL-1 of <i>Cx. pipiens</i> primarily interacts with WNV to promote viral infection, suggesting that other mosGCTLs may act as primary infection factors in <i>Cx. pipiens.</i>
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