Identification of New Compounds against PRRSV Infection by Directly Targeting CD163
Jiaqi Zhu, Xin He, Denzil Bernard, Jianing Shen, Yue Su, Andrew Wolek, Brianna Issacs, Neha Mishra, Xiuchun Tian, Antonio E. Garmendia, Young Tang
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses to the swine industry worldwide. Current vaccines cannot provide cross protection against different strains, and there are no effective treatments available to hamper the spread of this disease. In this study, we identified a group of new small molecules that can inhibit the PRRSV interaction with its specific receptor CD163 and dramatically block the infection of both types 1 and type 2 PRRSVs to host cells. We also demonstrated the physical association of these compounds with the SRCR5 domain of CD163. In addition, molecular docking and structure-activity relationship analyses provided new insights for the CD163/PRRSV glycoprotein interaction and further improvement of these compounds against PRRSV infection.