Alendronate repositioning as potential anti-parasitic agent targeting Trichinella spiralis inorganic pyrophosphatase,...

Trichinellosis represents great public health and economic problems worldwide. Moreover, the development of parasitic resistance against conventional anthelminthic treatment led to the urgent search for new therapeutic strategies, including drug repurposing. Bisphosphonates have been used to inhibit the growth of many parasites and have also emerged as promising candidates for the treatment of cryptosporidiosis and amoebic liver abscess. Alendronate is a second-generation bisphosphonate that is widely used for the treatment and prevention of osteoporosis. Till date, there is not enough data on the effect of this drug on Trichinella spiralis and it is unknown whether the regular use of this drug in osteoporotic patients may alter the course of the infection. ALN showed a significant lethal effect on both adult worms and juveniles, with severe tegumental damage in the form of fissures in the cuticle, widening of the hypodermal gland, and flattening of the cuticular annulation, ending with the appearance of multiple vesicles and large cauliflower masses. Molecular docking outcomes unveiled the potential inhibition of ALN against T. spiralis surface proteins (i.e., Ts-SP, Ts-PPase, Ts-MAPRC2, Ts-TS, Ts-MIF, etc.), with promising results confirmed its ability to defeat T. spiralis via targeting its surface proteins. Moreover, molecular dynamics simulation, through the analysis of RMSD, RMSF, RG, SASA and cluster analysis, proved the prolonged effective inhibition of ALN on T. spiralis inorganic pyrophosphatase, as an essential surface protein required for molting and developmental process of intestinal larval stages. Thus, ALN might be a valuable drug candidate for the treatment of trichinellosis and warrant further investigation in animal models of disease.