Finally, we believe that our findings shed light on the potential of covalent kinase inhibitors as a novel strategy for malaria treatment. To the best of our knowledge, chloroacetamide 4 represents the first covalent kinase inhibitor of malaria, as well as a rare example of a covalent inhibitor of a non-human kinase. By targeting essential malarial protein kinases such as PfCLK3, covalent inhibitors offer a promising avenue for the development of safe and effective antimalarials with curative, transmission-blocking, and prophylactic properties. Further preclinical and clinical studies are warranted to validate the efficacy and safety of these compounds, with the ultimate goal of advancing towards global eradication of malaria.