Editorial: Antimalarial chemotherapy in the XXIst century

Plasmodium parasites are known as the etiological agents of malaria, transmitted by Anophelesmosquitoes. Malaria is one of the “Big Three” infectious diseases, alongside HIV-1/ AIDS and Tuberculosis, that are prioritized by the World Health Organization (Bourzac, 2014). While tackling the “Big Three” is an important part of the Sustainable Development Goal 3—GoodHealth andWellbeing—of theUnitedNations Agenda for 2030, the emergence of the COVID-19 pandemic reversed decades of improvements and led to a notable increase in malaria deaths in Sub-Saharan Africa in 2020 (World Health Organization, 2021). Therefore, malaria remains a major health concern worldwide. This accentuates the pressing need to control malaria. The use of insecticide-treated bed nets and artemisinin-based combination therapies (ACTs) have been major strategies in decreasing the malaria burden over the past 2 decades (World Health Organization, 2021). Nevertheless, the emergence of parasite resistance to ACT, now also spread to Africa, is a serious menace to malaria containment and drives the need to find efficient alternatives (Ashley et al., 2014; Uwimana et al., 2020; Balikagala et al., 2021; Noreen et al., 2021; Rosenthal, 2021). This scenario has fueled new approaches towards antimalarial drug discovery and development, causing an impressive enrichment of the antimalarial leads’ portfolio in the XXIst century (Burrows et al., 2011; Burrows et al., 2017; Aguiar et al., 2019). An optimal antimalarial should not elicit resistance and should neutralize all parasite stages inside the human host, namely 1) hepatic forms associated with the asymptomatic onset of disease, 2) dormant liver forms (hypnozoites) responsible for relapse in certain malaria types, 3) blood-stage forms underlying the symptomatic phase of infection, and 4) gametocytes, responsible for host-to-vector transmission. An ideal antimalarial should additionally be produced at a low cost since malaria is mainly endemic in low-to-middleincome countries (Burrows et al., 2017). Besides conventional drug discovery approaches, cost-effective ways to accelerate the identification of novel antimalarial strategies have included 1) combination therapy, by joining two or more known drugs (van der Pluijm et al., 2021), 2) covalent bitherapy, by conjugating different pharmacophores (Odhiambo OPEN ACCESS