Svetlana Glushakova and Joshua Zimmerberg, PNAS June 29, 2021 118 (26

Figure: Dr. Glushakova; National Institute of Health

A once in a century new viral outbreak, COVID-19, has caused unfathomable numbers of deaths, toward 4 million. Yet an ancient disease, malaria, endemic to the residents of more than half of Earth, is even more devastating than this pandemic over time: It caused about 12 million deaths in the last 20 y alone, with estimates of tens of millions of deaths in the preceding three decades (1). Arguably the “most successful human pathogen,” the unicellular malaria parasites of the Plasmodium species are a medical and socioeconomic scourge in the zones of their transmission by female Anopheles mosquitoes, mostly sub-Saharan Africa, South Asia, and South America. Considering the number of people at risk to contract malaria, even a highly efficient vaccine would take years to roll out in these countries, during which time unvaccinated people would contract billions of new infections with millions of deaths. In addition, parasites escaping immune block in vaccinated people must be stopped by drug treatment shortly after initiation of the erythrocytic cycle of replication, the part of the parasite life cycle causing malaria, which is capable of killing people within 1 d to 2 d after appearance of symptoms. Continuous attempts at vaccine development are going on, now mostly to block parasites before they ever reach erythrocytes (2). The surge in deaths cited above can be traced to the development of parasite resistance to the affordable drug chloroquine (3). Artemisinin, a newer, powerful, and affordable antimalarial drug, seemed promising at first, but resistant strains now abound (4). Thus, the search for new antimalarial drugs will be a perpetual task until multitargeted drug mixtures are joined by vigorous antimosquito efforts and efficient, affordable, and heat-resistant vaccines identified by the World Health Organization to eliminate malaria. The impressive research reported by Lidumniece et al. (5), “Peptidic boronic acids are potent cell-permeable inhibitors of the malaria parasite egress serine protease SUB1,” is a leap forward in a large and persistent effort to develop a drug against a crucial but as yet undrugged stage of the parasite’s replication: egress of daughter parasites from infected erythrocytes.

See more: https://www.pnas.org/content/118/26/e2108103118