Rapid Fire Presentation 8th International Conference on Plasmodium vivax Research 2022

Plasmodium Vivax: progress in screening and impact on Drug Discovery and Development (#307)

Brice Campo 1 , Zaira Rizopoulos 1 , Steven Maher 2 , Chet Joyner 2 , Dennis Kyle 2 , Amelie Vantaux 3 , Benoit Witkowski 3 , Karl A Kudyba 4 , Alison E Roth 4 , Sara Viera-Morilla 5 , Maria Jose Lafuente-Monasterio 5 , Maria Santos Martinez-Martinez 5 , Javier F Gamo 5
  1. MMV, Geneva, GENEVA, Switzerland
  2. University of Georgia Athens – UGA, Athens,, USA
  3. Institut Pasteur du Cambodge – IPC, Phnom Penh, Cambodia
  4. Walter Reed Army Institute of Research – WRAIR, Silver Springs, USA
  5. Glaxosmithkline – GSK, Tres Cantos, Madrid, Spain

P. vivax is the most abundant of the Plasmodium species that infect humans outside Africa. To meet the call for eradication, medicines that block the relapse of P. vivax and eliminate the asymptomatic and hepatic dormant forms (hypnozoites) of P. vivax, without the risk of hemolysis in G6PD-deficient patients need to be developed.

The lack of robust and reliable in vitro P.vivax. liver stage assays has, for a long time, hampered the discovery of such new molecules for radical cure. Tremendous progresses have now been achieved over the last decade through the work of organizations such as Medicines for Malaria Venture (MMV), their partners, and others; the development of high throughput in vitro P. vivax and P. cynomolgi hypnozoite assays has enabled the screening of >200,000 compounds against hypnozoites and the delivery of a new hit to lead series that is part of MMV’s global portfolio of drugs. This presentation will review the hit generation strategy and work to date, including the successes and challenges of screening and identification of series suitable for further optimization.

In addition, the novel hypnozoite screening assays have also been used to test the two approved anti-relapse medicines, primaquine and tafenoquine, and explore the effects of hypnozonticidal activity alone or in combination with other relevant clinical antimalarials. This presentation will summarize the data and relate the findings to observations in clinical studies.