Publication:
Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro

1

Issued Date

2021-12-01

Resource Type

Article

ISSN

20452322

DOI

10.1038/s41598-021-99152-9

Other identifier(s)

2-s2.0-85116550155

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Scientific Reports. Vol.11, No.1 (2021)

Suggested Citation

Steven P. Maher, Amélie Vantaux, Victor Chaumeau, Adeline C.Y. Chua, Caitlin A. Cooper, Chiara Andolina, Julie Péneau, Mélanie Rouillier, Zaira Rizopoulos, Sivchheng Phal, Eakpor Piv, Chantrea Vong, Sreyvouch Phen, Chansophea Chhin, Baura Tat, Sivkeng Ouk, Bros Doeurk, Saorin Kim, Sangrawee Suriyakan, Praphan Kittiphanakun, Nana Akua Awuku, Amy J. Conway, Rays H.Y. Jiang, Bruce Russell, Pablo Bifani, Brice Campo, François Nosten, Benoît Witkowski, Dennis E. Kyle Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro. Scientific Reports. Vol.11, No.1 (2021). doi:10.1038/s41598-021-99152-9 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/79208

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Title

Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro

Author(s)

Steven P. Maher
 Amélie Vantaux
 Victor Chaumeau
 Adeline C.Y. Chua
 Caitlin A. Cooper
 Chiara Andolina
 Julie Péneau
 Mélanie Rouillier
 Zaira Rizopoulos
 Sivchheng Phal
 Eakpor Piv
 Chantrea Vong
 Sreyvouch Phen
 Chansophea Chhin
 Baura Tat
 Sivkeng Ouk
 Bros Doeurk
 Saorin Kim
 Sangrawee Suriyakan
 Praphan Kittiphanakun
 Nana Akua Awuku
 Amy J. Conway
 Rays H.Y. Jiang
 Bruce Russell
 Pablo Bifani
 Brice Campo
 François Nosten
 Benoît Witkowski
 Dennis E. Kyle

Other Contributor(s)

Faculty of Tropical Medicine, Mahidol University
 Institut Pasteur du Cambodge
 University of South Florida Health
 London School of Hygiene & Tropical Medicine
 University of Georgia
 NUS Yong Loo Lin School of Medicine
 Agency for Science, Technology and Research, Singapore
 University of Otago
 Nuffield Department of Medicine
 Medicines for Malaria Venture

Abstract

Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade.

Keyword(s)

Multidisciplinary

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URI

https://repository.li.mahidol.ac.th/handle/123456789/79208

Collections

Scopus 2021