Whole-Cell Phenotypic Screening of Medicines for Malaria Venture Pathogen Box Identifies Specific Inhibitors of Plasmodium falciparum Late-Stage Development and Egress

Author:

Patra Alok Tanala1ORCID,Hingamire Tejashri23,Belekar Meenakshi A.23,Xiong Aoli4,Subramanian Gowtham1ORCID,Bozdech Zbynek5,Preiser Peter5,Shanmugam Dhanasekaran23ORCID,Chandramohanadas Rajesh1ORCID

Affiliation:

1. Pillar of Engineering Product Development (EPD), Singapore University of Technology and Design (SUTD), Singapore

2. Biochemical Sciences Division, CSIR National Chemical Laboratory, Pune, India

3. Academy of Scientific and Innovative Research, Ghaziabad, India

4. BioSystems and Micromechanics (BioSyM)—IRG, Singapore MIT Alliance for Research & Technology Centre, Singapore

5. School of the Biological Sciences, Nanyang Technological University, Singapore

Abstract

We report a systematic, cellular phenotype-based antimalarial screening of the Medicines for Malaria Venture Pathogen Box collection, which facilitated the identification of specific blockers of late-stage intraerythrocytic development of Plasmodium falciparum . First, from standard growth inhibition assays, we identified 173 molecules with antimalarial activity (50% effective concentration [EC 50 ] ≤ 10 μM), which included 62 additional molecules over previously known antimalarial candidates from the Pathogen Box.

Funder

Department of Science and Technology, Ministry of Science and Technology, India

Agency for Science, Technology and Research

Singapore University of Technology and Design

Marsden Fund

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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