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p. falciparum

Development of novel anti-malarial from structurally diverse library of molecules, targeting plant-like CDPK1, a multistage growth regulator of P. falciparum

May 14, 2020 - 12:21 -- Open Access
Jain R, Gupta S, Munde M, Pati S, Singh S
Biochem J. 2020 May 13. pii: BCJ20200045

Upon Plasmodium falciparum merozoites exposure to low [K+] environment in blood plasma, there is escalation of cytosolic [Ca2+] which activates Ca2+-Dependent Protein Kinase 1 (CDPK1), a signaling hub of intra-erythrocytic proliferative stages of parasite. Given its high abundance and multidimensional attributes in parasite life-cycle, this is a lucrative target for desiging antimalarials.

Unsymmetrical Bisquinolines with High Potency against P. falciparum Malaria

May 14, 2020 - 12:18 -- Open Access
Liebman KM, Burgess SJ, Gunsaru B, Kelly JX, Li Y, Morrill W, Liebman MC, Peyton DH
Molecules. 2020 May 10;25(9). pii: E2251

Quinoline-based scaffolds have been the mainstay of antimalarial drugs, including many artemisinin combination therapies (ACTs), over the history of modern drug development. Although much progress has been made in the search for novel antimalarial scaffolds, it may be that quinolines will remain useful, especially if very potent compounds from this class are discovered.

NOT Open Access | Turning the tide: targeting PfCRT to combat drug-resistant P. falciparum

May 7, 2020 - 13:28 -- NOT Open Access
Small-Saunders JL, Hagenah LM, Fidock DA
Nat Rev Microbiol. 2020 May;18(5):261-262

Resistance to the current first-line antimalarials threatens the control of malaria caused by the protozoan parasite Plasmodium falciparum and underscores the urgent need for new drugs with novel modes of action.

NOT Open Access | P. falciparum artemisinin resistance: the effect of heme, protein damage, and parasite cell stress response

April 27, 2020 - 12:51 -- NOT Open Access
Rosenthal MR, Ng CL
ACS Infect Dis. 2020 Apr 23

Despite a significant decline in morbidity and mortality over the last two decades, in 2018 there were 228 million reported cases of malaria and 405,000 malaria-related deaths. Artemisinin, the cornerstone of artemisinin-based combination therapies, is the most potent drug in the antimalarial armamentarium against falciparum malaria. Heme-mediated activation of artemisinin and its derivatives results in widespread parasite protein alkylation, which is thought to lead to parasite death.

Diversity and Multiplicity of P. falciparum infections among asymptomatic school children in Mbita, Western Kenya

April 6, 2020 - 16:08 -- Open Access
Touray AO, Mobegi VA, Wamunyokoli F, Herren JK
Sci Rep. 2020 Apr 3;10(1):5924

Multiplicity of infection (MOI) and genetic diversity of P. falciparum infections are important surrogate indicators for assessing malaria transmission intensity in different regions of endemicity. Determination of MOI and diversity of P. falciparum among asymptomatic carriers will enhance our understanding of parasite biology and transmission to mosquito vectors.

A randomized clinical trial to compare P. falciparum gametocytaemia and infectivity following blood-stage or mosquito bite induced controlled malaria infection

April 6, 2020 - 15:41 -- Open Access
Alkema M, Reuling IJ, Bousema T, et al.
J Infect Dis. 2020 Apr 2. pii: jiaa157

For malaria elimination efforts it is important to better understand parasite transmission to mosquitoes and develop models for early-clinical evaluation of transmission-blocking interventions.

Blood group and size dependent stability of P. falciparum infected red blood cell aggregates in capillaries

March 25, 2020 - 14:57 -- Open Access
Jötten AM, Moll K, Wahlgren M, Wixforth A, Westerhausen C
Biomicrofluidics, Volume 14, Issue 2

For Plasmodium falciparum related malaria (B50), one of the outstanding host factors for the development of severe disease is the ABO blood group of malaria patients, where blood group O reduces the probability of severe disease as compared to individuals of groups A, B, or AB.

NOT Open Access | Nano-Focused Scanning X-ray Fluorescence Microscopy Reveals an Effect of Hemoglobin S and C on Biochemical Activities in P. falciparum-Infected Erythrocytes

March 24, 2020 - 12:29 -- NOT Open Access
Fröhlich B, Yang Y, Thoma J, Czajor J, Lansche C, Sanchez C, Lanzer M, Cloetens P, Tanaka M
Anal Chem. 2020 Mar 23

Ample evidence suggesting that carriers of hemoglobin S and C are protected from life-threatening malaria, but little is known about the underlying biochemical mechanisms at the single cell level. Using nano-focused scanning X-ray fluorescence microscopy, we quantify the spatial distribution of individual elements in subcellular compartments, including Fe, S, P, Zn, and Cu, in Plasmodium falciparum-infected erythrocytes carrying the wild type or variant hemoglobins.

Not Open Access | The Antimalarial Natural Product Salinipostin A Identifies Essential α/β Serine Hydrolases Involved in Lipid Metabolism in P. falciparum Parasites

February 24, 2020 - 13:40 -- NOT Open Access
Yoo E, Schulze CJ, Stokes BH, Onguka O, Yeo T, Mok S, Gnädig NF, Zhou Y, Kurita K, Foe IT, Terrell SM, Boucher MJ, Cieplak P, Kumpornsin K, Lee MCS, Linington RG, Long JZ, Uhlemann AC, Weerapana E, Fidock DA, Bogyo M
Cell Chem Biol. 2020 Feb 20;27(2):143-157.e5

Salinipostin A (Sal A) is a potent antiplasmodial marine natural product with an undefined mechanism of action. Using a Sal A-derived activity-based probe, we identify its targets in the Plasmodium falciparum parasite. All of the identified proteins contain α/β serine hydrolase domains and several are essential for parasite growth. One of the essential targets displays a high degree of homology to human monoacylglycerol lipase (MAGL) and is able to process lipid esters including a MAGL acylglyceride substrate.

Preclinical Antimalarial Combination Studies: The Case of M5717, a P. falciparum Elongation Factor 2 Inhibitor and Pyronaridine, a Hemozoin Formation Inhibitor

February 17, 2020 - 14:33 -- Open Access
Rottmann M, Jonat B, Spangenberg T, et al.
Antimicrob Agents Chemother. 2020 Feb 10, pii: AAC.02181-19.

Antimalarial drug resistance in the Plasmodium falciparum parasite poses a constant challenge for drug development. To mitigate this risk, new antimalarial medicines should be developed as fixed-dose combinations. Assessing the pharmacodynamic interactions of potential antimalarial drug combination partners during early phases of development is essential in developing the targeted parasitological and clinical profile of the final drug product.


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