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p. falciparum

Blood donor variability is a modulatory factor for P. falciparum invasion phenotyping assays

March 31, 2021 - 14:21 -- Open Access
Thiam LG, Nyarko PB, Kusi KA, Niang M, Aniweh Y, Awandare GA
Sci Rep. 2021 Mar 29;11(1):7129

Human erythrocytes are indispensable for Plasmodium falciparum development. Unlike other eukaryotic cells, there is no existing erythroid cell line capable of supporting long-term P. falciparum in vitro experiments. Consequently, invasion phenotyping experiments rely on erythrocytes of different individuals. However, the contribution of the erythrocytes variation in influencing invasion rates remains unknown, which represents a challenge for conducting large-scale comparative studies.

Crystal structure of P. falciparum Cpn60 bound to ATP reveals an open dynamic conformation before substrate binding

March 17, 2021 - 09:29 -- Open Access
Nguyen B, Ma R, Tang WK, Shi D, Tolia NH
Sci Rep. 2021 Mar 15;11(1):5930

Plasmodium falciparum harbors group 1 and group 2 chaperonin systems to mediate the folding of cellular proteins in different cellular locations. Two distinct group 1 chaperonins operate in the organelles of mitochondria and apicoplasts, while group 2 chaperonins function in the cytosol. No structural information has been reported for any chaperonin from plasmodium.

NOT Open Access | Quinoline carboxamide core moiety-based compounds inhibit P. falciparumfalcipain-2: Design, synthesis and antimalarial efficacy studies

March 2, 2021 - 15:34 -- NOT Open Access
Singh A, Kalamuddin M, Maqbool M, Mohmmed A, Malhotra P, Hoda N
Bioorg Chem. 2021 Mar;108:104514

Targeting Falcipain-2 (FP2) for the development of antimalarials is a promising and established concept in antimalarial drug discovery and development. FP2, a member of papain-family cysteine protease of the malaria parasite Plasmodium falciparum holds an important role in hemoglobin degradation pathway. A new series of quinoline carboxamide-based compounds was designed, synthesized and evaluated for antimalarial activity.

Structural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum

February 25, 2021 - 10:12 -- Open Access
Pholcharee T, Oyen D, Wilson IA, et al.
Nat Commun. 2021 Feb 16;12(1):1063

The most advanced P. falciparum circumsporozoite protein-based malaria vaccine, RTS,S/AS01 (RTS,S), confers partial protection but with antibody titers that wane relatively rapidly, highlighting the need to elicit more potent and durable antibody responses. Here, we elucidate crystal structures, binding affinities and kinetics, and in vivo protection of eight anti-NANP antibodies derived from an RTS,S phase 2a trial and encoded by three different heavy-chain germline genes.

Breakdown in membrane asymmetry regulation leads to monocyte recognition of P. falciparum-infected red blood cells

February 23, 2021 - 12:55 -- Open Access
Fraser M, Jing W, Bröer S, Kurth F, Sander LE, Matuschewski K, Maier AG
PLoS Pathog. 2021 Feb 18;17(2):e1009259

The human malaria parasite Plasmodium falciparum relies on lipids to survive; this makes its lipid metabolism an attractive drug target. The lipid phosphatidylserine (PS) is usually confined to the inner leaflet of the red blood cell membrane (RBC) bilayer; however, some studies suggest that infection with the intracellular parasite results in the presence of this lipid in the RBC membrane outer leaflet, where it could act as a recognition signal to phagocytes. Here, we used fluorescent lipid analogues and probes to investigate the enzymatic reactions responsible for maintaining asymmetry between membrane leaflets, and found that in parasitised RBCs the maintenance of membrane asymmetry was partly disrupted, and PS was increased in the outer leaflet.

NOT Open Access | Distribution and temporal dynamics of P. falciparum chloroquine resistance transporter mutations associated with piperaquine resistance in Northern Cambodia

February 3, 2021 - 15:27 -- NOT Open Access
Shrestha B, Shah Z, Takala-Harrison S, et al.
J Infect Dis. 2021 Feb 2:jiab055

Newly emerged mutations within the Plasmodium falciparum chloroquine resistance transporter (PfCRT) can confer piperaquine resistance in the absence of amplified plasmepsin II (pfpm2). In this study, we estimated the prevalence of co-circulating piperaquine resistance mutations in P. falciparum isolates collected in northern Cambodia from 2009-2017.

NOT Open Access | In-silico profiling and structural insights into the impact of nSNPs in the P. falciparum acetyl-CoA transporter gene to understand the mechanism of drug resistance in malaria

February 3, 2021 - 14:34 -- NOT Open Access
Sardar R, Katyal N, Ahamad S, Jade DD, Ali S, Gupta D
J Biomol Struct Dyn. 2021 Feb;39(2):558-569

The continuous emergence of resistance to the available drugs poses major constraints in the development of effective therapeutics against malaria. Malaria drug resistance has been attributed to be the manifestation of numerous factors. For example, mutations in the parasite transporter protein acetyl-CoA transporter (Pfact) can remarkably affect its uptake affinity for a drug molecule against malaria, and hence enhance its susceptibility to resistance. To identify major contributors to its loss of functionality, we have thoroughly scrutinized eight such recently reported resistant mutants, via in-silico tools in terms of alterations in different properties.

NOT Open Access | Investigation of factors affecting the production of P. falciparum gametocytes in an Indian isolate

February 2, 2021 - 17:11 -- NOT Open Access
Wadi I, Deora N, Nath M, Sinha A
3 Biotech. 2021 Feb;11(2):55

The fundamental requirement of every gametocytocidal drug screening assay is the sufficient numbers of healthy and viable gametocytes. The number of in vitro gametocytes grossly depends on the genetic capacity of parasites to produce gametocytes and on various environmental factors that are not precisely elucidated. In the present study, we tested multiple environmental factors that are reported, hypothesized, or predicted to influence gametocyte numbers.

4-chloro eugenol interacts synergistically with artesunate against drug resistant P. falciparum inducing oxidative stress

February 2, 2021 - 16:22 -- Open Access
Mina PR, Kumar S, Agarwal K, Kumar R, Pal A, Tandon S, Yadav SK, Yadav S, Darokar MP
Biomed Pharmacother. 2021 Jan 29;137:111311

4-chloro eugenol (4CE), a semisynthetic analog of phytomolecule eugenol exhibited potent antiplasmodial activity with IC50 in the range of 1.5–5 μM against sensitive as well as drug resistant strain of P. falciparum. This analog also showed synergy with a clinically used antimalarial drug artesunate and was able to curtail the IC50 of artesunate up to 4–5 folds. Although, 4CE did not show any effect on heme polymerization, the most common drug target in the malaria parasite, it could increase the level of reactive oxygen species (ROS) and reactive nitrogen species (RNS) alone as well as in combination with artesunate.

A nuclear protein, PfMORC confers melatonin dependent synchrony of the human malaria parasite P. falciparum in the asexual stage

January 26, 2021 - 15:12 -- Open Access
Singh MK, Tessarin-Almeida G, Dias BKM, Pereira PS, Costa F, Przyborski JM, Garcia CRS
Sci Rep. 2021 Jan 21;11(1):2057

The host hormone melatonin is known to modulate the asexual cell-cycle of the human malaria parasite Plasmodium falciparum and the kinase PfPK7 is fundamental in the downstream signaling pathways. The nuclear protein PfMORC displays a histidine kinase domain and is involved in parasite cell cycle control. By using a real-time assay, we show a 24 h (h) rhythmic expression of PfMORC at the parasite asexual cycle and the expression is dramatically changed when parasites were treated with 100 nM melatonin for 17 h.


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