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Scientific Articles

Not Open Access | An apicoplast-resident folate transporter is essential for sporogony of malaria parasites

September 29, 2020 - 12:59 -- NOT Open Access
Korbmacher F, Drepper B, Sanderson T, Martin P, Stach T, Maier AG, Matuschewski K, Matz JM
Cell Microbiol. 2020 Sep 25:e13266

Malaria parasites are fast replicating unicellular organisms and require substantial amounts of folate for DNA synthesis. Despite the central role of this critical co-factor for parasite survival, only little is known about intraparasitic folate trafficking in Plasmodium.

Antibody responses to a suite of novel serological markers for malaria surveillance demonstrate strong correlation with clinical and parasitological infection across seasons and transmission settings in The Gambia

September 29, 2020 - 12:57 -- Open Access
Wu L, Mwesigwa J, Affara M, Bah M, Correa S, Hall T, Singh SK, Beeson JG, Tetteh KKA, Kleinschmidt I, D'Alessandro U, Drakeley C
BMC Med. 2020 Sep 25;18(1):304

As malaria transmission declines, sensitive diagnostics are needed to evaluate interventions and monitor transmission. Serological assays measuring malaria antibody responses offer a cost-effective detection method to supplement existing surveillance tools.

NOT Open Access | Functionally engineered 'hepato-liposomes': Combating liver-stage malaria in a single prophylactic dose

September 29, 2020 - 12:55 -- NOT Open Access
Marwah M, Narain Srivastava P, Mishra S, Nagarsenker M
Int J Pharm. 2020 Sep 25;587:119710

Primaquine continues to remain the gold standard molecule with an incumbent toxicity profile, as far as radical treatment of malaria is concerned. Better molecules are available at experimental level but their targeted delivery is a challenge. The present work identifies 'Decoquinate (DQN)' as a repurposed, safer drug molecule with a potential to function as an appealing replacement for primaquine active against liver-stage malaria.

Pharmacological and cardiovascular perspectives on the treatment of COVID-19 with chloroquine derivatives

September 24, 2020 - 14:05 -- Open Access
Zhang XL, Li ZM, Ye JT, Lu J, Ye LL, Zhang CX, Liu PQ, Duan DD
Acta Pharmacol Sin. 2020 Sep 23

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and an ongoing severe pandemic. Curative drugs specific for COVID-19 are currently lacking. Chloroquine phosphate and its derivative hydroxychloroquine, which have been used in the treatment and prevention of malaria and autoimmune diseases for decades, were found to inhibit SARS-CoV-2 infection with high potency in vitro and have shown clinical and virologic benefits in COVID-19 patients.

Genetic screens reveal a central role for heme metabolism in artemisinin susceptibility

September 24, 2020 - 14:02 -- Open Access
Harding CR, Sidik SM, Petrova B, Gnädig NF, Okombo J, Herneisen AL, Ward KE, Markus BM, Boydston EA, Fidock DA, Lourido S
Nat Commun. 2020 Sep 23;11(1):4813.

Artemisinins have revolutionized the treatment of Plasmodium falciparum malaria; however, resistance threatens to undermine global control efforts. To broadly explore artemisinin susceptibility in apicomplexan parasites, we employ genome-scale CRISPR screens recently developed for Toxoplasma gondii to discover sensitizing and desensitizing mutations.

Dispensable Role of Mitochondrial Fission Protein 1 (Fis1) in the Erythrocytic Development of Plasmodium falciparum

September 24, 2020 - 14:01 -- Open Access
Maruthi M, Ling L, Zhou J, Ke H
mSphere. 2020 Sep 23;5(5):e00579-20

Malaria remains a huge global health burden, and control of this disease has run into a severe bottleneck. To defeat malaria and reach the goal of eradication, a deep understanding of the parasite biology is urgently needed. The mitochondrion of the malaria parasite is essential throughout the parasite's life cycle and has been validated as a clinical drug target. In the asexual development of Plasmodium spp., the single mitochondrion grows from a small tubular structure to a complex branched network.

NOT Open Access | Gene editing reveals obligate and modulatory components of the CO(2) receptor complex in the malaria vector mosquito, Anopheles coluzzii

September 24, 2020 - 08:17 -- NOT Open Access
Liu F, Ye Z, Baker A, Sun H, Zwiebel LJ
Insect Biochem Mol Biol. 2020 Sep 20:103470

The sensitivity to volatile carbon dioxide (CO2) produced by humans and other animals is a critical component in the host preference behaviors of the malaria vector mosquito Anopheles coluzzii. The molecular receptors responsible for the ability to sense CO2 are encoded by three putative gustatory receptor (Gr) genes (Gr22,23,24) which are expressed in a distinctive array of sensory neurons housed in maxillary palp capitate peg sensilla of An. coluzzii.

Bisphosphoglycerate Mutase Deficiency Protects against Cerebral Malaria and Severe Malaria-Induced Anemia

September 24, 2020 - 08:15 -- Open Access
Xu G, van Bruggen R, Gros P, et al.
Cell Rep. 2020 Sep 22;32(12):108170

The replication cycle and pathogenesis of the Plasmodium malarial parasite involves rapid expansion in red blood cells (RBCs), and variants of certain RBC-specific proteins protect against malaria in humans. In RBCs, bisphosphoglycerate mutase (BPGM) acts as a key allosteric regulator of hemoglobin/oxyhemoglobin. We demonstrate here that a loss-of-function mutation in the murine Bpgm (BpgmL166P) gene confers protection against both Plasmodium-induced cerebral malaria and blood-stage malaria.

NOT Open Access | The malaria metabolite HMBPP does not trigger erythrocyte terpene release

September 24, 2020 - 08:13 -- NOT Open Access
Miller JJ, Odom John A
ACS Infect Dis. 2020 Sep 23

Infection with malarial parasites renders hosts more mosquito attractive than their uninfected, healthy, counterparts. One volatile organic compound, α-pinene, is associated with <I>Plasmodium</i> spp. infection in multiple studies and is a known mosquito attractant.

NOT Open Access | Structural Basis for Inhibitor Potency and Selectivity of Plasmodium falciparum Phosphatidylinositol 4-kinase Inhibitors

September 24, 2020 - 08:11 -- NOT Open Access
Fienberg S, Eyermann CJ, Arendse L, Basarab GS, McPhail J, Burke JE, Chibale K
ACS Infect Dis. 2020 Sep 23

Plasmodium falciparum phosphatidylinositol 4-kinase (PfPI4K) has emerged as a promising new drug target for novel antimalarial therapeutics. In the absence of a reliable high-resolution three-dimensional structure, a homology model of PfPI4K was built as a tool for structure-based drug design.


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