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Scientific Articles

Structure-Activity Relationship between Thiol Group-Trapping Ability of Morphinan Compounds with a Michael Acceptor and Anti-Plasmodium falciparum Activities

March 10, 2020 - 16:04 -- Open Access
Author(s): 
Kutsumura N, Koyama Y, Nagase H, et al.
Reference: 
Molecules. 2020 Mar 2;25(5). pii: E1112

7-Benzylidenenaltrexone (BNTX) and most of its derivatives showed in vitro antimalarial activities against chloroquine-resistant and -sensitive Plasmodium falciparum strains (K1 and FCR3, respectively). In addition, the time-dependent changes of the addition reactions of the BNTX derivatives with 1-propanethiol were examined by 1H-NMR experiments to estimate their thiol group-trapping ability.

Human genetics and malaria resistance

March 9, 2020 - 15:13 -- Open Access
Author(s): 
Kariuki SN, Williams TN
Reference: 
Hum Genet. 2020 Mar 4

Malaria has been the pre-eminent cause of early mortality in many parts of the world throughout much of the last five thousand years and, as a result, it is the strongest force for selective pressure on the human genome yet described. Around one third of the variability in the risk of severe and complicated malaria is now explained by additive host genetic effects. Many individual variants have been identified that are associated with malaria protection, but the most important all relate to the structure or function of red blood cells.

Not Open Access | The role of native and introduced birds in transmission of avian malaria in Hawai'i

March 9, 2020 - 15:12 -- NOT Open Access
Author(s): 
McClure KM, Fleischer RC, Kilpatrick AM
Reference: 
Ecology. 2020 Mar 4:e03038

The introduction of non‐native species and reductions in native biodiversity have resulted in substantial changes in vector and host communities globally, but the consequences for pathogen transmission are poorly understood. In lowland Hawaiʻi, bird communities are composed of primarily introduced species, with scattered populations of abundant native species. We examined the influence of avian host community composition—specifically the role of native and introduced species, as well as host diversity, on the prevalence of avian malaria (Plasmodium relictum) in the southern house mosquito (Culex quinquefasciatus).

Does improving appropriate use of malaria medicines change population beliefs in testing and treatment? Evidence from a randomized controlled trial

March 9, 2020 - 15:10 -- Open Access
Author(s): 
Maffioli EM, Mohanan M, Saran I, O'Meara WP
Reference: 
Health Policy Plan. 2020 Mar 4. pii: czaa010

A major puzzle in malaria treatment remains the dual problem of underuse and overuse of malaria medications, which deplete scarce public resources used for subsidies and lead to drug resistance. One explanation is that health behaviour, especially in the context of incomplete information, could be driven by beliefs, pivotal to the success of health interventions. The objective of this study is to investigate how population beliefs change in response to an experimental intervention which was shown to improve access to rapid diagnostic testing (RDT) through community health workers (CHWs) and to increase appropriate use of anti-malaria medications.

NOT Open Access | Molecular target validation of Aspartate Transcarbamoylase from Plasmodium falciparum by Torin 2

March 9, 2020 - 15:08 -- NOT Open Access
Author(s): 
Bosch S, Lunev S, Batista FA, Linzke M, Kronenberger T, Dömling A, Groves MR, Wrenger C
Reference: 
ACS Infect Dis. 2020 Mar 4

Malaria is a tropical disease that kills about half a million people around the world annually. Enzymatic reactions within the pyrimidine biosynthesis have been proven to be essential for Plasmodium proliferation. Here we report on the essentiality of the second enzymatic step of the pyrimidine biosynthesis pathway, catalysed by Aspartate Transcarbamoylase (ATC). Crystallisation experiments using a double mutant PfATC revealed the importance of the mutated residues for enzyme catalysis.

Inactivation of Plasmodium falciparum in whole blood using the amustaline and glutathione pathogen reduction technology

March 9, 2020 - 15:06 -- Open Access
Author(s): 
Sow C, Laughhunn A, Girard YA, Lanteri MC, Amar El Dusouqui S, Stassinopoulos A, Grellier P
Reference: 
Transfusion. 2020 Mar 4

Risk of transfusion‐transmitted (TT) malaria is mainly associated with whole blood (WB) or red blood cell (RBC) transfusion. Risk mitigation relies mostly on donor deferral while a limited number of countries perform blood testing, both negatively impacting blood availability. This study investigated the efficacy of the pathogen reduction system using amustaline and glutathione (GSH) to inactivate Plasmodium falciparum in WB.

Microarray analyses reveal strain-specific antibody responses to Plasmodium falciparum apical membrane antigen 1 variants following natural infection and vaccination

March 9, 2020 - 15:03 -- Open Access
Author(s): 
Bailey JA, Berry AA, Plowe CV, et al.
Reference: 
Sci Rep. 2020 Mar 3;10(1):3952

Vaccines based on Plasmodium falciparum apical membrane antigen 1 (AMA1) have failed due to extensive polymorphism in AMA1. To assess the strain-specificity of antibody responses to malaria infection and AMA1 vaccination, we designed protein and peptide microarrays representing hundreds of unique AMA1 variants. Following clinical malaria episodes, children had short-lived, sequence-independent increases in average whole-protein seroreactivity, as well as strain-specific responses to peptides representing diverse epitopes.

Not Open Access | Plasmodium chaperonin TRiC/CCT identified as a target of the antihistamine clemastine using parallel chemoproteomic strategy

March 9, 2020 - 14:59 -- NOT Open Access
Author(s): 
Lu KY, Quan B, Sylvester K, Srivastava T, Fitzgerald MC, Derbyshire ER
Reference: 
Proc Natl Acad Sci U S A. 2020 Mar 3. pii: 201913525

The antihistamine clemastine inhibits multiple stages of the Plasmodium parasite that causes malaria, but the molecular targets responsible for its parasite inhibition were unknown. Here, we applied parallel chemoproteomic platforms to discover the mechanism of action of clemastine and identify that clemastine binds to the Plasmodium falciparum TCP-1 ring complex or chaperonin containing TCP-1 (TRiC/CCT), an essential heterooligomeric complex required for de novo cytoskeletal protein folding. Clemastine destabilized all eight P. falciparum TRiC subunits based on thermal proteome profiling (TPP).

Mapping the travel patterns of people with malaria in Bangladesh

March 9, 2020 - 14:57 -- Open Access
Author(s): 
Sinha I, Sayeed AA, Maude RJ, et al.
Reference: 
BMC Med. 2020 Mar 4;18(1):45

Spread of malaria and antimalarial resistance through human movement present major threats to current goals to eliminate the disease. Bordering the Greater Mekong Subregion, southeast Bangladesh is a potentially important route of spread to India and beyond, but information on travel patterns in this area are lacking.

NOT Open Access | Heterogeneous Expression of the Ammonium Transporter AgAmt in Chemosensory Appendages of the Malaria Vector, Anopheles gambiae

March 9, 2020 - 14:44 -- NOT Open Access
Author(s): 
Ye Z, Liu F, Sun H, Barker M, Pitts RJ, Zwiebel LJ
Reference: 
Insect Biochemistry and Molecular Biology, 29 February 2020, 103360

Ammonia is one of the principal kairomones originating from human and other animal emanations and in that context, plays an essential role in the host-seeking behaviors of the malaria vector mosquito Anopheles gambiae. Nevertheless, despite its importance in directing host-seeking, the mechanisms underlying ammonia detection in the mosquito olfactory system remains largely unknown.

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