New Strides in Prevention of Malaria during Pregnancy Present Multitudinous Opportunities.

Pregnant women are at a higher risk of developing complications from malaria, a mosquito-borne disease caused by parasites, resulting in considerable maternal and infant morbidity and mortality. Malaria in pregnancy causes unfavorable and life-threatening outcomes for both the mother and fetus not limited to maternal anemia, hypoglycaemia, cerebral malaria, pulmonary edema, and puerperal sepsis. WHO recommends wide-ranging strategies for this detrimental but preventable disease; however, numerous challenges persist in ensuring high uptake of preventive therapies, effective usage of insecticide-treated bed nets, and early initiation and optimal antenatal care coverage for pregnant women.

Profiles of global mutations in the human intercellular adhesion molecule-1 (ICAM-1) shed light on population-specific malaria susceptibility.

Plasmodium falciparum is responsible for malaria-related morbidity and mortality. PfEMP1 (P. falciparum erythrocyte membrane protein 1) mediates infected erythrocytes adhesion to various surface vascular receptors, including intercellular adhesion molecule-1 (ICAM-1), associating this interaction with severe malaria in several studies.

Socioecological risk factors associated with Malaria in Pregnancy in an endemic state of India: a retrospective study.

Introduction: Malaria in Pregnancy (MiP) has significant adverse effects on both mother and fetus. Pregnant women in regions with unstable malaria transmission are three times more vulnerable to infection. This study analysed malaria prevalence among pregnant women in Odisha, India from 2016 to 2020 and compared it with overall malaria rates.

Structural and genomic analysis of single nucleotide polymorphisms in human host factor endothelial protein C receptor (EPCR) reveals complex interplay with malaria parasites.

Plasmodium parasites responsible for malaria follow a complex life cycle of which half takes place inside the human host. Parasites present diverse antigens at different stages of their life cycle and interact with many surface molecules to attach to and enter host cells. The CIDRα1 domain of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) in infected erythrocytes adheres to one such vascular receptor endothelial protein C receptor (EPCR).

Single-Nucleotide Polymorphisms in Glucose-6-Phosphate Dehydrogenase and their Relevance for the Deployment of Primaquine as a Radical Cure for Malaria.

Malaria remains an important public health problem despite efforts to control it. Besides active transmission, relapsing malaria caused by dormant liver stages of Plasmodium vivax and Plasmodium ovale hypnozoites is a major hurdle in malaria control and elimination programs. Primaquine (PQ) is the most widely used drug for radical cure of malaria.

Exploration of aminoacyl-tRNA synthetases from eukaryotic parasites for drug development.

Parasitic diseases result in considerable human morbidity and mortality. The continuous emergence and spread of new drug-resistant parasite strains is an obstacle to controlling and eliminating many parasitic diseases. Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous enzymes essential for protein synthesis.

Structural Profiles of SARS-CoV-2 Variants in India.

India was severely affected by several waves of SARS-CoV-2 infection that occurred during April-June 2021 (second wave) and December 2021-January 2022 (third wave) and thereafter, resulting in >10 million new infections and a significant number of deaths. Global Initiative on Sharing Avian Influenza Data database was used to collect the sequence information of ~10,000 SARS-CoV-2 patients from India and our sequence analysis identified three variants B.1.

Genomic analysis of single nucleotide polymorphisms in malaria parasite drug targets.

Malaria is a life-threatening parasitic disease caused by members of the genus Plasmodium. The development and spread of drug-resistant strains of Plasmodium parasites represent a major challenge to malaria control and elimination programmes. Evaluating genetic polymorphism in a drug target improves our understanding of drug resistance and facilitates drug design.

Prospects of halofuginone as an antiprotozoal drug scaffold.

Halofuginone is a clinically active derivative of febrifugine that was first isolated from the Chinese herb Dichroa febrifuga. The beneficial biological effects of halofuginone on various diseases including parasitic diseases, cancer, fibrosis, and autoimmune disorders have been investigated. Halofuginone has reduced toxic side effects when compared to febrifugine, an advantage that has led to the commercial availability of halofuginone-based antiparasitic drugs for animal use, and to human clinical trials for the treatment of tumors and fibrosis.

Structural comparisons reveal diverse binding modes between nucleosome assembly proteins and histones.

Nucleosome assembly proteins (NAPs) are histone chaperones that play a central role in facilitating chromatin assembly/disassembly which is of fundamental importance for DNA replication, gene expression regulation, and progression through the cell cycle. In vitro, NAPs bind to the core histones H2A, H2B, H3, H4 and possibly to H1. The NAP family contains well-characterized and dedicated histone chaperone domain called the NAP domain, and the NAP-histone interactions are key to deciphering chromatin assembly.

Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine.

Placental malaria is a public health burden particularly in Africa as it causes severe symptoms and results in stillbirths or maternal deaths. Plasmodium falciparum protein VAR2CSA drives placental malaria (PM) in pregnant women by adhering to chondroitin sulfate A (CSA) on the placenta. VAR2CSA is a primary vaccine candidate for PM with two vaccines based on it already under clinical trials.

Antigen exposure leads to rigidification of germline antibody combining site.

Immune complexes involving diverse antigens and corresponding antibodies were analyzed for mapping conformational transitions of an antibody before antigen binding, upon antigen binding and after antigen release. Molecular dynamics simulations of the two comprehensive datasets consisting of the antigen-free and antigen-bound structures of the germline antibodies 36-65 and BBE6.12H3 provided mechanistic model of antigen encounter by primary antibodies.

Structure, localization and histone binding properties of nuclear-associated nucleosome assembly protein from Plasmodium falciparum.

Background: Nucleosome assembly proteins (NAPs) are histone chaperones that are crucial for the shuttling and incorporation of histones into nucleosomes. NAPs participate in the assembly and disassembly of nucleosomes thus contributing to chromatin structure organization. The human malaria parasite Plasmodium falciparum contains two nucleosome assembly proteins termed PfNapL and PfNapS.

Iodide-SAD, SIR and SIRAS phasing for structure solution of a nucleosome assembly protein.

The crystal structure of Plasmodium falciparum nucleosome assembly protein (PfNapL) was determined by iodide-SAD/SIRAS phasing methods using iodide-SAD data to 3.0 A resolution and native data to 2.4 A resolution.

Structural insights into chondroitin sulphate A binding Duffy-binding-like domains from Plasmodium falciparum: implications for intervention strategies against placental malaria.

Background: Placental malaria is typified by selective clustering of Plasmodium falciparum in the intervillous blood spaces of the placenta. Sequestration of malaria parasite in the human placenta is mediated by interactions between chondroitin sulphate A (CSA) on the syncytiotrophoblasts and proteins expressed on the surface of infected human erythrocytes. Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) encoded by the var2CSA gene is believed to be the main parasite ligand for CSA-mediated placental binding.

Crystal structure of malaria parasite nucleosome assembly protein: distinct modes of protein localization and histone recognition.

Nucleosome assembly proteins (NAPs) are histone chaperones that are essential for the transfer and incorporation of histones into nucleosomes. NAPs participate in assembly and disassembly of nucleosomes and in chromatin structure organization. Human malaria parasite Plasmodium falciparum contains two nucleosome assembly proteins termed PfNapL and PfNapS.

Structure of a superoxide dismutase and implications for copper-ion chelation.

Superoxide dismutase (SOD) plays a central role in cellular defence against oxidative stress and is of pharmaceutical importance. The SOD from Potentilla atrosanguinea (Pa-SOD) is a unique enzyme as it possesses free-radical scavenging capability at temperatures ranging between 263 and 353 K. The crystal structure of recombinant Pa-SOD has been determined to 2.

Crystal structure of soluble domain of malaria sporozoite protein UIS3 in complex with lipid.

Malaria parasite UIS3 (up-regulated in infective sporozoites gene 3) is essential for sporozoite development in infected hepatocytes. UIS3 encodes for a membrane protein that is localized to the parasite parasitophorous vacuolar membrane in infected hepatocytes. We describe here 2.

SAD phasing of a structure based on cocrystallized iodides using an in-house Cu Kalpha X-ray source: effects of data redundancy and completeness on structure solution.

Superoxide dismutase (SOD) from Potentilla atrosanguinea (Wall. ex. Lehm.