2015 Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine 2015 was awarded to William C. Campbell, Satoshi Ōmura and Youyou Tu.
William Campbell and Satoshi Ōmura shared one-half of the prize for their discoveries of a new drug, Avermectin, that was highly effective against a spectrum of parasitic worm infections. The derivatives of this compound are currently being used to eradicate and prevent the transmission of River Blindness and Lymphatic Filariasis.
Youyou Tu was awarded the other half of the Nobel Prize for her discovery of Artemisinin, a drug that has become a frontline treatment for malaria and has significantly reduced the mortality rates for patients suffering from this disease worldwide.
In celebration, NPG is making available a range of articles from its journal archives that feature these scientists’ remarkable achievements and highlight recent progress in these fields.
Image Credit: EYE OF SCIENCE/SCIENCE PHOTO LIBRARY
News and Comments
Entry of the antimalarial drug precursor semi-synthetic artemisinin into industrial production is the first major milestone for the application of synthetic biology. In this Review, Paddon and Keasling discuss the metabolic engineering and synthetic biology approaches that were used to engineer Escherichia coli and Saccharomyces cerevisiae to synthesize a precursor of artemisinin, which should aid the development of other pharmaceutical products.
Long ignored by pharmaceutical companies and global health agencies alike, 'neglected tropical diseases' devastate people in the poorest parts of the world. But they're finally getting the attention they deserve, reports Apoorva Mandavilli.
In this Science and Society article, Carl Nathan reviews historical collaborations between industry and academic instiutions that developed antimicrobials, and discusses similar strategies that have recently emerged to tackle the crisis of antimicrobial resistance.
The screening of natural products for lead molecules is an attractive strategy, as most natural products fall within biologically relevant chemical space. In this Review, Harvey, Edrada-Ebel and Quinn discuss how advanced screening, metabolomics and metagenomics approaches can be used in the identification, validation and production of naturally sourced compounds, and highlight examples of naturally derived antimicrobials and inhibitors of protein–protein interactions.
Reviews and Research
Two semi-synthetic processes for the production of the antimalarial natural product artemisinin have been developed by applying the principles of green chemistry. Solvent manipulation allows catalyst recycling and reduction of waste, ultimately leading to a purification-free process with lower environmental and economic costs; a potential contribution to the world-wide fight against malaria.
In this study, the authors present an analysis of the malaria burden in sub-Saharan Africa between 2000 and 2015, and quantify the effects of the interventions that have been implemented to combat the disease; they find that the prevalence of Plasmodium falciparum infection has been reduced by 50% since 2000 and the incidence of clinical disease by 40%, and that interventions have averted approximately 663 million clinical cases since 2000, with insecticide-treated bed nets being the largest contributor.
The description of a compound (DDD107498) with antimalarial activity against multiple life-cycle stages of Plasmodium falciparum and good pharmacokinetic and safety properties, with potential for single-dose treatment, chemoprotection and prevention of transmission.
Saccharomyces cerevisiae is engineered to produce high concentrations of artemisinic acid, a precursor of the artemisinin used in combination therapies for malaria treatment; an efficient and practical chemical process to convert artemisinic acid to artemisinin is also developed.
Dominic Kwiatkowski and colleagues report a large multicenter genome-wide association study of Plasmodium falciparum resistance to artemisinin. They identify markers of a genetic background on which kelch13 mutations conferring artemisinin resistance are likely to emerge.
The nuclear Farnesoid X receptor (FXR) regulates bile acid and cholesterol production. Here Jin et al. identify the clinically approved antiparasitic drug ivermectin as a novel FXR ligand and show that it has antidiabetic effects in mice.
Editing the genome of a malarial parasite with Cas9 validates a drug-resistance polymorphism
Single guide RNAs driven by a T7 promoter target Cas9 to two endogenous loci, leading to fast and efficient genome editing in the malaria parasite P. falciparum.
New X-ray crystal structure and immunoanalyses of alanyl aminopeptidase N (AnAPN1), a gut antigen of the Anopheles mosquito vector of Plasmodium falciparum, reveal how AnAPN1-specific antibodies block transmission of the malarial parasite.
Artemisinins are key anti-malarial drugs, but artemisinin resistance has been increasing; this study identifies the molecular target of artemisinins as phosphatidylinositol-3-kinase and increase of the lipid product phosphatidylinositol-3-phosphate induces resistance in Plasmodium falciparum.
Screening for new anthelmintic compounds that are active against parasitic nematodes is costly and labour intensive. Here, the authors use the non-parasitic nematode Caenorhabditis elegans to identify 30 anthelmintic lead compounds in an effective and cost-efficient manner.