Tutankhamun's Antimalarial Drug for Covid-19.

Drug repositioning is a strategy that identifies new uses of approved drugs to treat conditions different from their original purpose. Current efforts to treat Covid-19 are based on this strategy. The first drugs used in patients infected with SARS-CoV-2 were antimalarial drugs. It is their mechanism of action, i. e., rise in endosomal pH, which recommends them against the new coronavirus. Disregarding their side effects, the study of their antiviral activity provides valuable hints for the choice and design of drugs against SARS-CoV-2. One prominent drug candidate is thymoquinone, an antimalarial substance contained in Nigella sativa - most likely one of the first antimalarial drugs in human history. Since the outbreak of the pandemic, the number of articles relating thymoquinone to Covid-19 continuously increases. Here, we use it as an exemplary model drug, compare its antiviral mechanism with that of conventional antimalarial drugs and establish an irreducible parametric scheme for the identification of drugs with a potential in Covid-19.Translation into the laboratory is simple. Starting with the discovery of Nigella sativa seeds in the tomb of Pharaoh Tutankhamun, we establish a physicochemical model for the interaction of thymoquinone with both coronavirus and cells. Exploiting the predictive capability of the model, we provide a generalizable scheme for the systematic choice and design of drugs for Covid-19. An unexpected offshoot of our research is that Tutankhamun could not have died of malaria, a finding contrary to the mainstream theory.

Tu Youyou winning the Nobel Prize: Ethical research on the value and safety of traditional Chinese medicine.

In 2015, the Chinese pharmacologist, Tu Youyou, was awarded the Nobel Prize for Physiology or Medicine for the discovery of artemisinin. Traditional Chinese medicine (TCM) was the source of inspiration for Tu's discovery and provides an opportunity for the world to know more about TCM as a source of medical knowledge and practice. In this article, the value of TCM is evaluated from an ethical perspective. The characteristics of 'jian, bian, yan, lian' are explored in the way they promote accessibility and economic efficiency for TCM. The article also examines how the increased use and prevalence of TCM reflects the scientific, cultural, and ethical values of TCM and their increasing attraction in meeting major challenges to medicine and health systems currently and in the future. The article discusses safety issues within TCM, which is a controversial area, and also comments on some shortcomings and challenges which pose difficulties for more widespread and greater uptake of TCM-derived clinical or therapeutic interventions. The article concludes that TCM is generally safe if it is used according to TCM theory and where such applications are cognizant of the strengths and weaknesses of TCM. TCM has important bioethical values which may inform potential measures for meeting challenges facing global health care systems and the article argues that it can have an increasing role in improving human health.

El nacimiento de la especialidad farmacéutica / Birth of the pharmaceutical specialty

No disponible

Two successful decades of Swiss collaborations to develop new anti-malarials.

Over the last two decades there has been a renaissance in the pipeline of new drugs targeting malaria, with the launch of new products that help save the lives of children throughout the world. In addition, there is a wealth of new molecules both entering and progressing through clinical development. These bring hope for a new generation of simpler and more effective cures that could overcome the emerging threat of drug resistance. In addition, there is hope that some of these medicines will have prophylactic activity and can be used to protect vulnerable populations, given the absence of a highly effective vaccine. Switzerland has played a key role in the development of these medicines. First, the country has a long history of understanding the biology of parasites and the pharmacology of drug responses through the leadership of the Swiss Tropical and Public Health Institute in Basel. Second, the highly successful Swiss pharmaceutical industry brings, beyond excellence, a strong interest in neglected diseases, building on work at Hoffmann-La Roche in the last century and with more recent products from Novartis and other Swiss companies. Third, the emergence of product-development-partnerships, in this case led by the Medicines for Malaria Venture, based in Geneva, has helped to catalyze the development of new medicines and bring the community together within Switzerland and beyond. Finally, this progress would not have been possible without the engagement of the Swiss people and the support of the federal government through the Swiss Agency for Development and Cooperation (SDC), the State Secretariat of Education, Research and Innovation (SERI) and the Swiss Republic and Canton of Geneva.

Artemisinin and Chinese Medicine as Tu Science.

The story of discovery of artemisinin highlights the diversity of scientific values across time and space. Resituating artemisinin research within a broader temporal framework allows us to understand how Chinese drugs like qinghao came to articulate a space for scientific experimentation and innovation through its embodiment of alternating clusters of meanings associated with tu and yang within scientific discourse. Tu science, which was associated with terms like native, Chinese, local, rustic, mass, and crude, articulated a radical vision of science in the service of socialist revolutionary ideals. Yang science, which signified foreign, Western, elite, and professional, tended to bear the hallmarks of professionalism, transnational networks in education and training, and an emphasis on basic or foundational research. With respect to medical research, the case of artemisinin highlights how the constitution of socialist science as an interplay of tu and yang engendered different scientific values and parameters for scientific endeavor. Modern medical research in Maoist China could harness the productive energies of mass participation to technical expertise in its investigations of Chinese drugs, and under the banner of tu science, it became possible and scientifically legitimate to research Chinese drugs in ways that had previously provoked resistance and controversy.

Perspectiva histórica de antimaláricos de origen natural / Historical perspective of antimalarials of natural origin

Hoy, muchas enfermedades son tratadas gracias al descubrimiento de compuestos a partir de las plantas, lo que evidencia que estas juegan un papel significativo en el descubrimiento y desarrollo de nuevos fármacos. Una de las alternativas para el control de la morbi-mortalidad por malaria es la quimioterapia, la cual ha sido posible gracias al descubrimiento de compuestos a partir de las plantas. En la actualidad, cerca de la mitad de los fármacos antimaláricos disponibles son compuestos naturales o están relacionados con ellos. En esta revisión se hace un recuento histórico del origen y desarrollo de los principales antimaláricos como instrumento de hechos arquitectónicos, que mantienen una estrecha relación con los referentes antimaláricos, que sirven de modelos para profundizar en la búsqueda de nuevas sustancias químicas naturales que podrían contribuir al control de una devastadora enfermedad como la malaria, donde se están presentando cepas resistentes de Plasmodium a los principales tratamientos, falla terapéutica, además de un escaso acceso a los medicamentos, entre otros factores; que complican su prevención y tratamiento (AU)

Today, many diseases are treated thanks to the discovery of compounds from plants, which shows that they play a significant role in the discovery and development of new drugs. One of the alternatives for the control of malaria morbidity and mortality is chemotherapy, which has been made possible by the discovery of compounds from plants. At present, about half of the available antimalarials drugs are naturally occurring compounds or are related to them. This review provides a historical account of the origin and development of the main antimalarials as an instrument of architectural facts, which maintains a close relationship with the antimalarials referents, which serve as models to deepen the search for new natural chemical substances that could contribute to the Control of a devastating disease like malaria, where resistant strains of Plasmodium are being presented to the main treatments, therapeutic failure, in addition to poor access to medicines, among other factors; which complicate their prevention and treatment (AU)

Synthetic Strategies for Peroxide Ring Construction in Artemisinin.

The present review summarizes publications on the artemisinin peroxide fragment synthesis from 1983 to 2016. The data are classified according to the structures of a precursor used in the key peroxidation step of artemisinin peroxide cycle synthesis. The first part of the review comprises the construction of artemisinin peroxide fragment in total syntheses, in which peroxide artemisinin ring resulted from reactions of unsaturated keto derivatives with singlet oxygen or ozone. In the second part, the methods of artemisinin synthesis based on transformations of dihydroartemisinic acid are highlighted.

The Hidden History of a Famous Drug: Tracing the Medical and Public Acculturation of Peruvian Bark in Early Modern Western Europe (c. 1650-1720).

The history of the introduction of exotic therapeutic drugs in early modern Europe is usually rife with legend and obscurity and Peruvian bark is a case in point. The famous antimalarial drug entered the European medical market around 1640, yet it took decades before the bark was firmly established in pharmaceutical practice. This article argues that the history of Peruvian bark can only be understood as the interplay of its trajectories in science, commerce, and society. Modern research has mostly focused on the first of these, largely due to the abundance of medico-historical data. While appreciating these findings, this article proposes to integrate the medical trajectory in a richer narrative, by drawing particular attention to the acculturation of the bark in commerce and society. Although the evidence we have for these two trajectories is still sketchy and disproportionate, it can nevertheless help us to make sense of sources that have not yet been an obvious focus of research. Starting from an apparently isolated occurrence of the drug in a letter, this article focuses on Paris as the location where medical and public appreciation of the bark took shape, by exploring several contexts of knowledge circulation and medical practice there. These contexts provide a new window on the early circulation of knowledge of the bark, at a time when its eventual acceptance was by no means certain.

Quinine, Malaria, and the Cinchona Bureau: Marketing Practices and Knowledge Circulation in a Dutch Transoceanic Cinchona-Quinine Enterprise (1920s-30s).

In this study, we will show how a Dutch pharmaceutical consortium of cinchona producers and quinine manufacturers was able to capitalize on one of the first international public health campaigns to fight malaria, thereby promoting the sale of quinine, an antimalarial medicine. During the 1920s and 1930s, the international markets for quinine were controlled by this Dutch consortium, which was a transoceanic cinchona-quinine enterprise centered in the Cinchona Bureau in the Netherlands. We will argue that during the interwar period, the Cinchona Bureau became the decision-making center of this Dutch cinchona-quinine pharmaceutical enterprise and monopolized the production and trade of an essential medicine. In addition, we will argue that capitalizing on the international public health campaign in the fight against malaria by the Dutch cinchona-quinine enterprise via the Cinchona Bureau can be regarded as an early example of corporate colonization of public health by a private pharmaceutical consortium. Furthermore, we will show how commercial interests prevailed over scientific interests within the Dutch cinchona-quinine consortium, thus interfering with and ultimately curtailing the transoceanic circulation of knowledge in the Dutch empire.

Le laboratoire et le bled. L'Institut Pasteur d'Alger et les médecins de colonisation dans la lutte contre le paludisme (1904-1939) / The laboratory and the village. The Algiers Pasteur Institute and «colonization physicians» in the fight against malaria (1904-1939)

Dès la fin du XIXe siècle, plusieurs médecins installés en Algérie ainsi que les professeurs de l'Ecole supérieure de médecine d'Alger cherchent à cartographier le paludisme pour tenter de proposer la prophylaxie de la maladie, fréquente dans les campagnes de la colonie. Lorsque la lutte contre le paludisme s'organise en Algérie au début du XXe siècle sous l'égide du gouvernement général et de l'Institut Pasteur, les médecins de cet établissement ont besoin de données diverses pour établir des index endémiques et organiser des programmes d'action. Déjà relais de l'administration dans les campagnes algériennes, les médecins de colonisation, personnel chargé des soins médicaux des populations des districts ruraux depuis les années 1850, apparaissent dans les campagnes comme des collaborateurs tout trouvés d'une organisation qui fonctionne également avec des agents quininisateurs, des agents s'occupant des mesures antilarvaires mais aussi d'autres services de la colonie comme les Ponts et chaussées et le service hydraulique. On insiste cependant régulièrement sur la nécessité de les former aux nouvelles techniques de parasitologie. Des cours de perfectionnement sont ainsi proposés pour faire de ces praticiens des relais aussi efficaces que possibles du service antipaludique. C'est notamment l'ambition du cours de 34 jours organisé à partir de 1932 par l'Institut Pasteur d'Algérie (AU)

From the late 19th century, some of the physicians settled in Algeria and teachers at the School of Medicine of Algiers sought to map the extent of malaria in order to propose prophylactic measures against a disease that was widespread in the countryside of the colony. When the fight against malaria was organized in Algeria at the beginning of the 20th century, under the joint direction of the General Government and the Pasteur Institute, the Institute researchers needed to gather various types of data for determining epidemic indexes and preparing action programmes. The so-called «colonization physicians», responsible for delivering healthcare to colonials and natives in rural districts since the 1850s, appeared to be appropriate collaborators with the administration in the campaigns. The organizers of these campaigns also worked with agents quininisateurs (quinine distributors) and those involved in anti-larval measures, as well as with agencies responsible for roads and bridges and for water services, among others. However, there were soon repeated calls for them to be trained in the new bacteriology techniques. Advanced courses were also proposed to allow these practitioners to act as true and effective agents of the anti-malarial service, such as the 34-day course organized in 1932 by the Pasteur Institute of Algeria (AU)

Cooperative development of antimicrobials: looking back to look ahead.

As foundations and governments mobilize to tackle antimicrobial resistance (AMR), several experiments in academic-industrial collaboration have emerged. Here, I examine two historical precedents, the Penicillin Project and the Malaria Project of the Second World War, and two contemporary examples, the Tuberculosis Drug Accelerator programme and the Tres Cantos Open Lab. These and related experiments suggest that different strategies can be effective in managing academic-industrial collaborations, and that such joint projects can prosper in both multisite and single-site forms, depending on the specific challenges and goals of each project. The success of these strategies and the crisis of AMR warrant additional investment in similar projects.

Fighting fire with fire: mass antimalarial drug administrations in an era of antimalarial resistance.

The emergence and spread of antimalarial resistance has been a major liability for malaria control. The spread of chloroquine-resistant Plasmodium falciparum strains had catastrophic consequences for people in malaria-endemic regions, particularly in sub-Saharan Africa. The recent emergence of artemisinin-resistant P. falciparum strains is of highest concern. Current efforts to contain artemisinin resistance have yet to show success. In the absence of more promising plans, it has been suggested to eliminate falciparum malaria from foci of artemisinin resistance using a multipronged approach, including mass drug administrations. The use of mass drug administrations is controversial as it increases drug pressure. Based on current knowledge it is difficult to conceptualize how targeted malaria elimination could contribute to artemisinin resistance, provided a full treatment course is ensured.