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.

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)

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.

A Brief History of Qinghaosu.

The 2015 Nobel Prize for Medicine or Physiology was awarded to William C. Campbell and Satoshi Omura for their discovery of avermectins, and to Tu You You for her contribution to the discovery of artemisinin. The discovery and development of qinghaosu (artemisinin) as an antimalarial drug is a remarkable and convoluted tale.

Science in the service of colonial agro-industrialism: the case of cinchona cultivation in the Dutch and British East Indies, 1852-1900.

The isolation of quinine from cinchona bark in 1820 opened new possibilities for the mass-production and consumption of a popular medicine that was suitable for the treatment of intermittent (malarial) fevers and other diseases. As the 19th century European empires expanded in Africa and Asia, control of tropical diseases such as malaria was seen as crucial. Consequently, quinine and cinchona became a pivotal tool of British, French, German and Dutch empire-builders. This comparative study shows how the interplay between science, industry and government resulted in different historical trajectories for cinchona and quinine in the Dutch and British Empires during the second half of the 19th century. We argue that in the Dutch case the vectors of assemblage that provided the institutional and physical framework for communication, exchange and control represent an early example of commodification of colonial science. Furthermore, both historical trajectories show how the employment of the laboratory as a new device materialised within the colonial context of agricultural and industrial production of raw materials (cinchona bark), semi-finished product (quinine sulphate) and plant-based medicines like quinine. Hence, illustrating the 19th century transition from 'colonial botany' and 'green imperialism' to what we conceptualise as 'colonial agro-industrialism'.

An Empire's Extract: Chemical Manipulations of Cinchona Bark in the Eighteenth-Century Spanish Atlantic World.

In 1790, the Spanish Crown sent a "botanist-chemist" to South America to implement production of a chemical extract made from cinchona bark, a botanical medicament from the Andes used throughout the Atlantic World to treat malarial fevers. Even though the botanist-chemist's efforts to produce the extract failed, this episode offers important insight into the role of chemistry in the early modern Atlantic World. Well before the Spanish Crown tried to make it a tool of empire, chemistry provided a vital set of techniques that circulated among a variety of healers, who used such techniques to make botanical medicaments useful and intelligible in new ways.

The history of the Greek Anti-Malaria League and the influence of the Italian School of Malariology.

In 1905, a group of eminent Greek physicians led by Professor of Hygiene and Microbiology Constantinos Savvas and the pediatrician Dr. Ioannis Kardamatis founded the Greek Anti-Malaria League. The League assumed a role that the State would not, and for the next 25 years organized the country's anti-malaria campaign. During its first steps, the Greek Anti-Malaria League adopted the principles of Professor Angelo Celli's Italian Anti-Malaria League. The League's accomplishments include a decrease in malarial prevalence, due to mass treatment with quinine, new legislation ensuring the provision of quinine, State monopoly and the collection of epidemiologic data. However, defeat in the Greek-Turkish War (1922) and the massive influx of one million Greek refugees that ensued, led to a change in malarial epidemiology. In 1928, following a visit to Italy, the Greek League adopted the organization and knowledge of the Italian Malaria Schools in Rome and in Nettuno, and this experience served as the basis of their proposal to the State for the development of the anti-malaria services infrastructure. The State adopted many of Professor Savvas' proposals and modified his plan according to Greek needs. The League's experience, accumulated during its 25 years of struggle against malaria, was its legacy to the campaigns that eventually accomplished the eradication of malaria from Greece after World War II.

El Premio Lasker, la Medicina tradicional china y el descubrimiento de la Artemisina / No disponible

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From bark to weed: the history of artemisinin.

In the 1970's, in China, some brilliant and courageous scientists carried out a research programme, which lead to the discovery of artemisinin derivatives and new quinoleines that are used today, in combination, as first line treatment of malaria.

Malaria in the Renaissance: remedies from European herbals from the 16th and 17th century.

BACKGROUND: From antiquity up into the 20th century tertian and quartan malaria which are caused by the parasites Plasmodium vivax and Plasmodium malariae were widespread in Central Europe. Hundreds of different remedies against malaria can be found in herbals from the Renaissance. AIM OF THE STUDY: To document and discuss from a modern pharmacological viewpoint the old remedies described in eight 16th and 17th century herbals written in German. MATERIALS AND METHODS: Eight of the most important herbals of the 16th and 17th century including Bock (1577), Fuchs (1543), Matthiolus (1590), Lonicerus (1560), Brunfels (1532), Zwinger (1696), and Tabernaemontanus (1591 and 1678) were searched for terms related to malaria, and documented plants and recipes described for its treatment. Additionally the overlapping of these remedies with those in De Materia Medica by the Greek physician Dioscorides was studied. RESULTS: Three hundred and fourteen taxa were identified in the herbals for this indication. Recent pharmacological data was found for just 5% of them. The influence of De Materia Medica was shown to be negligible with only 3.5% of the remedies in common. CONCLUSIONS: European Renaissance herbals may be a valuable source of information for the selection of plants for focussed antiplasmodial screening programmes, but have received only little scientific attention. Antimalarial remedies from these herbals must be viewed as independent sources of knowledge separate from Dioscorides' De Materia Medica.

Carolus Linnaeus, the ash, worm-wood and other anti-malarial plants.

In 1735 Carolus Linnaeus wrote that quinine was the preferred treatment for malaria but that the bark of the ash (Fraxinus excelsior) and worm-wood (Artemisia absinthium) also had effects on the disease. We here report that lipo- and hydrophilic extracts of the bark of the ash inhibit the in vitro growth of the asexual stages of P. falciparum. The data suggests that the knowledge of the treatment of malaria was already available in Europe some 300 years ago.

Diverse biologies and experiential continuities: did the ancient Chinese know that qinghao had anti-malarial properties?

This article treats Chinese medical theories and concepts as cultural constructs that arose as much from practice-oriented concerns as from socio-political negotiations within the medical field. It further explores the interface of the biological and cultural. It is often futile to investigate how Chinese medical descriptions relate to biological processes, because the local biologies that the Chinese physicians recognized in the past and continue to describe in the present, are contested by mainstream medicine, but recent bioscientific research on the anti-malarial properties of the Chinese medical drug qinghao opens up new avenues for the historian. To be sure, no attempt is made to equate ancient nosologies to modern ones, nor to justify the cultural through the biological. In order to avoid pitfalls of simple equations, this article takes the experiential not merely as a subjective but as an inter-subjective reality that mediates the biological and cultural. The findings are striking: once one reads the Chinese medical texts as reporting on the experiential, one of their many possible readings is that they provide concrete descriptions of morbid conditions that also the contemporary mainstream physician recognizes.