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      Drug Development Strategies for Malaria: With the Hope for New Antimalarial Drug Discovery—An Update


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          Malaria continued to be a deadly situation for the people of tropical and subtropical countries. Although there has been a marked reduction in new cases as well as mortality and morbidity rates in the last two decades, the reporting of malaria caused 247 million cases and 619000 deaths worldwide in 2021, according to the WHO (2022). The development of drug resistance and declining efficacy against most of the antimalarial drugs/combination in current clinical practice is a big challenge for the scientific community, and in the absence of an effective vaccine, the problem becomes worse. Experts from various research organizations worldwide are continuously working hard to stop this disaster by employing several strategies for the development of new antimalarial drugs/combinations. The current review focuses on the history of antimalarial drug discovery and the advantages, loopholes, and opportunities associated with the common strategies being followed for antimalarial drug development.

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          Most cited references114

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          Drug repurposing: progress, challenges and recommendations

          Given the high attrition rates, substantial costs and slow pace of new drug discovery and development, repurposing of 'old' drugs to treat both common and rare diseases is increasingly becoming an attractive proposition because it involves the use of de-risked compounds, with potentially lower overall development costs and shorter development timelines. Various data-driven and experimental approaches have been suggested for the identification of repurposable drug candidates; however, there are also major technological and regulatory challenges that need to be addressed. In this Review, we present approaches used for drug repurposing (also known as drug repositioning), discuss the challenges faced by the repurposing community and recommend innovative ways by which these challenges could be addressed to help realize the full potential of drug repurposing.
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            Qinghaosu (artemisinin): the price of success.

            N. White (2008)
            Artemisinin and its derivatives have become essential components of antimalarial treatment. These plant-derived peroxides are unique among antimalarial drugs in killing the young intraerythrocytic malaria parasites, thereby preventing their development to more pathological mature stages. This results in rapid clinical and parasitological responses to treatment and life-saving benefit in severe malaria. Artemisinin combination treatments (ACTs) are now first-line drugs for uncomplicated falciparum malaria, but access to ACTs is still limited in most malaria-endemic countries. Improved agricultural practices, selection of high-yielding hybrids, microbial production, and the development of synthetic peroxides will lower prices. A global subsidy would make these drugs more affordable and available. ACTs are central to current malaria elimination initiatives, but there are concerns that tolerance to artemisinins may be emerging in Cambodia.
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              Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

              Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance.

                Author and article information

                Adv Med
                Adv Med
                Advances in Medicine
                14 March 2023
                : 2023
                : 5060665
                1Department of Life Sciences, The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
                2Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
                3Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202001, Uttar Pradesh, India
                4Department of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Lucknow 226031, Uttar Pradesh, India
                Author notes

                Academic Editor: Shunqing Liang

                Author information
                Copyright © 2023 Swaroop Kumar Pandey et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 21 July 2022
                : 27 February 2023
                : 8 March 2023
                Review Article


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