Laura Alcântara
Caio Franco
Nilmar Moretti
Denise Pilger- 1Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal
- 2Laboratório de Biologia Molecular de Patógenos (LBMP), Departamento de Microbiologia, Universidade Federal de São Paulo, São Paulo, Brazil
- 3The Research Group on Infectious Diseases in Production Animals (GREMIP), Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, Canada
- 4Laboratory for Molecular Cell Biology, University College London, London, United Kingdom
Editorial on the Research Topic
Drug discovery for emerging and neglected tropical diseases: advances, challenges and perspectives
Neglected tropical diseases (NTDs) comprise a group of 20 human illnesses caused by bacteria, viruses, protozoans, ectoparasites, and venous snakebites. Altogether, NTDs affect over 1.7 billion people worldwide; they are predominantly prevalent in the tropical, low- and middle-income regions of the globe, where the most vulnerable populations live at risk (WHO, 2020). Nonetheless, climate changes and intense human migratory processes accelerate the dissemination of NTDs into non-endemic regions. Furthermore, the COVID-19 pandemic has raised the alert for the emergence of new and the re-emergence of old diseases, mainly because of host-switching events, drug resistance, and failure of public health measures (Morens and Fauci, 2020; The Lancet, 2022).
Besides the massive impacts on the economy, productivity, and social development, the latest records on NTDs indicate that, over 1 year, around 200,000 deaths occur, and the disability-adjusted life years (DALY) sum up to 19 million. In recent years though, we have observed remarkable progress in reducing the global burden for some NTDs, especially under the network of strategic actions managed by the World Health Organization (WHO) in association with governmental and private collaborators. Despite the efforts from several multisectoral initiatives focused on the prevention, control, treatment, and elimination of these maladies, many NTDs still prevail in regions with limited resources (WHO, 2020). Within this period, the field of drug discovery for NTDs has also seen a mix of progressions and drawbacks. There has been an increase in innovative public-private partnerships and the development of important therapeutic alternatives within distinct strategic approaches: drug repurposing [i.e., fexinidazole against human African trypanosomiasis (Kaiser et al., 2011; Bernhard et al., 2022)], new formulations [i.e., paediatric benznidazole against Chagas disease (DNDi, 2021)], drugs combination [i.e., miltefosine-paromomycin combination against visceral leishmaniasis (Musa et al., 2023)]. Nevertheless, several obstacles hamper the discovery and development of new drugs against NTDs, such as the high biological complexity of the disease, antimicrobial resistance, and financial impediments (De Rycker et al., 2018; Weng et al., 2018; DeWeerdt, 2021; Eisenstein, 2021). Therefore, despite advancements acquired through concerted efforts worldwide, the development of novel or improved treatments remains a relevant need in the continuous fight against NTDs.
In this context, this Research Topic brings together articles covering pivotal aspects of drug discovery and drug development for NTDs, focused on viral and parasitic infections. This Research Topic includes an original article devoted to the identification of novel therapeutic alternatives against Plasmodium falciparum. It also contains articles describing and discussing experimental strategies to uncover targets and modes of action of known and new antimicrobials. Lastly, it also includes a review article focused on the valuable lessons gained during the COVID-19 pandemic that could help to face and prevent future arbovirus epidemics.
Chirawurah et al. present follow-up studies to evaluate the potency of three Malaria Box compounds—previously selected as potent antimalarials (Chirawurah et al., 2017)—against a panel of twenty clinical isolates of P. falciparum. Using in vitro growth inhibitory assays, the authors validated the activity of these compounds and compared their activity with those observed for reference compounds. Most importantly, the article underscored the need to incorporate clinical isolates (including drug-resistant isolates) in antimalarial compound screening activities.
Fairlamb and Wyllie systematically discuss the crucial role of investigating the mode of action in kinetoplastid drug discovery, highlighting the tools currently available for target identification and validation, including genomics, proteomics, and metabolomics, as well as informatic approaches. The authors also provide examples of how to apply these tools to identify and exclude undesirable molecular pathways, detect potential toxic properties, and manage a balanced portfolio of target-based campaigns. Finally, the authors review the primary drug targets (e.g., proteasome and protein kinases) currently in clinical development against Leishmania and trypanosomes.
Hauser and Maser described an interesting in silico work of an integrative bioinformatic approach that was applied to discover potential targets of suramin, one of the pharmacopoeia’s most promiscuous drugs. A list of 44 diverse proteins was identified as potential targets of suramin, presenting common functional motifs. These findings are crucial to understanding the nature of suramin’s mechanism of action and, ultimately, to design new and more selective inhibitors.
Rosa-Nunes et al. comprehensively reviewed the scientific and technical advances achieved after the COVID-19 pandemic regarding prophylaxis, antiviral drug development, and immunization strategies. The article exemplifies relevant approaches currently used for disease management, including the use of mRNA-based vaccines and the administration of replication inhibitors (e.g., nucleoside analogues and protease inhibitors). Lastly, the authors discuss how we could explore the lessons learned from the COVID-19 pandemic and how to apply them to control neglected viral infections caused by arboviruses.
As a final remark, this Research Topic shows recent progress in the efforts for the discovery and development of new drugs for NTDs, with emphasis on parasitic and virus infections. Studies such as those collected herein contribute to reducing the existing research gaps that hinder the achievement of more effective and affordable treatments for vulnerable populations worldwide. We thank all the contributors.
Author contributions
LA: Writing–original draft, Writing–review and editing. CF: Writing–original draft, Writing–review and editing. NM: Writing–original draft, Writing–review and editing. DP: Writing–original draft, Writing–review and editing.
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. NM thank the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) grant number 2022/03075-0 and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) grant number 424729/2018-0. NM is CNPq Research fellow (CNPq 314103/2021-0).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
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References
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Chirawurah, J. D., Ansah, F., Nyarko, P. B., Duodu, S., Aniweh, Y., and Awandare, G. A. (2017). Antimalarial activity of Malaria Box compounds against Plasmodium falciparum clinical isolates. Int. J. Parasitol. Drugs Drug Resist. 7, 399–406. doi:10.1016/j.ijpddr.2017.10.005
De Rycker, M., Baragaña, B., Duce, S. L., and Gilbert, I. H. (2018). Challenges and recent progress in drug discovery for tropical diseases. Nature 559, 498–506. doi:10.1038/s41586-018-0327-4
DeWeerdt, S. (2021). Uneven attention hampers the drive to control infectious diseases. Nature 598, S10–S13. doi:10.1038/d41586-021-02910-y
DNDi (2021). Paediatric benznidazole. Available at: https://dndi.org/research-development/portfolio/paediatric-benznidazole/(Accessed November 18, 2023).
Eisenstein, M. (2021). Overlooked and underfunded: neglected diseases exert a toll. Nature 598, S20–S22. doi:10.1038/d41586-021-02912-w
Kaiser, M., Bray, M. A., Cal, M., Bourdin Trunz, B., Torreele, E., and Brun, R. (2011). Antitrypanosomal activity of fexinidazole, a new oral nitroimidazole drug candidate for treatment of sleeping sickness. Antimicrob. Agents Chemother. 55, 5602–5608. doi:10.1128/AAC.00246-11
Morens, D. M., and Fauci, A. S. (2020). Emerging pandemic diseases: how we got to COVID-19. Cell 182, 1077–1092. doi:10.1016/j.cell.2020.08.021
Musa, A. M., Mbui, J., Mohammed, R., Olobo, J., Ritmeijer, K., Alcoba, G., et al. (2023). Paromomycin and miltefosine combination as an alternative to treat patients with visceral leishmaniasis in eastern africa: a randomized, controlled, multicountry trial. Clin. Infect. Dis. 76, e1177–e1185. doi:10.1093/cid/ciac643
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Keywords: neglected tropical diseases (NTDs), emerging diseases, malaria, Trypanosomatids, COVID-19, arboviruses
Citation: Alcântara L, Franco C, Moretti N and Pilger D (2023) Editorial: Drug discovery for emerging and neglected tropical diseases: advances, challenges and perspectives. Front. Drug Discov. 3:1346042. doi: 10.3389/fddsv.2023.1346042
Received: 28 November 2023; Accepted: 29 November 2023;
Published: 08 December 2023.
Edited and reviewed by:
Stefania Galdiero, University of Naples Federico II, ItalyCopyright © 2023 Alcântara, Franco, Moretti and Pilger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Laura Alcântara, bGF1cmFtYWxjYW50YXJhQG91dGxvb2suY29t