Editorial Cite This: ACS Infect. Dis. 2018, 4, 429−430
pubs.acs.org/journal/aidcbc
Special Issue on Drug Discovery for Global Health
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included in this issue are two original contributions which expand the knowledge of plasmodium biology. The article published by L. E. Boucher, J. Bosch, and co-workers (DOI: 10.1021/acsinfecdis.7b00225) explores protein−protein interactions of the invasion machinery of the parasite by identifying hits that disturb a key interaction critical for the parasite to traverse and invade cells (TRAP proteins and aldolase). The letter published by L. S. Ross, A. K. Lukens, and co-workers (DOI: 10.1021/acsinfecdis.7b00217) discusses the concept of collateral sensitivity wheerein one suppresses resistance to a known drug by employing another compound that confers hypersensitivity. The development of new platforms to support drug discovery on these diseases is also represented in this issue. Without robust assays, screening platforms, supply of biological material, etc., such research is not feasible. Readers will find three papers showing advances in this area. A. T. Chao, U. H. Manjunatha, and co-workers (DOI: 10.1021/acsinfecdis.7b00247) developed a cytopathic effect-based assay to screen compounds against the enteric parasite Cryptosporidium. This is an important step forward for the field as the assay presents advantages over current methods, such as feasibility for HTS and a more accurate mimic of an in vivo infection as well as significant improvement in robustness. Two articles focused on developing Plasmodium vivax resources for drug discovery highlight the increased interest of the antimalarial community in this Plasmodium species and describe advances in the development of assay platforms. The article published by M. Moreno, J. M. Vinetz, and co-workers (DOI: 10.1021/ acsinfecdis.7b00195) presents a method that involves continuous P. vivax sporozoite production. The second article by P. Orjuela-Sanchez and E. A. Winzeler at al. (DOI: 10.1021/ acsinfecdis.7b00198) describes their effort in developing an in vitro P. vivax culture system carried out on site in a malariaendemic region, to foster the finding of new therapies against this Plasmodium species. Results are very encouraging as they detected P. vivax liver stage growth up. Seven original contributions related to hit identification and optimization can also be found in this Special Issue. The featured article coauthored by H. Vu, R. J. Quinn, and co-workers (DOI: 10.1021/acsinfecdis.7b00197) identifies dozens of promising ligands for malarial proteins by fragment-based screening of a natural products library employing native mass spectrometry. We think this article reveals information that can be directly applied to SAR purposes as well as target validation. M. C. Montoya, D. J. Krysan, and co-workers (DOI: 10.1021/ acsinfecdis.7b00157) disclose their effort to optimize antifungal phenothiazines in order to reduce unwanted side effects. Two articles are focused on improving the physicochemical profile of previously reported 4-anilinoquinolines as inhibitors of plasmodium proliferation (N. Mehta, M. P. Pollastri, and co-
very warm welcome to this Special Issue of the ACS Infectious Diseases journal focus on drug discovery efforts to fight against infectious diseases affecting developing countries. Diseases under this definition (among others) are grouped into a supra-discipline called Global Health. This term is not aligned with a specific scientific discipline, but to all disciplines involved in the discovery and development of new drugs to tackle this large group of diseases. Therefore, when planning this Special Issue, our expectations were to include contributions covering topics as diverse as the identification of new targets, the development of new platforms, or the quest of new scaffolds to treat these diseases. The call for abstracts was launched in the May 2017 journal issue in the form of an editorial (C. Aldrich and F. Calderón), in celebration of the 2nd Symposium on Medicinal Chemistry for Global Health in June 2017. We are delighted to have 22 contributions, including 15 original articles and letters, 3 perspectives, 1 viewpoint, 1 review, and 1 editorial in addition to this one. The diversity of the diseases covered (apicomplexan, kinetoplastid, bacteria, fungi and virus caused diseases) and the nature of the articles included (medicinal chemistry, genomics, target identification, platform development, parasitology) as well as the wide range of institutions located across the globe provide insight into the multidisciplinary nature of the field. Without going into much detail (as it would go much beyond the scope of an editorial), we would like to briefly highlight this Special Issue. Within the target identification/validation category, there are two contributions: a perspective (N. G. Jones, J. C. Mottram, and co-workers; DOI: 10.1021/ acsinfecdis.7b00244) and an article (M. J. Chaparro, E. Fernán dez, and co-workers; DOI: 10.1021/acsinfecdis.7b00211), which offer an overview of the target landscape for Leishmania/Trypanosoma and Plasmodium falciparum, respectively. While the article focuses on identifying opportunities for drug discovery purposes, the perspective analyses and reviews the quality of the criteria for evaluation of gene essentiality. Two manuscripts (a perspective and review) in the same category examine blockage of protein N-myristoylation of Plasmodium falciparum as a promising target to treat malaria (A. C. Schlott, E. W. Tate, and co-worker; DOI: 10.1021/ acsinfecdis.7b00203) and the proteostasis network that maintains integrity of the mycobacterial proteome to treat tuberculosis (T. J. Lupoli, B. Gold, and co-workers; DOI: 10.1021/acsinfecdis.7b00231). Two contributions focus on the application of chemical biology for the identification of targets in Mycobacterium tuberculosis (K. Kolbe, C. E. Barry III, and coworkers: DOI: 10.1021/acsinfecdis.7b00242) and Plasmodium falciparum (A. S. Lubin, M. J. Fuchter, and co-workers; DOI: 10.1021/acsinfecdis.7b00228). In the first one, readers will find an in-depth explanation of how development of chemical probes facilitates discovery of new targets and the development of diagnostics. The letter published by Lubin et al. is an original work disclosing a novel chemical probe that has shown success in pull-down experiments with plasmodium extracts. Also © 2018 American Chemical Society
Special Issue: Drug Discovery for Global Health Received: March 5, 2018 Published: April 13, 2018 429
DOI: 10.1021/acsinfecdis.8b00055 ACS Infect. Dis. 2018, 4, 429−430
ACS Infectious Diseases
Editorial
workers; DOI: 10.1021/acsinfecdis.7b00212) and aryl-[1,2,3] triazolo[4,5-d] pyrimidin-7(6H)-one as inhibitors of Chikungunya virus replication (A. Gómez-SanJuan, M.-J. Pérez-Pérez, and co-workers; DOI: 10.1021/acsinfecdis.7b00219). The analog synthesis of a reported antimalarial (MMV008138) targeting the methylerythritol phosphate pathway provides improved insights into the protein target (M. Ghavami, M. B. Cassera, and co-workers; DOI: 10.1021/acsinfecdis.7b00159). Two articles focused on kinetoplastid address new chemical diversity from natural products derivatives. A. L. Fraser, G. J. Florence, and co-workers (DOI: 10.1021/acsinfecdis.7b00187) disclose their efforts on tetrahydropyran derivatives with broad anti-trypanosoma activity. The second one, authored by R. A. West, S. E. Ward, and co-workers (DOI: 10.1021/acsinfecdis.7b00218), reports alternative oxidase inhibitors of Trypanosoma brucei. Finally, R. S. R. Vidadala, D. J. Maly, and coworkers (DOI: 10.1021/acsinfecdis.7b00224) disclose novel cryptosporidium calcium-dependent protein kinase 1 inhibitors based on a pyrrolopyrimidine core, which offers a therapeutic alternative to previously developed pyrazolopyrimidine as their pharmacokinetics properties are very different. In addition to the articles described, the issue is accompanied by one viewpoint. L. Ferrins and M. Pollastri (DOI: 10.1021/ acsinfecdis.7b00208) highlight the importance of collaboration between the private sector and academia to make advancements in reducing the burden of these diseases and review the collaborative efforts of current and future opportunities. We thank our authors for the time they dedicated to this collaborative issue. We also thank the numerous reviewers of all Special Issue submissions, the Editors of ACS Infectious Diseases, and the editorial office staff for their continuous support of this project. Finally, we thank the ACS Infectious Diseases readership and hope you enjoy this Special Issue and that it stimulates your interest in this critical area for people located in developing countries.
Courtney C. Aldrich* Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, 8-174 Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, Minnesota 55455, United States
Félix Calderón*
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Tres Cantos, Medicines Development Campus, DDW, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, Madrid 28760, Spain
AUTHOR INFORMATION
ORCID
Courtney C. Aldrich: 0000-0001-9261-594X Félix Calderón: 0000-0003-0486-6883 Notes
Views expressed in this editorial are those of the authors and not necessarily the views of the ACS.
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DOI: 10.1021/acsinfecdis.8b00055 ACS Infect. Dis. 2018, 4, 429−430
