Tuberculosis Drug Discovery and Development 2019 • Giovanna Riccardi and Sala Claudia Tuberculosis Drug Discovery and Development 2019 Edited by Giovanna Riccardi and Claudia Sala Printed Edition of the Special Issue Published in Applied Sciences www.mdpi.com/journal/applsci Tuberculosis Drug Discovery and Development 2019 Tuberculosis Drug Discovery and Development 2019 Editors Giovanna Riccardi Claudia Sala MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin Editors Giovanna Riccardi Claudia Sala Universita` degli Studi di Pavia Fondazione Toscana Life Sciences Italy Italy Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Applied Sciences (ISSN 2076-3417) (available at: https://www.mdpi.com/journal/applsci/special issues/Tuberculosis Drug Discovery). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03943-236-3 (Hbk) ISBN 978-3-03943-237-0 (PDF) c 2020 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Editors .............................................. vii Claudia Sala, Laurent Roberto Chiarelli and Giovanna Riccardi Editorial on Special Issue “Tuberculosis Drug Discovery and Development 2019” Reprinted from: Appl. Sci. 2020, 10, 6069, doi:10.3390/app10176069 ................. 1 Balachandra Bandodkar, Radha Krishan Shandil, Jagadeesh Bhat and Tanjore S. Balganesh Two Decades of TB Drug Discovery Efforts—What Have We Learned? Reprinted from: Appl. Sci. , 10, 5704, doi:10.3390/app10165704 .................... 5 Christian Lienhardt and Mario C. Raviglione TB Elimination Requires Discovery and Development of Transformational Agents Reprinted from: Appl. Sci. 2020, 10, 2605, doi:10.3390/app10072605 ................. 25 Angelo Iacobino, Lanfranco Fattorini and Federico Giannoni Drug-Resistant Tuberculosis 2020: Where We Stand Reprinted from: Appl. Sci. 2020, 10, 2153, doi:10.3390/app10062153 ................. 31 Paolo Mazzarello A Physical Cure for Tuberculosis: Carlo Forlanini and the Invention of Therapeutic Pneumothorax Reprinted from: Appl. Sci. 2020, 10, 3138, doi:10.3390/app10093138 ................. 49 Catherine Vilch`eze Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs Reprinted from: Appl. Sci. 2020, 10, 2278, doi:10.3390/app10072278 ................. 59 Giulia Degiacomi, Juan Manuel Belardinelli, Maria Rosalia Pasca, Edda De Rossi, Giovanna Riccardi and Laurent Roberto Chiarelli Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3 Reprinted from: Appl. Sci. 2020, 10, 623, doi:10.3390/app10020623 .................. 95 Vadim Makarov and Katar´ına Mikuˇsov´a Development of Macozinone for TB treatment: An Update Reprinted from: Appl. Sci. 2020, 10, 2269, doi:10.3390/app10072269 .................115 Caroline Shi-Yan Foo, Kevin Pethe and Andr´eanne Lupien Oxidative Phosphorylation—an Update on a New, Essential Target Space for Drug Discovery in Mycobacterium tuberculosis Reprinted from: Appl. Sci. 2020, 10, 2339, doi:10.3390/app10072339 .................127 Young Lag Cho and Jichan Jang Development of Delpazolid for the Treatment of Tuberculosis Reprinted from: Appl. Sci. 2020, 10, 2211, doi:10.3390/app10072211 .................161 Raphael Gries, Claudia Sala and Jan Rybniker Host-Directed Therapies and Anti-Virulence Compounds to Address Anti-Microbial Resistant Tuberculosis Infection Reprinted from: Appl. Sci. 2020, 10, 2688, doi:10.3390/app10082688 .................173 v Rob C. van Wijk, Rami Ayoun Alsoud, Hans Lennern¨as and Ulrika S. H. Simonsson Model-Informed Drug Discovery and Development Strategy for the Rapid Development of Anti-Tuberculosis Drug Combinations Reprinted from: Appl. Sci. 2020, 10, 2376, doi:10.3390/app10072376 .................191 Eduardo M. Bruch, St´ephanie Petrella and Marco Bellinzoni Structure-Based Drug Design for Tuberculosis: Challenges Still Ahead Reprinted from: Appl. Sci. 2020, 10, 4248, doi:10.3390/app10124248 .................211 Aaron Goff, Daire Cantillon, Leticia Muraro Wildner and Simon J Waddell Multi-Omics Technologies Applied to Tuberculosis Drug Discovery Reprinted from: Appl. Sci. 2020, 10, 4629, doi:10.3390/app10134629 .................231 Dina Visca, Simon Tiberi, Rosella Centis, Lia D’Ambrosio, Emanuele Pontali, Alessandro Wasum Mariani, Elisabetta Zampogna, Martin van den Boom, Antonio Spanevello and Giovanni Battista Migliori Post-Tuberculosis (TB) Treatment: The Role of Surgery and Rehabilitation Reprinted from: Appl. Sci. 2020, 10, 2734, doi:10.3390/app10082734 .................251 Rino Rappuoli Drugs and Vaccines Will Be Necessary to Control Tuberculosis Reprinted from: Appl. Sci. 2020, 10, 4026, doi:10.3390/app10114026 .................269 Carlos Martin, Nacho Aguilo, Dessislava Marinova and Jesus Gonzalo-Asensio Update on TB Vaccine Pipeline Reprinted from: Appl. Sci. 2020, 10, 2632, doi:10.3390/app10072632 .................271 vi Dedication “La tisi non le accorda che poche ore” From “La Traviata” by G. Verdi Dear readers I spent most of my life in the battle against Mycobacterium tuberculosis. My retirement is approaching and this special issue will conclude perfectly my TB research. I would like to dedicate it to Vita Quinci, one of the most positive student I had in my Lab, affected from Progressive Ossifying Fibrodysplasia, who suddenly died on May 1st. Her last message to me was: “Life is beautiful”. Giovanna Riccardi Vita Quinci: “La vita è bella” (life is beautiful) About the Editors Giovanna Riccardi 1976—Master Degree cum laude in Biology. 1977–1984—Fellowships aimed to work in Microbiology fields, at the Institute of Microbiology and Plant Physiology, University of Pavia; 1979—EMBO Short-Term fellowship, University of Liverpool (UK); 1984–1998—Researcher at the Department of Genetics and Microbiology, University of Pavia; 1999–2002—Associate Professor of Microbiology at the Department of Experimental, Environmental and Applied Biology, University of Genoa; Since October 2002—Full Professor of Microbiology, at the Department of Genetics and Microbiology (now Department of Biology and Biotechnology), University of Pavia; From January 2010 to December 2012—President of the SIMGBM (Italian Society of General Microbiology and Microbial Biotechnologies); Since August 2011—Member of the European Academy of Microbiology; The two main lines of research she is currently pursuing are: (1) RESISTANCE MECHANISMS AND TARGET IDENTIFICATION OF NEW DRUGS FOR Mycobacterium tuberculosis; (2) IDENTIFICATION OF NEW DRUGS AND NEW TARGETS FOR Burkholderia cenocepacia. FUNDING—Prof. G. Riccardi has obtained several grants from different sources: WHO; CNR-Bilateral Project; CNR-RAISA; MURST 40%; MURST-PRIN-1998, 2001, 2003, 2008; 2017; EC-V, VI and -VII frameworks; Istituto Superiore di Sanita,` Fondazione Fibrosi Cistica 2004, 2006, 2009, 2012, 2015. Cystic Fibrosis Foundation-USA 2017. Regarding the EC grants, she was always part of the steering committee. She is the author of several peer-reviewed articles, four book chapters, two International Patent Applications and several national and international communications. H-index Google Scholar: 42. Citations Google Scholar: 6099. Claudia Sala, PhD. Claudia Sala trained as a molecular microbiologist in the laboratory of Prof. Daniela Ghisotti, at the University of Milan (Italy), where she obtained her degree in Biological Sciences in 2000 and a PhD degree in Genetics and Molecular Biology in 2003. Her PhD thesis dealt with the transcriptional regulation of the furA and katG genes in mycobacteria in response to oxidative stress. In the framework of the EU FP6 ”New Medicines for Tuberculosis” (NM4TB) and FP7 “More Medicines for Tuberculosis” (MM4TB), she worked as a post-doctoral fellow in the laboratories of Prof. Stewart Cole, first at the Pasteur Institute in Paris, and then at the Ecole Polytechnique Fed´ erale´ de Lausanne, where she was subsequently promoted to senior scientist. She took active part in several research projects, including functional genomics and investigations on the M. tuberculosis Type VII Secretion System, and established the ChIP-Seq and RNA-Seq technologies in M. tuberculosis. She obtained the certificate of Biosafety Level 3 (BSL3) Safety Officer from the Swiss Confederation as well as the FESALA Category B and Category C licenses for performing and directing experiments involving animals. She was the recipient of the Swiss TB Award in 2010. She has recently moved to the Fondazione Toscana Life Sciences (TLS) in Siena, in the group led by Prof. Rino Rappuoli, and performs research on monoclonal antibodies and vaccine development. Her main interests include drug discovery against infectious diseases, vaccinology, host–pathogen interaction and biosafety. vii applied sciences Editorial Editorial on Special Issue “Tuberculosis Drug Discovery and Development 2019” Claudia Sala 1, Laurent Roberto Chiarelli