Pharmaceuticals for Targeting Coronaviruses

207 Pages·2022·33.374 MB·English

by  Luciana Scotti, Marcus T. Scotti

Pharmaceuticals for Targeting
Coronaviruses
Edited by
Luciana Scotti
&
Marcus T. Scotti
Laboratory of Cheminformatics
Program of Natural and Synthetic Bioactive Products
(PgPNSB)
Health Sciences Center, Federal University of Paraíba
João Pessoa-PB, Brazil
Pharmaceuticals for Targeting Coronaviruses

Editors: Luciana Scotti & Marcus T. Scotti
ISBN (Online): 978-981-5051-30-8
ISBN (Print): 978-981-5051-31-5
ISBN (Paperback): 978-981-5051-32-2
© 2022, Bentham Books imprint.
Published by Bentham Science Publishers Pte. Ltd. Singapore. All Rights Reserved.
BENTHAM SCIENCE PUBLISHERS LTD.
End User License Agreement (for non-institutional, personal use)
This is an agreement between you and Bentham Science Publishers Ltd. Please read this License Agreement
carefully before using the ebook/echapter/ejournal (“Work”). Your use of the Work constitutes your
agreement to the terms and conditions set forth in this License Agreement. If you do not agree to these terms
and conditions then you should not use the Work.
Bentham Science Publishers agrees to grant you a non-exclusive, non-transferable limited license to use the
Work subject to and in accordance with the following terms and conditions. This License Agreement is for
non-library, personal use only. For a library / institutional / multi user license in respect of the Work, please
contact: [email protected].
Usage Rules:
1. All rights reserved: The Work is the subject of copyright and Bentham Science Publishers either owns the
Work (and the copyright in it) or is licensed to distribute the Work. You shall not copy, reproduce, modify,
remove, delete, augment, add to, publish, transmit, sell, resell, create derivative works from, or in any way
exploit the Work or make the Work available for others to do any of the same, in any form or by any
means, in whole or in part, in each case without the prior written permission of Bentham Science
Publishers, unless stated otherwise in this License Agreement.
2. You may download a copy of the Work on one occasion to one personal computer (including tablet,
laptop, desktop, or other such devices). You may make one back-up copy of the Work to avoid losing it.
3. The unauthorised use or distribution of copyrighted or other proprietary content is illegal and could subject
you to liability for substantial money damages. You will be liable for any damage resulting from your
misuse of the Work or any violation of this License Agreement, including any infringement by you of
copyrights or proprietary rights.
Disclaimer:
Bentham Science Publishers does not guarantee that the information in the Work is error-free, or warrant that
it will meet your requirements or that access to the Work will be uninterrupted or error-free. The Work is
provided "as is" without warranty of any kind, either express or implied or statutory, including, without
limitation, implied warranties of merchantability and fitness for a particular purpose. The entire risk as to the
results and performance of the Work is assumed by you. No responsibility is assumed by Bentham Science
Publishers, its staff, editors and/or authors for any injury and/or damage to persons or property as a matter of
products liability, negligence or otherwise, or from any use or operation of any methods, products instruction,
advertisements or ideas contained in the Work.
Limitation of Liability:
In no event will Bentham Science Publishers, its staff, editors and/or authors, be liable for any damages,
including, without limitation, special, incidental and/or consequential damages and/or damages for lost data
and/or profits arising out of (whether directly or indirectly) the use or inability to use the Work. The entire
liability of Bentham Science Publishers shall be limited to the amount actually paid by you for the Work.
General:
1. Any dispute or claim arising out of or in connection with this License Agreement or the Work (including
non-contractual disputes or claims) will be governed by and construed in accordance with the laws of
Singapore. Each party agrees that the courts of the state of Singapore shall have exclusive jurisdiction to
settle any dispute or claim arising out of or in connection with this License Agreement or the Work
(including non-contractual disputes or claims).
2. Your rights under this License Agreement will automatically terminate without notice and without the
need for a court order if at any point you breach any terms of this License Agreement. In no event will any
delay or failure by Bentham Science Publishers in enforcing your compliance with this License Agreement
constitute a waiver of any of its rights.
3. You acknowledge that you have read this License Agreement, and agree to be bound by its terms and
conditions. To the extent that any other terms and conditions presented on any website of Bentham Science
Publishers conflict with, or are inconsistent with, the terms and conditions set out in this License
Agreement, you acknowledge that the terms and conditions set out in this License Agreement shall prevail.
Bentham Science Publishers Pte. Ltd.
80 Robinson Road #02-00
Singapore 068898
Singapore
Email: [email protected]
CONTENTS
PREFACE ................................................................................................................................................ i
REFERENCES ............................................................................................................................... ii
LIST OF CONTRIBUTORS .................................................................................................................. iii
CHAPTER 1 STRUCTURE-BASED DRUG DISCOVERY APPROACHES APPLIED TO
SARS-COV-2 (COVID-19) ..................................................................................................................... 1
Igor José dos Santos Nascimento, Thiago Mendonça de Aquino and Edeildo Ferreira da,
Silva-Júnior
1. INTRODUCTION ...................................................................................................................... 2
2. CORONAVIRUSES: HISTORY AND STRUCTURE ........................................................... 3
3. DRUG DISCOVERY PROCESS .............................................................................................. 4
4. SBDD STRATEGIES AND DISCOVERY OF HITS AGAINST CORONAVIRUSES ...... 6
4.1. Homology Modeling ........................................................................................................ 6
4.2. Pharmacophore Modeling ................................................................................................ 10
4.3. Molecular Docking and Dynamics Simulations .............................................................. 21
4.4. Fragment-Based Drug Discovery .................................................................................... 32
4.5. De Novo Drug Discovery ................................................................................................ 37
4.5. Virtual Screening (VS) and Virtual High-throughput screening (vHTS) ........................ 38
5. CHALLENGES IN SBDD FOR SARS-COV-2 ....................................................................... 50
CONCLUSION ............................................................................................................................... 52
CONSENT FOR PUBLICATION ................................................................................................ 52
CONFLICT OF INTEREST ......................................................................................................... 52
ACKNOWLEDGMENTS .............................................................................................................. 53
REFERENCES ............................................................................................................................... 53
CHAPTER 2 POTENTIAL ANTIVIRAL MEDICINAL PLANTS AGAINST NOVEL SARS-
COV-2 AND COVID-19 OUTBREAK .................................................................................................. 62
Nazim Sekeroglu and Sevgi Gezici
1. INTRODUCTION ...................................................................................................................... 63
2. MEDICINAL PLANT-BASED ANTIVIRAL THERAPEUTICS ......................................... 65
2.1. Rockrose (Cistus spp.) ..................................................................................................... 71
2.2. Lemon balm (Melissa Officinalis L.) ............................................................................... 72
2.3. Rosemary (Rosmarinus Officinalis L.) ............................................................................ 74
2.4. Olive leaf (Olea Europea L.) ........................................................................................... 77
2.5. Thyme Species (Origanum, Thymus & Thymbra) .......................................................... 79
2.6. Licorice Root (Glycyrrhiza Glabra L.) ............................................................................ 81
2.7. Other Antiviral Medicinal Plants ..................................................................................... 85
CONCLUSION AND FUTURE DIRECTIONS .......................................................................... 86
LIST OF ABBREVIATIONS ........................................................................................................ 86
CONSENT FOR PUBLICATION ................................................................................................ 87
CONFLICT OF INTEREST ......................................................................................................... 87
ACKNOWLEDGEMENTS ........................................................................................................... 87
REFERENCES ............................................................................................................................... 87
CHAPTER 3 INFECTIONS CAUSED BY SARS: MAIN CHARACTERISTICS, TARGETS
AND INHIBITORS ................................................................................................................................. 95
Herbert Igor Rodrigues de Medeiros, Gabriela Cristina Soares Rodrigues, Mayara dos,
Santos Maia, Marcus Tullius Scotti and Luciana Scotti
1. INTRODUCTION ...................................................................................................................... 95
2. ORIGIN AND EPIDEMIOLOGY ............................................................................................ 97
3. SARS PATHOGENESIS ............................................................................................................ 99
4. TAXONOMY .............................................................................................................................. 101
5. MAIN TARGETS OF SARS-COV AND SARS-COV-2 ......................................................... 103
5.1. Glycoprotein Spike (S) .................................................................................................... 104
5.2. Membrane Protein (M) .................................................................................................... 107
5.3. Envelope Protein (E) ........................................................................................................ 108
5.4. Nucleocapsid Protein (N) ................................................................................................. 109
5.5. 3-chymotrypsin-like Cysteine Protease (3CLpro) ........................................................... 111
5.6. Angiotensin Converting Enzyme (ACE)-2 ...................................................................... 113
6. DRUGS AND INHIBITORS AGAINST SARS ....................................................................... 114
CONCLUSION ............................................................................................................................... 126
LIST OF ABBREVIATIONS ........................................................................................................ 127
CONSENT FOR PUBLICATION ................................................................................................ 128
CONFLICT OF INTEREST ......................................................................................................... 128
ACKNOWLEDGEMENTS ........................................................................................................... 128
REFERENCES ............................................................................................................................... 128
CHAPTER 4 NATURAL SOURCED TRADITIONAL INDIAN AND CHINESE MEDICINES
TO COMBAT COVID-19 ....................................................................................................................... 138
Mayank Kumar Khede, Anil Kumar Saxena and Sisir Nandi
1. INTRODUCTION TO INDIAN AND CHINESE TRADITIONAL MEDICINE ................ 139
2. TRADITIONAL DRUGS AND NATURAL SOURCED FORMULATION FOR
TREATMENT OF COVID-19 ...................................................................................................... 142
2.1. Traditional Indian Medicines (TIM) to Combat COVID-19 ........................................... 143
2.2. Traditional Chinese Medicine (TCM) To Combat COVID-19 ....................................... 150
CONCLUSION ............................................................................................................................... 152
CONSENT FOR PUBLICATION ................................................................................................ 152
CONFLICT OF INTEREST ......................................................................................................... 152
ACKNOWLEDGEMENTS ........................................................................................................... 152
REFERENCES ............................................................................................................................... 152
CHAPTER 5 PEPTIDOMIMETIC AND PEPTIDE-DERIVED AGAINST 3CLPRO FROM
CORONAVIRUSES ................................................................................................................................ 158
Paulo Fernando da Silva Santos-Júnior, João Xavier de Araújo-Júnior and Edeildo
Ferreira da Silva-Júnior
1. INTRODUCTION ...................................................................................................................... 158
2. CHEMISTRY ASPECTS OF PEPTIDOMIMETICS ............................................................ 160
3. BIOCHEMISTRY ASPECTS AND MOLECULAR HOMOLOGY OF 3CLPRO FROM
MERS-COV, SARS-COV, AND SARS-COV-2 ........................................................................... 162
3.1. Structure, Function, and Druggability of 3CLpro from Coronaviruses ........................... 162
3.2. Catalytic Site of 3CLpro from Coronaviruses ................................................................. 162
4. CORONAVIRUSES 3CLPRO AND THEIR INHIBITORS ................................................. 163
4.1. Warhead Groups ............................................................................................................. 164
4.2. Peptidomimetics Containing Michael Acceptors as Warhead Groups ............................ 166
4.3. Peptidomimetics Containing Aldehydes as Warhead Groups ......................................... 168
4.4. Peptidomimetics Containing Keto Groups as Warheads ................................................. 171
4.4.1. Fluoromethyl Ketone Group ............................................................................... 171
4.4.2. 1,4-Peptidomimetics Containing Phthalazinediones as Warhead Groups ......... 173
4.4.3. Peptidomimetics Containing Benzothiazolones/thiazolones as Warhead Groups 175
4.4.4. Peptidomimetics Containing α-ketoamides as Warhead Groups ....................... 176
4.4.5. Peptidomimetics Containing Nitroanilides as Warhead Groups ........................ 177
4.5. Peptidomimetics Containing Nitriles as Warhead Groups .............................................. 177
4.6. Peptidomimetics Containing Aza-epoxides and Aziridines as Warhead Groups ............ 178
5. DRUG REPURPOSING FOR PEPTIDOMIMETICS ........................................................... 179
6. FINAL CONSIDERATIONS AND FUTURE OUTLOOK .................................................... 180
CONSENT FOR PUBLICATION ................................................................................................ 181
CONFLICT OF INTEREST ......................................................................................................... 181
ACKNOWLEDGEMENTS ........................................................................................................... 181
REFERENCES ............................................................................................................................... 181
SUBJECT INDEX .................................................................................................................................... 18(cid:28)
i
PREFACE
The new coronavirus (2019-nCoV) is part of the group of viruses in a format similar to a
crown (Corona), more specifically belonging to the species Betocoronavirus, such as Middle
East respiratory syndrome coronavirus (MERS-CoV) and acute respiratory syndrome
(SARS). The outbreak was first reported in Wuhan, China, in December 2019, where several
cases similar to pneumonia and SARS started to appear with symptoms of fever, cough, and
severe respiratory difficulties [1 - 4]. Its origin is still unknown. Some works suggest
mutations of the virus in bats or snakes, animals commercialized in the Wuhan market, which
have infected humans. The homology similar to the 2019 - nCoV than to your Sequences of
Bat SARS-like coronavirus supports the hypothesis that the transmission chain began from
the bat and reached the human [5, 6]. It was what happened to the infectious agent that caused
COVID-19.
The improvement of drug discovery techniques is fundamental in searching for new therapies
that could be selective and effective to combat SARS-CoV-2. Drug discovery approaches are
based on ligands (Ligand-Based Drug Design - LBDD) or structures (Structure-Based Drug
Discovery - SBDD). Concerning SBDD, it is the main and most evolved technique used for
discovering new drugs. The application of SBDD techniques has been improved the
pharmacological arsenal against diverse diseases, which allowed to discover innovative
treatments, such as inhibitors of HIV-1 proteases. In chapter I, main SBDD techniques (i.e.,
homology modeling; molecular dynamics and docking; de novo drug discovery;
pharmacophore modeling; fragment-based drug discovery; and virtual high-throughput
screenings) applied to discover new hit compounds SARS-CoV-2 (COVID-19) will be
discussed in detail.
Medicinal plants with a wide range of bioactive compounds, which are exhibiting antiviral
activities, are able to provide possible benefits as a preventive and treatment for COVID-19.
Rockrose (Cistus spp.), lemon balm (Melissa officinalis L.), rosemary (Rosmarinus officinalis
L.), licorice root (Glyrrhiza glabra L.), olive leaf (Olea europea L.), peppermint (Mentha
piperita L.), basil (Ocimum bacilicum L.), sumac (Rhus coriaria L.) and different species of
thyme (Origanum, Thymus, and Thymbra) are important medicinal plants having antiviral
activities. Chapter II provides an overview of published scientific information on the
development of plant-based antiviral therapeutic agents based on the extensive literature
survey. Researchers from all over the world are dedicating themselves to several studies in an
attempt to find the best treatment and prevention against the coronavirus. Chapter III
addresses the main characteristics of SARS, the main targets and drugs that have achieved
excellent results in clinical trials.
With increasing COVID-19 cases globally, it would be too difficult to provide proper
treatment even for the severe cases in hospitals. Therefore, the general public is advised to
wear the mask, maintain social distancing and use sanitizers. The COVID-19 mild infected
patients may be isolated at home and can be taken care of by natural medicines. In chapter IV,
an attempt has been made to repurpose all potential natural drugs and natural Ayurvedic
formulations that may be beneficial to combat viruses like the SARS-CoV-2 due to their
antiviral and immune-modulator properties available under Indian traditional medicine and
Chinese traditional medicine system for the effective treatment or prevention of COVID-19.
Peptidomimetics have emerged as a potential class for designing new effective drugs against
COVID-19, in addition to lopinavir/ritonavir, in which these drugs are currently being
investigated in clinical trials. In chapter V, the authors describe peptidomimetic and peptide-
ii
derived inhibitors of 3CLpro from SARS-CoV-2, and also SARS- and MERS-CoV viruses,
summarizing all relevant studies based on warhead groups utilization and SAR analysis for all
of them to contribute to the development of compounds more selective, effective, and low-
costs to combat these emerging viruses.
Luciana Scotti
&
Marcus T. Scotti
Laboratory of Cheminformatics
Program of Natural and Synthetic Bioactive Products (PgPNSB)
Health Sciences Center, Federal University of Paraíba
João Pessoa-PB, Brazil
REFERENCES
[1] Benvenuto D, Giovanetti M, Ciccozzi A, Spoto S, Angeletti S, Ciccozzi M. The 2019-new coronavirus
epidemic: Evidence for virus evolution. J Med Virol 2020; 92(4): 455-9.
[http://dx.doi.org/10.1002/jmv.25688] [PMID: 31994738]
[2] Zaher NH, Mostafa MI, Altaher AY. Design, synthesis and molecular docking of novel triazole
derivatives as potential CoV helicase inhibitors. Acta Pharm 2020; 70(2): 145-59.
[http://dx.doi.org/10.2478/acph-2020-0024] [PMID: 31955138]
[3] Phan T. Novel coronavirus: From discovery to clinical diagnostics. Infect Genet Evol 2020; 79:
104211.
[http://dx.doi.org/10.1016/j.meegid.2020.104211] [PMID: 32007627]
[4] Li G, Fan Y, Lai Y, et al. Coronavirus infections and immune responses. J Med Virol 2020; 92(4):
424-32.
[http://dx.doi.org/10.1002/jmv.25685] [PMID: 31981224]
[5] Mahase E. Coronavirus: doctor who faced backlash from police after warning of outbreak dies. Bmj-
British Medical Journal 2020; 368
[http://dx.doi.org/10.1136/bmj.m528]
[6] Mowbray H. In Beijing, coronavirus 2019-nCoV has created a siege mentality. Bmj-British Medical
Journal 2020.
[http://dx.doi.org/10.1136/bmj.m516]
[7] York A. Novel coronavirus takes flight from bats? Nat Rev Microbiol 2020; 18(4): 191.
[http://dx.doi.org/10.1038/s41579-020-0336-9] [PMID: 32051570]