Biomedical Innovations to Combat COVID-19: Mechanics, Biology, and Numerical Modeling

Biomedical Innovations to Combat COVID-19 provides an updated overview on the development of vaccines, antiviral drugs and nanomaterials, and diagnostic methods for the fight against COVID-19. Perspectives on such technologies are identified, discussed, and enriched with figures for easy understanding and applicability. Furthermore, it contains basic aspects of virology, immunology, and antiviral drugs that are needed to fully appreciate these innovations. This book is split into four sections: introduction, presenting basic virologic and epidemiological aspects of COVID-19; vaccines against COVID-19, discussing their different types and applications used to develop them; diagnostic approaches for SARS-CoV-2, encompassing advanced sensing and microfluidic-based biosensors; and drug development and delivery, where antivirals based on nanomaterials or drugs are presented. It is a valuable source for virologists, biotechnologists, and members of biomedical field interested in learning more about how novel technologies can be applied to fasten the eradication of the COVID-19 and similar pandemics. Presents updated literature coverage summarizing the most relevant information on COVID-19 Written by experts from diverse scientific domains in order to provide readers with a thorough view on the subject Encompasses tables, figures and information trees especially developed for the book in order to condense and highlight key points for quick reference Front Cover Biomedical Innovations to Combat COVID-19 Copyright Page Contents List of contributors Preface Acknowledgments 1 Basic virological aspects of SARS-CoV-2 1.1 Introduction 1.2 Genome organization and function 1.2.1 Genome organization 1.2.2 Genome function 1.3 Viral entry 1.3.1 Virus–cell interaction 1.3.2 Clathrin-mediated endocytosis 1.4 Genome replication and translation 1.4.1 Replication and transcription 1.4.2 Translation 1.5 Assembly 1.5.1 Virus-induced cell remodeling 1.5.2 Virion assembly 1.6 Egress 1.6.1 A novel egress pathway 1.7 General aspects of the immune response to a viral infection 1.7.1 Type I interferon and the antiviral state 1.7.2 Dendritic cells 1.7.3 Natural killer cells 1.7.4 Macrophages 1.7.5 Cellular immune response 1.7.6 The humoral immune response 1.8 Concluding remarks Acknowledgments References 2 Fundamental aspects of the structural biology of coronaviruses 2.1 Introduction 2.2 The structural proteins 2.2.1 Envelope protein 2.2.2 Nucleocapsid protein 2.2.3 Membrane protein 2.2.4 Spike protein 2.3 The viral proteases 2.3.1 Main protease 2.3.2 Papain-like protease 2.4 The accessory proteins 2.4.1 Protein 3a 2.4.2 Protein 7a 2.4.3 Protein 8 2.4.4 Protein 9b 2.5 Concluding remarks References 3 Introduction to the SARS-CoV-2/COVID-19 epidemiology 3.1 Introduction 3.2 Epidemiology 3.3 Clinical characteristics 3.3.1 Definition of a suspected case established by the WHO 3.4 Impact of COVID-19 3.5 Infection in pediatrics 3.6 Vitamin D and COVID-19 3.7 Epidemiology analysis of the SARS-CoV-2 outbreak 3.8 Immune response and reinfections 3.9 SARS-CoV-2 variants 3.10 Closing remarks References 4 Structural biology of the SARS-CoV-2 replisome: evolutionary and therapeutic implications 4.1 Introduction 4.2 Structural biology of SARS-CoV-2 4.3 The SARS-CoV-2 replisome: expanding knowledge through structural biology 4.4 The RNA-dependent RNA polymerase 4.5 Nsp7 and nsp8 processivity actors 4.6 Nsp13 helicase 4.7 Nsp14 exonuclease and N7-methyltransferase 4.8 Nsp9 single-stranded RNA-binding protein 4.9 Nsp10–nsp14 and nsp16 cofactor 4.10 The nonenzymatic synthesis of nucleosides and their derivatives: from the prebiotic chemistry to therapeutic agents 4.11 On the origin and early evolution of RNA viruses and SARS-CoV-2 4.12 The emergence of new infectious diseases by zoonoses 4.13 Conclusion Acknowledgments References 5 Clinical progression of patients with COVID-19: the impact of the pandemic in Latin America 5.1 Introduction 5.2 COVID-19-associated pathogenesis 5.2.1 The SARS-CoV-2 effect on multiple organs is associated with ACE2 expression 5.2.2 Underlying comorbidities and lethality 5.2.3 The clinical usefulness of clustering symptoms 5.3 COVID-19 behavior in Latin America 5.3.1 Viral outbreaks in Latin America 5.3.2 Latin America: the epicenter of COVID-19 5.3.3 Underlying comorbidities in Latin America 5.3.4 Most common COVID-19 symptoms in Latin America 5.4 COVID-19 in Mexico 5.4.1 COVID-19 in Mexico: lethality, comorbidities and symptoms 5.5 Remarks References 6 Overview of the immune response against SARS-CoV-2 6.1 Introduction 6.2 Virion structure 6.3 Viral cycle 6.3.1 Transcription and translation 6.3.2 Replication complex of SARS-CoV-2 6.3.3 Egress 6.4 Protein organization of SARS-CoV-2 6.4.1 Spike protein 6.4.2 Nucleocapsid protein 6.5 The innate immune response against SARS-CoV-2 6.5.1 Evasion mechanisms 6.6 The immune response against SARS-CoV-2 6.6.1 Humoral immunity against SARS-CoV-2 infection 6.7 Neutralizing antibodies 6.8 Immunopathology of COVID-19 6.9 Conclusion Acknowledgment Conflicts of interest References 7 Viral-vectored vaccines against SARS-CoV-2 7.1 Introduction 7.2 Development of COVID-19 vaccines 7.2.1 COVID-19 vaccines breaking record times to first-in-human trials 7.2.2 Classical versus next-generation vaccine platforms 7.2.2.1 Classical vaccine platforms 7.2.2.2 Next-generation vaccine platforms 7.2.3 COVID-19 vaccine pipelines in clinical evaluation and viral-vectored vaccines 7.2.4 Leading viral-vectored vaccine candidates in Phase III trial 7.3 Concluding remarks Acknowledgment References 8 RNA-based vaccines against SARS-CoV-2 8.1 Introduction 8.2 Principles of mRNA vaccines 8.3 Liposomes as vaccine delivery vehicles 8.3.1 Synthesis of liposomes 8.3.2 Modification of liposomes 8.4 The mRNA-1273 vaccine developed by Moderna Inc 8.4.1 SARS-CoV-2-S-2P mRNA synthesis and lipid nanoparticle formulation 8.4.2 Preclinical trial: mouse studies 8.4.3 Phase I 8.4.4 Preclinical trial: nonhuman primates 8.4.5 Phase I: older adults 8.4.6 Phase III 8.5 BNT162b1 and BNT162b2 vaccines developed by Pfizer and BioNTech 8.5.1 Preclinical trial 8.5.2 Phase I/II 8.5.2.1 German trial (NCT04380701, EudraCT:2020–001038–36) 8.5.3 Phase I trial including older adults and BNT162b2 8.5.3.1 ClinicalTrials.gov identifier, NCT04368728 8.5.4 Decision between the two vaccine candidates BNT162 8.5.5 Phase II/III: BNT162b2 8.6 CVnCoV vaccine developed by CureVac 8.6.1 Preclinical trials 8.6.2 Mice 8.6.3 Syrian hamster 8.6.4 Rhesus macaques 8.6.5 Phase I 8.7 Concluding remarks and perspectives References 9 Particulate vaccines against SARS-CoV-2 9.1 Introduction 9.1.1 The COVID-19 pandemic 9.1.2 A severe contagious disease 9.1.3 Characteristics of SARS-CoV-2 9.2 Vaccines in development 9.2.1 Vaccines against SARS-CoV-2 9.2.2 Vaccines in clinical trials 9.2.3 On the vaccines under development 9.3 Particulate vaccines 9.3.1 Definitions and existing reports 9.3.2 Benefits of nanovaccines and considerations 9.4 Vaccines based on lipid nanoparticles 9.5 Inorganic nanoparticles as carriers 9.5.1 Composition and synthesis 9.5.2 Gold, silver, and iron oxide nanoparticles 9.6 Nanovaccines against SARS-CoV-2 9.7 Concluding remarks References 10 Virus-like particle-based vaccines against SARS-CoV-2 10.1 Introduction 10.2 Potential of VLP-based vaccines 10.3 HBV vaccines 10.4 HEV vaccines 10.5 HPV vaccines 10.6 Precedents of VLP-based vaccines against human coronaviruses 10.7 VLP-based vaccines against SARS-CoV-2 10.8 Concluding remarks Funding References 11 Innovative recombinant protein-based vaccines against SARS-CoV-2 11.1 Introduction 11.2 SARS-CoV, the vaccines proposed before COVID-19 11.3 Current vaccines proposed for SARS-CoV-2 11.4 Vaccine platforms implemented for SARS-CoV-2 11.5 SARS-CoV-2 protein-based vaccines 11.6 The rational design of the antigen by bioinformatics strategies 11.7 Current vaccine candidates based on recombinant proteins 11.8 The NVX-CoV2373 vaccine 11.9 Preclinical trials 11.9.1 Mouse studies 11.10 Nonhuman primates studies 11.10.1 Olive baboons 11.10.2 Cynomolgus macaques 11.11 Clinical trials 11.12 The VAT00002 vaccine 11.12.1 Clinical trial 11.13 The ZF2001 vaccine 11.13.1 Clinical trial 11.14 Efforts to develop a vaccine in Mexico 11.15 Concluding remarks and perspectives References 12 SARS-CoV-2 vaccines: current trends and prospects of developing plant-derived vaccines 12.1 Introduction 12.2 Coronavirus overview 12.3 Clinical manifestations 12.4 Vaccine candidates for COVID-19 12.5 Plant molecular farming 12.5.1 Plant-based vaccine scenario 12.5.2 Possibilities of developing of plant-derived COVID-19 vaccines 12.5.2.1 Subunit vaccines 12.5.2.2 Virus-like particles vaccines 12.5.3 Immune complexes 12.5.4 Oral vaccines 12.6 Prospects 12.7 Concluding remarks Acknowledgment Conflict of interest Author contributions References Further reading 13 Nanobodies targeting SARS-CoV-2 13.1 Introduction 13.2 The concept of a “classic antibody” 13.3 The “newly” described antibodies 13.4 The VHH or nanobodies 13.4.1 Production of Nbs, synthetic libraries 13.4.2 Structure of nanobodies 13.5 Nanobodies as biotechnological tools 13.6 Nanobodies against SARS-CoV-2 13.7 Limitations of the Nbs technology 13.8 Concluding remarks References 14 2D materials and van der Waals heterostructures platforms for advanced sensing of COVID-19 14.1 Introduction 14.2 Graphene, 2DMs, and vdW heterostructures 14.3 2DMs devices 14.4 Internet of things (IoT) 14.5 2DMs advances sensing of COVID-19 14.6 Perspective and conclusions Acknowledgment References 15 Microfluidic-based biosensor for SARS-CoV-2 antibodies 15.1 Introduction 15.2 Materials 15.2.1 Molecule as bioreceptor 15.2.2 Low-frequency QCMs 15.2.3 Immobilization and immunoassay flow-cell 15.2.4 Fluidic module 15.3 Methods 15.3.1 Read-out module 15.3.2 Data acquisition and user interface 15.3.3 Functionalization and immobilization 15.3.4 Direct immunoassay against SARS-CoV-2 antibodies 15.3.5 Analytical parameters 15.3.5.1 Dose–response protocol 15.3.6 Standard calibration curve 15.4 Concluding remarks Acknowledgments References 16 Antivirals based on nanomaterials against SARS-CoV-2 16.1 Nanomaterials against SARS-CoV-2 16.2 Nanomaterials against enveloped viruses 16.2.1 Graphene oxide and derivatives 16.3 Silver nanoparticles 16.4 Zinc oxide nanoparticles 16.5 Quantum dots 16.6 Gold nanoparticles 16.7 Other nanomaterials 16.8 Conclusion References Further reading 17 The potential of drug delivery nanosystems to treat COVID-19 17.1 Introduction 17.2 DDS with the potential to treat COVID-19 17.2.1 Free chloroquine 17.2.2 Chloroquine delivery nanosystems 17.2.3 Free ivermectin 17.2.4 Ivermectin delivery nanosystems 17.2.5 Free lopinavir/ritonavir 17.2.6 Lopinavir/ritonavir delivery nanosystems 17.2.7 Free ribavirin 17.2.8 Ribavirin delivery nanosystems 17.2.9 Free sofosbuvir 17.2.10 Sofosbuvir delivery nanosystems 17.2.11 Free siRNA 17.2.12 siRNA delivery nanosystems 17.2.13 Free dexamethasone 17.2.14 Dexamethasone delivery nanosystems 17.3 Conclusion and perspectives References Further reading 18 The role of traditional medicine in the fight against SARS-CoV-2 18.1 Introduction 18.2 Severe acute respiratory syndrome-coronavirus 18.3 Severe acute respiratory syndrome-coronavirus-2 18.3.1 Computational studies 18.3.2 Herbal medicines 18.3.3 Natural products 18.3.3.1 Polyphenols 18.3.3.2 Alkaloids and terpenoids 18.3.4 Clinical trials 18.4 Concluding remarks and perspectives References Index Back Cover