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

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
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