This report reviews the current state-of-art of antiviral approaches including vaccines, pharmaceuticals and innovative technologies for the delivery of therapeutics. The introduction starts with a practical classification of viral diseases according to their commercial importance. Various antiviral approaches are described including pharmaceuticals and molecular biological therapies such as gene therapy and RNA interference (RNAi) as well as vaccines for virus infections. Expert opinion is given about the current problems and needs in antiviral therapy. SWOT (strengths, weaknesses, opportunities and threats) analysis of antiviral approaches is presented against the background of the concept of an ideal antiviral agent.
A novel feature of this report is the use of nanotechnology in virology and its potential for antiviral therapeutics. The interaction of nanoparticles with viruses is described. NanoViricides are polymeric micelles, which act as nanomedicines to destroy viruses. Various methods for local as well as systemic delivery of antiviral agents and vaccines are described. Nanobiotechnology plays an important role in improving the delivery of antivirals. Advantages and limitations of delivery of gene-based, antisense and RNAi antiviral therapeutics are discussed.
Anti-influenza measures applicable to humans as well as avian forms are described including the recent epidemic of swine flu. Resistance can develop against neuraminidase inhibitors although it is less than that with adamantanes. Considering these problems, there is a need for a more effective agent. Investigations into alternative anti-influenza targets will probably expand in the coming years. These include the development of mechanisms to inhibit fusion between the virus envelope and the cell membrane.
After a discussion of current therapies of AIDS/HIV and their limitations, new strategies in the development of antiviral agents are described. Drug resistance and toxicities are emerging as major treatment challenges. Based on a review of technologies and drugs in development, it can be stated that there are good prospects are of finding a cure for HIV/AIDS in the next decade.
Hepatitis viruses are described with a focus on hepatitis C virus (HCV) and hepatitis B virus (HBV). Despite the presence of numerous drug candidates in the anti-HCV pipeline and the commitment of major R&D resources by many pharmaceutical companies, it might still take several years for any new anti-HCV drugs to reach the market. Although many companies are focusing their efforts on developing viral inhibitors, cellular targets in the host are beginning to emerge as attractive possibilities because they might enable the development of broad-spectrum antiviral drugs with less chance for developing viral resistance.
Various commercially important viruses include herpes simplex (HSV) and human papilloma virus (HPV). There are a number of treatments but HSV is not destroyed completely and remains dormant and activates from time to time to cause various clinical manifestations. There is a discussion about the role of HPV in cervical cancer and vaccines available now seem to be adequate in preventing HSV-induced cervical cancer. There is no effective vaccine for the respiratory syncytial virus (RSV) although monoclonal antibody (MAb) treatment is useful for prophylaxis and reducing the clinical manifestations. There is a need for an agent to eliminate this virus.
Various viruses that either occur in epidemics or in tropics and some naturally emerging infectious diseases are described, e.g. viral hemorrhagic fevers such as dengue and West Nile virus infection. These are a constant threat and impossible to anticipate. Some of these lack antiviral agents or vaccines for prevention. Although these include some of the most serious viral disorders, the development of antiviral agents for these is not commercially attractive. Current research and approaches to these virus infections, particularly the current pandemic of COVID-19, are discussed. There are over 110 drugs and vaccine candidates in the development of which 3 have been approved by the FDA and other health authorities around the world. Vaccination is being carried out in several countries
Markets for antivirals are considered according to viruses and diseases caused by them and also according to management approaches: antiviral drugs, vaccines, MAbs and innovative approaches that include immunological and use of other technologies such as gene therapy, antisense, RNAi and nanobiotechnology. Antiviral markets are estimated to start with 2020 with projections up to the year 2030.
Profiles of 197 companies that are involved in developing various technologies and products are profiled and with 182 collaborations. These include major pharmaceutical companies (12), Biopharmaceutical companies with antiviral products (87), Antiviral drug companies (26) as well as viral vaccine companies (71). The report is supplemented with 58 tables, 17 figures and 550 references from the literature.
Topics Covered
- Introduction to Virology
- Antiviral Approaches
- Vaccines for Virus Infections
- Role of Nanotechnology in Developing Antiviral Agents
- Delivery of Antivirals
- Competitive Assessment of Antiviral Approaches
- Influenza Viruses
- AIDS/HIV
- Hepatitis Viruses
- Miscellaneous Commercially Important Virus Infections
- Viruses with High Impact but Low Commercial Significance
- Human Corona Viruses
- Markets for Antivirals
- Companies
Table of Contents
Part I: Technologies & Products
0. Executive Summary
1. Introduction to Virology
- Introduction
- Evolution of viruses
- Virus databases
- A practical classification of viruses
- The human virome
- Viral genomics
- Viruses and human health
- Endogenous retroviruses
- Endogenous retrovirus-disease link
- Pathomechanism of viral diseases relevant to therapy
- Viral entry into host cells
- Immune response to viruses
- Intrinsic host defense against retroviruses
- Interferon-induced B cell deletion in chronic viral infections
- Drosha as an interferon-independent antiviral factor
- Life cycle of virus as basis for antiviral approaches
- Genetic switch in virus infections
- Emerging viruses
- Viral-induced cancer
- Viral infections of the brain
- Brain’s response to viral infections
- Viral encephalitis
- Antibody-mediated encephalitis
- Eastern equine encephalitis
- Endogenous retrovirus related neurological disorders
- Amyotrophic lateral sclerosis
- Dementia
- Multiple sclerosis
- Combination of antivirals with immunosuppression in viral encephalitis
- Molecular diagnosis of viral diseases
- Prophylaxis versus therapy
- Economic impact of viral diseases
- Historical landmarks in the development of antiviral therapies
2. Antiviral Approaches
- Classification
- Antiviral drug discovery and development
- Antiviral drug targets − viral versus cellular
- Antivirals based on double-stranded RNA activated caspase oligomerizer
- Antimicrobial peptides
- Human DDX3 protein as a target for developing broad spectrum antiviral agents
- Immunological approaches
- Basics of immune regulation in relation to viruses
- Effect of viruses on the immune system
- Latent viral infections and the immune system
- Immunomodulating agents
- Amplification of innate immunity
- Blocking the effects of thromboxane A2 on thromboxane receptor
- Enhancers of immune system
- Promoting immune-mediated clearance of a chronic viral infections
- Immunoglobulins
- Bovine lactoferrin
- Quercetin
- Monoclonal antibodies
- Antibody production technologies
- Bavituximab
- Treatment of viral infection with radiolabeled MAbs
- Limitations of MAbs and measures to overcome these
- Interferon-based approaches
- Cholesterol-25-hydroxylase
- Novel antiviral approaches
- Phosphatidylethanolamine inhibitors as potential antivirals
- Squalamine
- Synthetic modified hypericin compounds
- Targeting Toll-like receptors
- Potential and drawbacks of TLR-ligands in viral diseases
- Use of CRISPR/Cas9 gene editing in antiviral approaches
- Targeting RNA viruses
- Inhibition of viral transport from cytoplasm into the cell nucleus
- Nitric Oxide based antiviral therapeutics
- Amino acid cognate anticodon binding specificity
- Antisense approaches to viral infections
- Antisense oligonucleotides
- Limitations of antisense oligonucleotides as antivirals
- Phosphorodiamidate morpholino oligomers
- Gene therapy for viral infections
- RNAi
- RNAi screens of viral genomes
- RNAi for treatment of viral infections
- Promise and pitfalls of RNAi gene therapy
- Role of proteomics in virology
- Interaction of proteins with viruses
- Quantitative temporal viromics
- Management of rapidly evolving pathogens
- Personalized medicine and viral diseases
- Genomic epidemiology of viral diseases
- An integrated approach to viral diseases
- Current problems and needs in antiviral therapy
- Immunoinformatic approach to vaccine design for emerging infections
- Broad-spectrum antiviral agents
3. Vaccines for Virus Infections
- Introduction
- Types of vaccines
- DNA vaccines
- Live attenuated virus vaccines
- Measles-vectored vaccines
- mRNA vaccines
- Nanotechnology-based vaccines
- Nanobead adjuvants
- Recombinant viral vaccines
- SMART vaccines
- Synthetic peptides as vaccines
- Virally vectored vaccines
- Virosomes
- Vaccines based on reverse genetics
- Virus-like particles
- Routine vaccination in children against viral infections
- Personalized vaccines
- Limitations of vaccines
- Neurological complications of vaccination
- Future of antiviral vaccines
4. Role of Nanotechnology in Developing Antiviral Agents
- Introduction
- Study of interaction of nanoparticles with viruses
- Exosomes and viral infections
- Nanoparticle antiviral agents
- Silver nanoparticles
- Fullerenes
- Nanoparticles mimic RNAi for the treatment of viral infections
- Nanoviricides
- Role of micelles in nanopharmaceuticals
- Some physicochemical characteristics common to polymeric micelles
- Structure and function of nanoviricides
- Mechanism of action of NanoViricides
- Advantages of NanoViricides
5. Delivery of Antivirals
- Introduction
- Methods of delivery of antiviral agents
- Local application of antivirals
- Systemic delivery of of protein-polymer antiviral drugs
- Controlled delivery of antivirals
- Targeted delivery of antivirals
- Delivery of antivirals to the brain across the blood-brain barrier
- Antiviral vaccine delivery systems
- Minicell vaccine delivery
- Transnasal delivery of vaccines by Newcastle disease virus as vector
- Transdermal delivery of vaccines
- Dissolvable microneedle array for vaccine delivery
- Electroporation for administering DNA vaccines
- HIV/AIDS vaccination by transdermal application
- Microneedles for transdermal delivery of vaccines
- Needle-free delivery of vaccines
- Transdermal vaccines for influenza
- Use of nanotechnology for improving delivery of antivirals
- Macrophage-based nanoformulated antiretroviral therapy
- Improvement of antiviral vaccine delivery by nanotechnology
- Bacterial spores for delivery of vaccines
- Chitosan-derived nanoparticles for vaccine delivery
- Dendrimer-based intracellular delivery of antibodies
- Gold nanorods for delivery of RNA immune activator molecules
- Lipid nanoparticles for immunostimulatory RNA delivery
- Liposomal antiviral vaccine preparations
- Nanoparticles for DNA vaccines
- Nanospheres for controlled release of viral antigens
- Proteosomes™ as vaccine delivery vehicles
- Polymeric micellae for delivery of DNA vaccine
- “Smart” nanoparticles for delivery of vaccines
- Nanocoating for local viricidal effect
- Delivery of gene-based antiviral drugs
- Limitations of delivery of gene, RNAi and antisense therapies
- Systemic delivery of NanoViricides
- Concluding remarks on delivery of antiviral agents
6. Competitive Assessment of Antiviral Approaches
- Introduction
- An ideal antiviral agent
- SWOT analysis
- Concluding remarks
7. Influenza Viruses
- Introduction
- Clinical features of influenza
- Colds due to rhinovirus
- Effects of influenza on the respiratory system
- Effect of avian influenza on the nervous system
- Epidemiology
- Supermap of avian influenza
- Influenza A
- Avian influenza affecting humans
- Human infection with a H7N9 Virus
- Human influenza versus avian influenza
- H1N1 influenza
- Immune system and influenza
- Immune Epitope Database and Analysis Resources
- Role of Tpl2 in antiviral host defense mechanisms
- Anti-influenza approaches
- Pharmaceuticals
- Neuraminidase inhibitors
- Mechanism of action
- Tamiflu
- Zanamivir
- CS-8958
- Peramivir
- Resistance to neuraminidase inhibitors
- Adverse effects of neuraminidase inhibitors
- Concluding remarks on neuraminidase inhibitors
- Other drugs for influenza
- Adamantanes
- Baloxavir marboxil
- Probenecid
- Current recommendations for the use of antiviral agents for influenza
- Vaccines
- Seasonal influenza vaccines
- Live attenuated influenza vaccine vs. inactivated vaccine
- Recombinant influenza vaccine
- Vaccines for H1N1 influenza
- Vaccine for H5N1 influenza A
- Vaccines for H7N9 influenza
- Current status of influenza vaccines
- Limitations of current influenza vaccines
- Needs of influenza vaccines
- Problems with demand and supply of influenza vaccines
- Problems with access to virus samples
- FluVac project for development of pandemic influenza vaccine
- Influenza vaccines for multiple strains of influenza
- Quadrivalent influenza vaccine
- Universal influenza vaccines
- FLU-v universal vaccine
- Future of influenza vaccines
- Application of new technologies for influenza vaccines
- Adjuvants
- Cell culture-derived influenza vaccines
- DNA vaccines for avian influenza
- Epitope-based vaccines for influenza
- Gene-based vaccines for influenza
- Live attenuated vaccines
- MAbs for passive immunization against avian influenza
- M2e-based human influenza A vaccine.
- RNA vaccines against influenza A
- Pre-pandemic split antigen H5N1 vaccine
- Recombinant-protein based influenza vaccines
- Synthetic avian influenza vaccine
- Viral vectors for influenza vaccination
- Virus-like particles as influenza vaccines
- RNAi-based approaches
- Inhibition of influenza virus by siRNAs
- Limitations of RNAi approach to influenza
- Challenges and future prospects of siRNAs for influenza
- Antisense approaches
- NEUGENE® antisense for inhibition of multiple strains of influenza A
- Nanoviricides against influenza
- Other innovative approaches
- Abatacept
- Bacteriophage for blocking influenza virus entry
- Polymeric coatings to inactivate influenza virus
- Cytotoxic therapy
- Cyanovirin
- Fludase
- Multiferon®
- Pyrrolidine dithiocarbamate
- Value of antivirals in preventing spread of influenza after exposure
- Resistance to influenza therapy and efforts to overcome it
- FLUCURE project
- NIAID Centers of Excellence for research on pandemic influenza viruses
- Research on influenza viruses at Bayer
- Concluding remarks and future
8. AIDS/HIV
- Introduction
- Epidemiology
- Current concepts of pathomechanisms
- Decoding the structure of an entire HIV genome
- Genetic basis of resistance against HIV
- Host-pathogen interactions that regulate HIV-1 replication
- Pathogenesis of AIDS
- Visualization of the interaction of HIV-1 proteins with target cells
- Viral latency in HIV
- Complications of AIDS
- HIV in the brain
- Neurological complications of AIDS
- AIDS dementia
- AIDS wasting syndrome
- Coexistent HIV-1 and HSV-2
- Coexistent hepatitis virus infections with HIV
- HIV and HBV
- HIV and HCV
- Opportunistic infections in AIDS
- HIV and tuberculosis
- Current therapies
- Aim of anti-HIV drugs
- Nucleoside reverse transcriptase inhibitors
- Non-nucleoside reverse transcriptase inhibitors
- Efavirenz
- Etravirine
- Protease inhibitors
- Tipranavir
- Darunavir
- Fusion inhibitors
- Enfuvirtide
- Combinations of drugs for AIDS
- Truvada
- Raltegravir, enfuvirtide, and darunavir
- Current antiretroviral regimens
- Impact of antiretroviral treatment on transmission of HIV
- Preexposure prophylaxis against HIV
- Postexposure prophylaxis against HIV
- Antiretroviral therapy in early asymptomatic HIV infection
- Limitations of current therapies
- Adverse effects of antiretroviral therapy
- Drug resistance in AIDS
- Effect of interruption of HIV treatment
- Reservoirs of HIV Infection
- Persistance of low-level viremia in HIV-1 patients on retroviral therapy
- Reconsideration of abandoned therapies for AIDS
- Therapies in development
- Drugs in development for HIV/AIDS
- NRTIs in development
- NNRIs in development
- Novel protease inhibitors
- Overcoming HIV-1 resistance to PIs
- PPL-100
- Entry inhibitors targeting CCR5 receptor
- Maraviroc
- SP-01A
- MAbs targeting CCR5 receptor
- PRO 140
- Ibalizumab
- Integrase inhibitors
- Raltegravir (Isentress)
- Elvitegravir
- Dolutegravir
- S/GSK1265744
- LEDGINs
- Design of fusion inhibitor peptides against enfuvirtide-resistant HIV-1
- gp120 attachment inhibitors
- Maturation inhibitors
- Blocking of pre-integration complex translocation
- Immune enhancers
- Pyrimidinediones
- Other innovative antiviral approaches against HIV/AIDS
- A filtration device for HIV-1 as an adjunct to the immune system
- Anti-HIV therapies based on editing enzymes
- Anti-HIV activity of drugs that stimulate cholesterol efflux
- Antiviral hyperactivation-limiting therapeutics
- ATR kinase as a target for anti-HIV drug discovery
- Drugs from natural sources
- Enhancing immune response by blockade of PD-1 receptor
- IL-2 as adjunct to antiretroviral therapy
- In vitro evaluation of antiviral drug activity
- Methods for sustaining antiviral activity
- Microbicidal agents for local application in HIV/AIDS
- Investigational microbicidals against HIV and their limitations
- CCR5 receptor blockers
- PSC-Rantes and recombinant chemokine analogs
- HIV-1 entry inhibitor griffithsin as a topical microbicide
- Nanotechnology-based topical microbicides
- Next generation microbicides for HIV
- Vaginal application of anti-retroviral drugs against HIV
- Nanoviricides for HIV/AIDS
- Prophylactic measures to prevent HIV infection
- Selective targeting of ITK to block multiple steps of HIV replication
- T cell receptors from HIV controllers
- Cell therapy for HIV/AIDS
- hESCs converted to T cells for treatment of HIV infection
- Transplantation of genetically modified hematopoietic cells
- Transplantation of genetically modified T cells
- Overlapping Peptide-pulsed Autologous Cells
- Gene therapy strategies in HIV/AIDS
- Gene editing for HIV-1
- Inhibition of HIV-1 replication by lentiviral vectors
- VRX496-T (Lexgenleucel-T)
- Insertion of protective genes into target cells
- Use of genes to chemosensitize HIV-1 infected cells
- Autocrine interferon- production by somatic cell gene therapy
- Intracellular immunization in HIV
- Engineered cellular proteins such as soluble CD4s
- Intracellular antibodies
- Selection of T cell vaccine antigens
- Glycoprotein 120 as target for neutralizing HIV-1 antibodies
- Anti-rev single chain antibody fragment
- HIV/AIDS vaccines
- Cell-based vaccines for HIV
- Delivery of HIV vaccine by an adenoviral vector
- DNA vaccines for HIV/AIDS
- Epitope-based DNA vaccines against HIV
- Gene transfer for HIV vaccination
- Recombinant HIV proteins
- Vaccination after discontinuation of antiretroviral treatment
- Innovations in HIV/AIDS vaccine
- Attenuated rabies virus-based vaccine for HIV
- Dendritic cell-based vaccine for HIV
- DermaVir
- Early control of HIV by an effector memory T cell vaccine
- Immunogens for inducing broadly neutralizing antibodies
- MVA nef vaccine
- Peptide-based vaccine for HIV
- Personalized vaccine for HIV
- RV144 HIV vaccine trial
- Transdermal nanoparticles for immune enhancement in HIV
- Vaccine to prevent HIV entry at the mucosal level
- Limitations and future of HIV vaccines
- Antisense approaches to AIDS
- Antisense oligodeoxynucleotides
- Antisense efforts with PNA constructs
- RNA decoys
- Ribozymes
- RNAi applications in HIV/AIDS
- A multiple shRNA approach for silencing of HIV-1
- Aptamer-mediated delivery of anti-HIV siRNAs
- Bispecific siRNA constructs
- Role of the nef gene during HIV-1 infection and RNAi
- siRNA-directed inhibition of HIV-1 infection
- Synergistic effect of snRNA and siRNA
- Targeting CXCR4 with siRNAs
- Targeting CCR5 with siRNAs
- Concluding remarks on RNAi approach to HIV/AIDS
- Companies involved in developing gene therapy for HIV/AIDS
- Conclusions regarding gene therapy of HIV/AIDS
- Testing for new anti-HIV therapies
- Personalized approach to management of HIV
- Differences in response of the body to HIV
- Variations in action of drugs on HIV
- Drug-resistance in HIV
- PhenoSense® to test HIV drug resistance
- Role of biomarkers in management of HIV/AIDS
- Role of diagnostic testing in management of HIV
- Prevention of adverse reactions to antiviral drugs
- Nanoviricides as a personalized approach to HIV
- Concluding remarks and future
9. Hepatitis Viruses
- Introduction
- Hepatitis delta virus infection
- Hepatitis A virus infection
- Hepatitis E virus infection
- Epidemiology
- Structure of the HEV
- Treatment of HEV infection
- Ribavirin
- Zinc as a potential anti-HEV agent
- Vaccines for hepatitis E
- Epidemiology of HBV
- Pathogenesis of HBV-induced liver disease
- Current approaches to management of HBV
- Entecavir
- Adefovir dipivoxil
- Telbivudine
- Pegylated interferon-alpha
- Limitations of current therapies and needs of HBV
- Personalized management of HBV
- Innovations in the management of HBV
- Tenofovir disoproxil fumarate
- Hepatitis B immune globulins
- Nabi-HB
- HepaGam B
- Hepatitis B vaccine composed in a novel nanoemulsion adjuvant
- Innovative pharmaceuticals for HBV
- AGX-1009
- Clevudine
- Helioxanthin analog 8-1
- HepDirect prodrugs
- Monoclonal antibodies for HBV
- RNAi-based therapy of HBV
- Personalized treatment of hepatitis B
- Concluding remarks and future prospects of management of hepatitis B
- Epidemiology of HCV
- HCV characteristics
- Pathomechanism of HCV infection
- Mechanism of HCV entry
- HCV and the immune system
- Mechanism of HCV replication and response to interferon
- Current approaches to management of HCV
- Diagnostic approaches to HCV
- Recommended treatment protocols for HCV
- Interferon therapy for HCV
- Limitations of current HCV therapies
- Novel approaches to HCV
- HCV protease inhibitors
- ABT-450
- Boceprevir
- Combined daclatasvir and asunaprevir
- Faldaprevir
- Glecaprevir/pibrentasvir combination
- Narlaprevir
- Sofosbuvir
- Simeprevir
- Small molecule HCV protease inhibitors
- Telaprevir
- Innovations in interferon therapy for HCV
- AlbIFN-2b
- Directed evolution of gene-shuffled IFN-α for treatment of HCV
- GEA007.1
- Omega DUROS
- PEG-IFN-
- Personalizing interferon therapy of HCV
- Innovative ribavirin-based treatments
- Targeted delivery of hemoglobin-ribavirin conjugate for HCV
- Taribavirin
- Nucleoside polymerase inhibitor
- Deleobuvir
- Valopicitabine
- Host cell targets for hepatitis C therapy
- SP-10
- NS5a inhibitors
- Ledipasvir
- NS5b inhibitors
- Novel combination of a protease inhibitor and a NS5a inhibitor
- Zepatier™
- Compounds targeting HCV receptor E2
- Cyclophilin inhibitors
- Alisporivir
- Methylene blue
- Naringenin
- Nitazoxanide
- Cyclosporine and analogs as anti-HCV agents
- Clemizole and HCV
- RNAi-based approaches to HCV
- Use of adenoviral vectors for RNAi
- siRNAs for HCV
- Limitations and drawbacks of siRNA therapy for HCV
- Role of miRNA in viral infections
- miR-122 antagonists
- Gene therapy for HCV
- Vaccines for HCV
- HCV vaccine based on viral vectors to boost T cell memory
- Vaccine based on neutralizing antibodies to HCV
- Clinical trials of HCV therapeutics
- Limitations to the development of effective anti-HCV therapeutics
- Causes of treatment failure in chronic hepatitis C
- HCV drug resistance
- Personalized management of HCV infection
- Role of sequencing in personalized management of HCV
- Concluding remarks about HCV therapy
- Drug combinations for HCV
- IFN-free combinations for HCV
- Search for new drugs for HCV
- Future needs in HCV therapy
10. Miscellaneous Commercially Important Virus Infections
- Introduction
- Herpes viruses
- Neuroinvasive herpesviruses
- Herpes simplex virus
- Treatment of HSV-1
- Acyclovir
- Vaccines for HSV
- Antisense therapy for HSV-1
- Herpes simplex virus 2 and genital herpes
- Famciclovir
- Pritelivir
- Intravaginal microbicidal agents for HSV-2
- Vaccines for HSV-2
- Herpes simplex keratitis
- Herpes simplex encephalitis
- Limitations of current HSV therapies
- Genomic diversity of HSV-1 as a cause of failure of vaccines
- Recombinations in HSV-1 and HSV-2
- Herpes zoster virus
- Herpes zoster and chicken pox
- Epidemiology of herpes zoster
- Treatment of herpes zoster
- Herpes zoster vaccines
- Epstein-Barr virus
- Latent herpes virus infection
- Cytomegalovirus
- Current treatment of CMV
- Brincidofovir (CMX001)
- Valganciclovir hydrochloride
- Limitations of current treatment and future
- Letermovir
- T cell therapy for CMV
- Vaccines for CMV
- Gene therapy of CMV
- Antisense approach to CMV
- siRNA treatment of CMV
- Human papilloma virus
- Epidemiology
- Vaccines for HPV
- Gardasil
- Cervarix
- DNA vaccine VGX-3100
- GTL001 and GTL002
- Vaccine based on fusion proteins of HPV envelope
- Safety and limitations of HPV vaccines
- Antivirals for HPV
- Imiquimod
- Novel approaches against HPV
- Intrabody strategies for the treatment of HPV
- A novel peptide to inhibit HPV
- Heat shock protein-based antivirals
- Respiratory syncytial virus
- Epidemiology
- Current management of RSV
- Palivizumab
- MDT-637
- GS-5806
- RNAi approach to RSV
- Other approaches to RSV antivirals
- Vaccines for RSV
- BCG as a vaccine against RSV
- Oral DNA vaccine for RSV
- Neutralizing antibodies against preactive form of hRSV_F protein
- Challenges for development of RSV antivirals
- Other respiratory viruses
- Parainfluenzavirus type 3
- Human metapneumovirus
- Gastrointestinal viruses
- Noroviruses
- Potential for development of antiviral agents against noroviruses
- Vaccines against noroviruses
- Precautionary measures during a novovirus outbreak
- Concluding remarks
11. Viruses with High Impact but Low Commercial Significance
- Introduction
- Chikungunya fever
- Chikungunya antiviral therapy
- Chikungunya vaccines
- Enteroviruses
- Enterovirus 71
- Coxsackie virus
- Japanese encephalitis
- Vaccines for JE
- Parvovirus
- Polyomavirus JC
- Rabies
- Rabies vaccines
- Recombinant viral vaccines for rabies
- DNA vaccine against rabies
- Rabies immune globulin
- Monoclonal antibodies for rabies
- NanoViricides approach for rabies
- Protein-protein interactions as targets for antirabies drug discovery
- siRNA-based approach against rabies
- The Milwaukee protocol for rabies
- Rotavirus
- Epidemiology
- Rotavirus genome
- Vaccines against rotavirus
- Viral hemorrhagic fevers
- Bas-Congo virus associated with acute hemorrhagic fever
- Crimean-Congo hemorrhagic fever
- Dengue
- Epidemiology
- Antivirals in development against dengue
- Dengue vaccines
- Dengvaxia
- Elimination of dengue vector mosquitoes by fungus
- Genetic elimination of dengue vector mosquitoes
- Ebola virus
- Pathogenesis and diagnosis of Ebola virus
- Sequencing of the Ebola genome
- Antiviral approaches to Ebola virus infection
- Antivirals for Ebola based on inhibition of RNA polymerase
- Cell entry blockers as antivirals for filoviruses
- Development of RNAi-based antiviral drugs for Ebola
- EbolaCide
- Monoclonal antibody immunotherapy for Ebola
- Vaccines for Ebola
- Ebola whole virus vaccines
- Companies developing antivirals against Ebola
- Concluding remarks and future
- Human hanta viruses
- Lassa fever
- Marburg hemorrhagic fever
- Therapies in development against Marburg virus
- Yellow fever
- Vaccines for yellow fever
- Sequencing of Aedes aegypti genome and control of yellow fever
- West Nile virus
- Epidemiology
- Pathogenesis
- Treatment of West Nile neuroinvasive disease
- Vaccines against WNV
- Innovative treatments for WNV
- Zika virus
- Introduction to Zika virus
- ZIKV in the USA
- Clinical features of ZIKV
- Molecular epidemiology of ZIKV
- Molecular diagnosis of ZIKV infection
- Neurological complications of ZIKV infection
- Pathomechanism of neurological complications of Zika
- Microcephaly
- Guillain-Barré syndrome
- Prevention and treatment of ZIKV infection
- Antiviral agents against ZIKV
- Preventive measures against ZIKV infection
- Vaccines for ZIKV
- WHO views on challenges in management of ZIKV
- Western equine encephalitis
- Tick-borne encephalitis
- TBE vaccines
- Zoonotic viral infections
- Risk of spillover of new zoonotic viruses to humans
- Vaccines for zoonotic viral diseases
- Measles
- Nipah virus
- Virus bioterrorism and biowarfare
- Smallpox as a biological weapon
- Status of smallpox vaccination
- Dryvax vaccine
- Modified Vaccinia Ankara (MVA)
- Strategies against virus bioterrorism and biowarfare
- Increasing resistance by stimulating innate immune mechanisms
- Nanoviricides for combating viral bioterrorism
- Concluding remarks
12. Human coronaviruses
- Introduction
- SARS
- Therapeutic approaches to SARS
- MAbs for SARS
- siRNA treatment of SARS
- Middle East respiratory syndrome coronavirus
- Development of therapeutics for MERS-CoV
- MERS vaccines
- Future directions for management of MERS
- Coronavirus China 2019
- Introduction and epidemiology
- Genomics of coronaviruses
- Genetic susceptibility for severity of COVID-19
- Risk factors that increase morbidity and mortality in COVID-19
- Molecular diagnosis of COVID-19
- Serological assay for detection of SARS-CoV-2 antibodies
- Reassessment of molecular diagnostics for COVID-19
- Point-of-care tests for COVID-19
- Pathogenesis of COVID-19
- Pathogenesis of pulmonary complications
- Pathogenesis of neurological complications
- Strategies for developing therapies for COVID-19
- Antivirals for COVID-19
- Clinical trials of COVID-19 therapies
- Dexamethasone
- Hydroxychloroquine
- Favipiravir
- Molnupiravir
- Remdesivir
- Monoclonal antibodies for COVD-19
- Nanobodies for COVID-19
- Management of cytokine release syndrome in COVID-19
- Role of IL-6 in CRS
- Tocilizumab
- Edaravone
- Management of hypoxia in COVID-19
- Hyperbaric oxygen in COVID-19
- Discovery and development of new therapies for COVID-19
- Cell therapy for COVID-19
- Exosomes derived from bone marrow mesenchymal stem cells
- Gene editing with for COVID-19 by RNA-targeting CRISPR systems
- Nanosponges for COVID-19
- Role of vitamin D sufficiency in reducing COVID-19 mortality
- Immunotherapies for COVID-19
- Antibodies from patients as immune therapy for COVID-19
- Monoclonal antibodies for COVID-19
- Monoclonal antibodies and future vaccines
- Vaccines for COVID-19
- mRNA vaccines for COVID-19
- Adenoviral vectors carrying gene for COVID-19 spike protein
- Age-related reduction in immunity by vaccine against SARS-CoV-2
- Comparison of vaccines for COVID-19
- Operation Warp Speed
- Oral COVID-19 vaccine
- DNA vaccine for COVID-19
- Other vaccines for COVID-19
- Pitfalls in developing vaccines for COVID-19
- Personalized vaccines for COVID-19
- Personalized approach to passive antibody therapy for COVID-19
- Protection from re-infection after COVID-19 as well as by vaccination
- Protection against COVID-19 variants
- Regulatory approval of COVID-19 vaccines
- Safety of vaccination in pregnancy and during lactation
- Future of tackling with coronaviruses
- New antiviral targets
- Repurposing drugs for COVID-19
- Inhibiting complement hyper-activation in the lungs
- Improving ability to respond to future coronavirus outbreaks
Tables
Table 1-1: A practical classification of viruses
Table 1-2: Viruses causing encephalitis
Table 1-3: Vaccines vs therapeutics for viral diseases
Table 1-4: Historical landmarks in the development of antiviral therapies
Table 2-1: Classification of antiviral strategies
Table 2-2: Viral vs cellular targets for discovery of antivirals
Table 2-3: Viruses amenable to antisense oligonucleotides
Table 2-4: Inhibition of viral replication by RNAi
Table 3-1: Types of vaccines for viral diseases
Table 4-1: Role of nanobiotechnology in virology
Table 5-1: Methods of delivery of antiviral agents
Table 5-2: Role of nanotechnology for improving delivery of antivirals
Table 5-3: Commercially available liposomal antiviral vaccines
Table 6-1: SWOT of monoclonal antibodies
Table 6-2: SWOT of agents that prevention viral entry into cells
Table 6-3: SWOT of drugs interfering with intracellular replication
Table 6-4: SWOT of protease inhibitors
Table 6-5: SWOT of integrase inhibitors
Table 6-6: SWOT of maturation inhibitors
Table 6-7: SWOT of neuraminidase inhibitors
Table 6-8: SWOT of targeting Toll-like receptors (TLRs)
Table 6-9: SWOT of topical antivirals agents against viral infections
Table 6-10: SWOT of gene therapy, antisense oligonucleotides, RNAi
Table 6-11: SWOT of vaccines
Table 6-12: SWOT of NanoViricides
Table 7-1: Anti-influenza approaches
Table 7-2: Antiviral drugs used for influenza
Table 7-3: Various approaches to production of influenza vaccines
Table 8-1: Drugs in clinical development for HIV/AIDS
Table 8-2: Strategies for gene therapy of AIDS
Table 8-3: Classification of HIV/AIDS vaccines in clinical trials
Table 8-4: Companies involved in developing gene therapy for HIV/AIDS
Table 9-1: Innovations in the treatment of HBV
Table 9-2: Recommended regiments for management of chronic HCV
Table 9-3: Innovations for management of HCV
Table 9-4: Antiviral agents for HCV targeting host cells
Table 9-5: HCV drugs in clinical trials
Table 10-1: Methods of delivery of acyclovir
Table 11-1: Antiviral strategies against Ebola virus infection
Table 11-2: Companies developing antiviral products against Ebola
Table 11-3: ZIKA vaccines in development
Table 11-4: Strategies against virus bioterrorism and biowarfare
Table 12-1: Drugs in development for COVID-19
Table 12-2: Clinical trials of hyperbaric oxygen in COVID-19 patients
Table 12-3: Vaccines in development for COVID-19
Figures
Figure 1-1: Endogenous retrovirus-disease link
Figure 1-2: Varieties of host and cell responses to viral infections
Figure 1-3: Cycle of infection and replication of a retrovirus
Figure 1-4: Viral-induced cancer
Figure 2-1: Pathogen sequencing as a guide to personalized management viral infections
Figure 2-2: An integrated approach to viral diseases
Figure 2-3: Safe-in-man broad-spectrum antiviral agents
Figure 3-1: Mechanisms of immune activation by virally vectored vaccines
Figure 4-1: Schematic representation of NanoViricide attacking a virus particle
Figure 7-1: Evolution of mutations associated with virulence/drug resistance in H5N1
Figure 7-2: Mechanism of development of resistance to oseltamivir
Figure 8-1: Mode of action of some current anti-HIV drugs
Figure 8-2: Nanocarrier-mediated siRNA delivery for treatment of HIV/AIDS
Figure 9-1: Steps of HBV replication and site of action of various drugs
Figure 9-2: Omega DUROS device for interferon delivery in chronic hepatitis C
Figure 11-1: Strategies for development of ZIKV vaccines
Part II: Markets & Companies
13. Markets for Antivirals
- Introduction
- Markets according to disease
- Influenza market
- HIV/AIDS market
- Hepatitis B and C markets
- Economics of care of hepatitis C and impact on the market
- Markets for diseases with low commercial significance
- Markets according to products and approaches
- Market values of monoclonal antibodies for viral diseases
- Market values of vaccines for viral diseases
- Markets for vaccines against HPV
- Research investment and potential markets for HIV/AIDS vaccines
- Markets for vaccines against COVID-19
- Markets for other antiviral vaccines
- Markets according to geographical areas
- Emerging markets for antiviral therapeutics
- Geographical distribution of HIV/AIDS market
- Unmet needs in antivirals
- Policies regarding conquered viral diseases
- Future of polio vaccine
- Policies concerning HPV vaccine for prevention of cervical cancer
- HPV vaccine in developing countries
- Future of innovative approaches
- US Government support of antiviral efforts
- US Government support for R & D in avian influenza vaccines
- US Government support for developing anti-bioterrorism agents
- The European Union support of antiviral research
- European Commission’s research support for anti-HIV/AIDS programs
- European Commission's support anti-influenza programs
- Collaboration of biotechnology companies with big pharma
- Strategies for marketing
14. Companies
- Introduction
- Top companies
- Profiles of pharmaceutical companies
- Profiles of biopharmaceutical companies with antiviral products
- Profiles of antiviral drug companies
- Profiles of viral vaccine companies
- Collaborations
15. References
Tables
Table 13-1: Worldwide market for all antiviral approaches 2020-2030
Table 13-2: Markets for antiviral drugs according to virus infections 2020-2030
Table 13-3: Markets values of all drugs for HIV/AIDS 2020-2030
Table 13-4: Market values of monoclonal antibodies for viral diseases 2020-2030
Table 13-5: Market values of vaccines for viral diseases 2020-2030
Table 13-6: Markets for antiviral drugs according to geographical areas 2020-2030
Table 13-7: Markets for antiviral vaccines according to geographical areas 2020-2030
Table 13-8: Emerging markets for antiviral drugs according to countries 2020-2030
Table 13-9: Emerging markets for antiviral vaccines according to countries 2020-2030
Table 14-1: Top antiviral companies
Table 14-2: Roche antiviral products in development
Table 14-3: Collaborations of antiviral companies
Figures
Figure 13-1: Unmet needs in antivirals
Samples
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