2. Background
• Other than a natural disaster of cataclysmic proportions, or an all-out man-made
nuclear war,
• Infectious diseases pose the only global threat to human life on Earth.
• Infectious diseases have plagued humanity and represented the major cause of
morbidity and mortality through the millennia, and in the process shaped human
evolution.
• They still constitute the leading cause of premature death in the developing
world.
3. Background
• Viral infections are one of the leading causes of morbidity and mortality
worldwide and one of the main reasons for significant economic losses.
• Standard treatment approaches mainly rely on vaccination and therapeutics
derived through targeting key processes in the virus life cycle.
• However, many viruses evolve subject to selective pressures, often becoming
drug resistant, which necessitates additional resources for the development of
new drugs.
4. The Pandemic through History
• There have been a number of significant pandemics recorded in human history,
including smallpox, cholera, plague, dengue, AIDS, influenza, severe acute
respiratory syndrome (SARS), West Nile disease and tuberculosis.
• Influenza pandemics are unpredictable but recurring events that can have severe
consequences on societies worldwide.
• Influenza pandemics have struck about three times every century since the 1500s,
or roughly every 10-50 years
• The influenza pandemic of 1918-1919, which killed more than 20 million people
in the world and has been cited as the most devastating epidemic in recorded
world history
7. Background
• Through millions of years of evolution, viruses have gained a variety of molecular
mechanisms for
– Entry into cells
– Long-term survival within cells; and
– Activation, inhibition, or modification of the host defense mechanisms at all levels.
• Their ability to transfer genes with high efficiency inspired the development of
non-infectious recombinant viral vectors for gene-therapy applications, beginning
in 1990.
8. Introduction to a new virus?
• At the end of December 2019, the World Health Organization (WHO) China
Country Office was informed by the Chinese authorities of an infectious disease
•
On January 9 of this year, Chinese state media reported that a team of researchers
led by Xu Jianguo had identified the pathogen behind a mysterious outbreak of
pneumonia in Wuhan as a Coranavirus
• Now named severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-
2).
• The WHO declared COVID-19 as a pandemic on March 11,
9. Introduction to a new virus?
• The COVID-19 pandemic is not a unique case in the history of viruses but one
representative of the new century, which is sobering news for humans.
• Coronaviruses take their name from the distinctive spikes with rounded tips that
decorate their surface.
• Various coronaviruses infect numerous species, but the first human coronaviruses
weren’t discovered until the mid-1960s.
12. • SARS-CoV-2 possesses a positive sense, single-stranded RNA genome.
• The virus particles have an approximate diameter of 60–140 nm and appear
crown-shaped as observed under an electron microscope
•
14. What actually a nanomaterial is?
• In general, nanomaterials can be described as single-structures—free or in a
composite—with a size within the nanometric range,
• Usually less than 100 nm in at least one of their three dimensions.
• The nanoscale—the physicochemical properties of materials display significant
changes that contrast their counterparts at larger scales,
• Nowadays, nanomaterials are found in a wide range of existing products, such as
in electronics, health and fitness, paints and other surface
• Coatings, food, and clothing, among many others.
• Moreover, medicine is among the areas with a growing interest in the use of
nanotechnology
18. Nanotechnology versus the virus
• The COVID-19 crisis has also mobilized the scientific community in a way that no
other situation has before
• Nanotechnology offers a number of solutions to fight viruses, both outside and
inside the host, and several nanotechnology based platforms have already been
successful in preclinical studies
• To counter several human viral pathogens such as HIV, human papilloma virus,
herpes simplex, and respiratory viruses
• In the current situations, nanotechnology is being used for making PPE,
diagnosing kits, in disinfectants as well as in vaccine development
19. Nanotechnology versus the virus
• Decades of rapid development have witnessed the widespread application of
nanotechnology in the biomedical field.
• Although it is not being widely applied in current antiviral research, its potential is
unquestionable.
• To summarize, the advantages of nanotechnology in antiviral research include the
following
• 1) Promotes the delivery of water-insoluble drugs
• 2) Enhances the circulation time of drugs in vivo
• 3) Achieves co-delivery of drugs
20. Nanotechnology versus the virus
• 4) Improves drug utilization efficiency and reduce side effects through targeting
antibody modification
• 5) Protects DNA and mRNA vaccines, overcoming bottlenecks for in vivo
applications and
• 6) The physicochemical properties of nano-materials can also be employed
directly against viruses
21. Why nanotechnology?
• Currently, only symptomatic treatment is adopted for COVID-19 patients, and no
SARS-CoV-2 specific antiviral drugs or even vaccines are available.
• Also, the current methods employed for COVID-19 detection fail to identify the
mild or asymptomatic cases, which are capable of further spreading the disease
• Exploring nanotechnology-based approaches for combating COVID-19 will help
to overcome the limitations associated with conventional methods of viral disease
management.
• Many previous studies have reported the successful application of nanostructures
in developing virus detection systems and treatment modalities.
25. Personal protective equipment
• The virus is primarily transmitted between people via respiratory droplets when
coughing, sneezing, or in very close personal contact
• In this way, personal protective equipment (PPE) like gloves, eye protection,
gowns, and masks provide a barrier to prevent potential exposure to the virus.
• Fluid-resistant surgical filtering facemasks are designed to protect patients and
healthcare workers from the spread of infectious diseases.
• Using facemasks and other PPE with anti-viral effects could offer a more efficient
alternative.
26. Personal protective equipment
• It is suggested that synthesizing of ACE2 coated/embedded nanoflowers or
quantum dots to produce chewing gums, nose filters, and self-protective tools
like masks, gloves, and clothes
Angiotensin-converting enzyme 2 (ACE2)
27. Surface Coatings
• Nanomaterials-based coatings are currently used for several applications, and
different products are now available
• Particularly from metallic elements such as silver, bismuth, copper, or titanium
• Also, nanostructured surfaces can physically reduce the attachment of pathogens
and even disrupt the structure of the pathogens due to the nanoscale topography
organization
• Nanomaterials can be embedded in paints or coatings for medical
instrumentation, walls, and other highly-touched surfaces, such as doorknobs,
handrails, etc.
• For reducing the presence and viability of viruses and other pathogens
28. Disinfectants and Sanitizing Procedures
• To overcome the various strategies have been used to reduce infections by using
different disinfectent.
• The disinfectants are chemical substances applied on the surface to kill or inhibit
microorganisms.
• The various chemical compounds such as alcohols, quaternary ammonium cation,
aldehydes, oxidizing agents such as sodium hypochlorite, hydrogen peroxides,
iodine etc. have been used as disinfectant effectively.
• However, these compounds are suffered from various constraints such as
harmfulness, corrosive nature and bacterial resistance.
33. Disinfectants and Sanitizing Procedures
• Disinfectants with silver salts are currently used, as silver is deemed safe for
sanitizing purposes.
• In hospitals and other healthcare-related facilities, sanitizing with
nanotechnology-based products could decrease the viral presence on highly-
touched surfaces and maintain them virus-free for longer, including the SARS-
Cov-2 virus
34. Biosensors
• A biosensor is a device that combines a sensitive biological recognition
component and a physical transducer to detect analytes within solutions and
bodily fluids.
• Biosensors typically consist of three parts:
1. A bio-receptor (nucleic acids, antibody, enzyme, etc.),
2. Transducer (magnetic resonance, electrochemical, optical, electrical, thermal),
and
3. Electronic system/signal processing.
35. • The high specific surface interaction of the nanobiosensor with the bioanalyte
becomes highly efficient
• Thanks to the extremely large surface/volume ratio, which enables the
immobilization of an enhanced amount of bioreceptor units.
• , Up to now, there is only one nanobiosensor for SARS-CoV detection, FET-based
immunosensor, developed by Ishikawa and coworkers in 2009
• Where the antigen-antibody binding generates a change in conductance,
correlated to the virus concentration.
• The biomarker used for SARS-CoV detection is the virus antigen nucleocapsid
protein (N-protein), the most abundant protein in coronaviruses.
41. Blocking viral entry into the host cell
• The first step of the viral infection cycle involves the binding of the virus to the
host via cell surface receptors.
• Blocking the entry of viruses has been found to be a successful anti-viral strategy
in many viral infections
• By virtue of their properties, nanostructures are suitable to competitively bind and
inhibit viral entry into cells.
• Some nano-based approaches are targeted to binding the virus particles directly,
preventing them from approaching the host cell in the first place.
• For instance, carbon quantum dots were found to interact with the S protein of
human coronavirus (HCoV-229E strain), preventing the viral protein interaction
with the host cells.
42.
43. Inhibiting viral replication
• Once the virus enters the cell, it hijacks the cellular biochemical machinery to produce
more copies of itself.
• If the virus is able to successfully execute the second step of the infection cycle, it is
able to spread in the body and cause infection.
• Thus, therapeutic strategies targeting this step are extremely essential to contain the
infection.
• Nanostructures have mainly been utilized as carriers to deliver the anti-viral molecules
• However, recently a number of nanoparticles are shown to intrinsically inhibit viral
replication,
• such as Ag2S nanoclusters, which were reported to exert an inhibitory effect on
coronavirus replication, thereby preventing the budding of new viral particles from the
host cell.
46. Vehicle or cargo
• Drug delivery via Nano carriers helps to overcome several challenges associated
with the traditional method of antiviral drug administration.
• Poor bioavailability, susceptibility to in vivo degradation of drug, systemic toxicity,
and short half-life in the body are some of the drawbacks associated with antiviral
therapeutics
• However, Nano-delivery systems resolve these issues and enable higher
bioavailability, reduction in effective and drug dosage,
• it also offers lower toxicity, protection from degradation, improved half-life in
circulation and ability to cross the biological barriers to target viral infection in
sheltered body sites
49. NANOTECHNOLOGY OFFERS OPPORTUNITIES IN
VACCINE DESIGN
• Nanoparticles and viruses operate at the same size scale;
• Therefore, nanoparticles have an ability to enter cells to enable expression of
antigens from delivered nucleic acids (mRNA and DNA vaccines) OR
• Directly target immune cells for delivery of antigens (subunit vaccines).
• Lipid nanoparticles are mostly used for transport of nano-drugs and then thier
expression is controlled
51. NANOTECHNOLOGY OFFERS OPPORTUNITIES IN
VACCINE DESIGN
• On 18 November 2020, BioNtech and Pfizer announced the final results of their
COVID-19 vaccine phase 3 clinical trial
• These are the first messenger RNA (mRNA)-based vaccines hitting clinical use.
• This new class of DNA- and RNA-based vaccines deliver the genetic sequence of
specific viral proteins to the host cells using nanotechnology platforms.
52.
53.
54. Use in Nanomedicine
• Nanomaterials are widely used in dierent healthcare-related applications, such as
sanitizers, diagnosis, imaging tools, wound dressing, wearable devices, anticancer
therapies, pharmaceuticals,
• drug delivery, vaccines, diagnosis techniques, and implants, among others
• The global consumption for healthcare-related nanotechnology is expected to be
over 50 tons, just for silver nanoparticles, in 2020
• Antiviral nanomaterials are typically smaller than most viral particles, such as the
SARS-Cov-2 viral particle, which has an average size of 120 nm.
• Therefore, nanomaterials can interact with the whole viral particle or with the
surface proteins and other structural components, leading to the inactivation of
virus
55. Preclinical Studies, In Vitro and In Vivo
• The antiviral activity of nanomaterials against multiple viral families has been
studied in a wide diversity of reports.
• Studies in vitro show that silver nanoparticles (AgNPs) inactivate dierent types of
viruses, such as HIV-1, monkeypox virus, hepatitis B, Tacaribe virus, and the Rift
Valley fever virus
• Current literature suggests that nanomaterials may also eectively inactivate the
SARS-Cov-2 virus particles, as nanomaterials have been used for inhibiting other
viruses from the Coronaviridae family
56. Mechanisms of Action of Antiviral Nanomaterials
Antiviral activity of
nanoparticle
Direct activity Indirect activity
57. Mechanisms of Action of Antiviral Nanomaterials
• Nanomaterials with indirect activity do not inhibit the viruses by themselves
• Instead, they improve the activity of the antiviral treatments, and are used for
transport, stability, and enhanced bioavailability, among others.
• Moreover, nanomaterials can also induce an immune response for generating
short or long-term immunity
• In contrast, nanomaterials with direct activity act as the active compound,
because they inactivate the viruses by themselves, usually by altering the viral
structure or its genetic material
• Moreover, nanomaterials display other properties of clinical interest, such as
enhanced chemical reactivity and biocompatibility, controlled drug release, and
customizable target specificity
Hinweis der Redaktion
Fig. 2 Schematic representation of possible blocking of COVID-19 entering into the host at first step by ACE-2 coated nanoflowers and quantum dots. Respiratory masks, nasal filters, clothes, and chewing gums can be impregnated with functional ACE2-coated nanoflowers or quantum dots. Reprinted with permission from