NTU VirusBom Eng

Historical context
People
Influenza A Deaths Case fatality
Pandemic Year infected
virus subtype (est.) rate
(approx)
500 million - 20 to 100
Spanish flu 1918–19 H1N1 >2.5%
1 billion million
Asian flu 1956-58 H2N2 2 million <0.1%
Hong Kong
1968–69 H3N2 1 million <0.1%
flu
5-15% (340
mainly A/H3N2, 250,000-
Seasonal flu Every year A/H1N1, and B
million - 1 <0.05%
500,000
billion) Virulence
SARS 2002/11- SARS-CoV 8,096 774 9.6%
03/7
Avian flu 2003-2009 H5N1 436 262 60%
2009 flu 2008/4 to Novel H1N1 ~0.5%
97,211 479
pandemic date Influenza
Ref: en.wikipedia.org/wiki NTU Nano-BioMEMS Group

The A, B, C, H and N of Bird Flu Viruses
Glycoprotein—hemagglutinin
A B C
8 genes
 Influenza viruses come in three
types: A, B and C. How any one virus
acquires its identification letter
depends on differences in the matrix
protein, nucleoprotein and response
of antibodies to a particular strain.
Influenza A is the most dangerous
for humans, influenza C is the least
dangerous.
Glycoprotein—neuraminidase
H&N
 The H stands for one of the 16 different hemagglutinin proteins contained in a virus
that allows it to penetrate a foreign body. The "N" stands for another protein in the
genetic make-up of a flu virus called neuraminidase, of which there currently exist
nine variations.
Ref: 1. www.fao.org/avianflu/en/alpha.html NTU Nano-BioMEMS Group
2. www.rajib.info/blog/tag/asian-flu
WHO Pandemic Alert Phases
Phase 1 No infections in humans are being caused by
viruses circulating in animals.
Phase 2 Animal flu virus causes infection in humans, and
is a potential pandemic threat.
Phase 3 Flu causes sporadic cases in people, but no significant
human-to-human transmission. H5N1
Phase 4 Human-to-human transmission and community-
level outbreaks.
Phase 5 Human-to-human transmission in at least two
countries. Strong signal pandemic imminent.
Phase 6 Virus spreads to another country in a different
region. Global pandemic under way. H1N1
Post-peak Post-peak: Pandemic activity appears to be
Post- decreasing though second wave possible. High rate of
pandemic Post-pandemic: activity returns to normal, infection
seasonal flu levels.
NTU Nano-BioMEMS Group

H5N1 Avian flu Infection Map

H1N1 flu Infection Map

Droplet Spread
 Influenza viruses are predominantly transmitted

from person to person via respiratory droplets
 The influenza virus can remain suspended in the
air in respiratory droplets for as long as 3 hours.
 The virus can survive for 24-48 hours on hard,
non-porous surfaces (i.e., telephone receivers,
computer keyboard, doorknob, kitchen
countertop, toys);
 8 hours on cloth, paper and tissue;
 and 5 minutes on hands.
Ref: Muir, P, "Treatment of Influenza. Essential CPE. Continuing Education from the NTU Nano-BioMEMS Group
Pharmaceutical Society of Australia," Paragon Printers, Australasia, ACT (2002).
The size comparison among viruses,
bacteria and fungi

Infection Control
People
Pandemic Year infected
Infection Control
(approx)
500 million -
Spanish flu 1918–19
1 billion
Mutation
Asian flu 1956-58
Hong Kong
1968–69
flu
Virulence
5-15% (340
Seasonal flu Every year million - 1
billion) High rate of
infection
SARS 2002/11- 8,096
03/7
Avian flu 2003-2009 436
2009 flu 2008/4 to
97,211
pandemic date
Screening Chemicals (I)：
Surface nanostructure design and chemical compound synthesis
for nanoscale virus
VirusBom

Surface structure of bacteria
O-Antigen
n n n n n n n n n n n n n
Outer membrane
LPS
Outer core
Inner core
P P P P P P P P P P P P P P P P P
Lipid A
Outer
leaflet
Inner leaflet
SmL
SmL
Peptidoglycan SmL
Inner
SmL
membrane SmL
SmL

Screening Chemicals (II)：
Surface nanostructure design and chemical compound synthesis
for microscale virus
VirusBom

The experimental results and data of
NTU - VirusBom
Influenza virus subtype H1N1
NTU – VirusBom can inhibit and disintegrate

1. Influenza virus subtype H1N1
TM
2. ( Tamiflu - Resistant ) virus subtype
H1N1 productive infection

The effectivity of VirusBom for influenza virus
subtype H1N1
30-300ppm
VirusBom (ppm) 0 3 10 30 100 300 1000 3000
Influenza + + +/- - - - CTX CTX

A/WSN/33 (H1N1)
+ + +/- - - - CTX CTX
Tamiflu resistant
H1N1 strain
(A/TW/066/09)
- - - - - - CTX CTX
control group
• Repeat for 4 times, CTX ( Cytotoxicity )
• The treatment of influenza virus subtype H1N1 by VirusBom at room temperature(25℃)
• MDCK cells are infected for 2 hrs at 37℃
0 ppm VirusBom
Madin-Darby Tamiflu-
canine kidney resistant
(MDCK) cell H1N1 strain
D+V
Light spot indicated that the

number of death MDCK cells
Influenza are much more than the same
A/WSN/33 cells in the left figure.
(H1N1)
D+V D+V:0 ppm VirusBom + Virus

Light spot indicated that the MDCK cell：40µm
are much more than the same NTU Nano-BioMEMS Group
cells in above figure.
3 ppm VirusBom
D+V

Influenza are much more than the same
A/WSN/33 cells in the left figure.
(H1N1)

Light spot indicated that the MDCK cell：40µm
10 ppm VirusBom
D+V

Influenza reduced in much more than
A/WSN/33 the same cells in the left
(H1N1) figure.
Light spot indicated that the MDCK cell ：40µm
100 ppm VirusBom
D+V

Influenza compared with the same cells
A/WSN/33 in the left figure reduced a lot.
(H1N1)

MDCK cell：40µm
compared with the same cells
in the above figure reduced a
lot.
1000 ppm VirusBom
D+V
Treating cells with 1000 ppm

VirusBom showed that the
Influenza cells is cytotoxic
A/WSN/33
(H1N1)
MDCK cell：40µm
Treating cells with 1000
ppm VirusBom showed
that the cells is cytotoxic NTU Nano-BioMEMS Group
Avian flu virus efficacy
Avian flu virus efficacy

75-600ppm
ANIMAL HEALTH
RESEARCH INSTITUTE
• Repeat for 4 times

• The treatment of avian flu virus by VirusBom for 30 mins at room temperature(25℃)
• MDCK cells are infected for 2 hrs at 37℃
Spraying VirusBom on the unwoven cloth
ANIMAL HEALTH
RESEARCH INSTITUTE

Avian influenza virus (H5N1 /H5N2) inhibition effect (Unit：ppm)
1-1 1-2 1-3 1-4 1-5 1-6 1-7 1-8
VirusBom 3000 1000 300 100 30 10 3 0
1 H5N2 CT CT - - + + + +
H5N1 CT CT - - + + + +
2-1 2-2 2-3 2-4 2-5 2-6 2-7 2-8
Compound 2
3000 1000 300 100 30 10 3 0
2
H5N2 CT - + + + + + +
H5N1 CT - + + + + + +
3-1 3-2 3-3 3-4 3-5 3-6 3-7 3-8
Ai represents virus inhibition effect; Compound 3
CT represents cell cytotoxicity; 3000 1000 300 100 30 10 3 0
3
H5N2 CT - + + + + + +
“-” The infection and proliferation H5N1 CT - + + + + + +
effect of virus was suppressed 4-1 4-2 4-3 4-4 4-5 4-6 4-7 4-8
“+” The infection and proliferation Compound 4
3000 1000 300 100 30 10 3 0
effects of virus wasn’t 4
H5N2 CT CT - + + + + +
suppressed
H5N1 CT - + + + + + +
5-1 5-2 5-3 5-4 5-5 5-6 5-7 5-8
Compound 5
3000 1000 300 100 30 10 3 0
5
H5N2 CT CT + + + + + +
H5N1 CT - + + + + + +
6-1 6-2 6-3 6-4 6-5 6-6 6-7 6-8
Compound 6
3000 1000 300 100 30 10 3 0
6
H5N2 + + + NTU+ Nano-BioMEMS
+ + Group
+ +
H5N1 + + + + + + + +
H5N1 + + + + + + + +
7-1 7-2 7-3 7-4 7-5 7-6 7-7 7-8
Compound 7
3000 1000 300 100 30 10 3 0
7
H5N2 + + + + + + + +
H5N1 - + + + + + + +
8-1 8-2 8-3 8-4 8-5 8-6 8-7 8-8
Compound 8
3000 1000 300 100 30 10 3 0
8
H5N2 + + + + + + + +
H5N1 + + + + ++ + + +
9-1 9-2 9-3 9-4 9-5 9-6 9-7 9-8
Compound 9
3000 1000 300 100 30 10 3 0
9
H5N2 增生 - - + + + + +
H5N1 - + + + + + + +
Ai represents virus inhibition effect;
CT represents cell cytotoxicity; 10-1 10-2 10-3 10-4 10-5 10-6 10-7 10-8
Compound 10
3000 1000 300 100 30 10 3 0
10
“-” The infection and proliferation H5N2 - - + + + + + +
effect of virus was suppressed H5N1 + + + + + + + +
“+” The infection and proliferation 11-1 11-2 11-3 11-4 11-5 11-6 11-7 11-8
effects of virus wasn’t Compound 11
3000 1000 300 100 30 10 3 0
suppressed 11
H5N2 - + + + + + + +
H5N1 + + + + + + + +
12-1 12-2 12-3 12-4 12-5 12-6 12-7 12-8

Compound 12
3000 1000 300 100 30 10 3 0
12
H5N2 + + + + + + + +
H5N1 + + + + + + + +
D-1 D-2 D -3 D -4 D -5 D -6 D -7 D -8
DMSO
3000 1000 300 100 30 10 3 0
D NTU Nano-BioMEMS Group
H5N2 + + + + + + + +
VirusBom Before treatment with VirusBom
Picture A: A single influenza A virus subtype H1N1 virion

A B
B C D E
C
D
A’ B’ C’ D’ E’
A’’ B’’ C’’ D’’ E’’

VirusBom After treatment with VirusBom(30ppm)
Picture B and C : The conditions that influenza A virus subtype H1N1 virion is treated with VirusBom.
The pictures show that virus particles are broken down.
A D
B C D
C
B
A’ B’ C’ D’

VirusBom After treatment with VirusBom(300ppm)
Picture B and C : The conditions that influenza A virus subtype H1N1 virion is treated with VirusBom.
The pictures show that virus particles are broken down.
A B E
C D E
D
C
B
A’ B’ C’ D’ E’
A’’ B’’ C’’ D’’ E’’

NTU - VirusBom 以下為金黃色葡萄球菌experiment 結果與數據
NTU - VirusBom inhibited the multiplication

of S. aureus

Inhibition of Staphylococcus aureus
VirusBom Unit：ppm
1-1 1-2 1-3 1-4 1-5 1-6
VirusBom 100 50 20 10 5 0
1
Staphylococcus aureus - - - + + +
2-1 2-2 2-3 2-4 2-5 2-6
2 Compound 2 100 50 20 10 5 0
Staphylococcus aureus - - - + + +
7-1 7-2 7-3 7-4 7-5
Compound 3
3 200 60 20 6 0
Staphylococcus aureus + + + + +
Gold nanoparticle 3-1 3-2 3-3 3-4 3-5 3-6 3-7
4 (AuNP) 1000 500 100 50 10 5 0
Staphylococcus aureus + + + + + + +
4-1 4-2 4-3 4-4 4-5 4-6 4-7
” - ” Proliferation of Staphylococcus AuNP-S－(CH2)12－SO3H
aureus was suppressed 5 1000 500 100 50 10 5 0
Staphylococcus aureus + + + + + + +
”+” Proliferation of Staphylococcus
5-1 5-2 5-3 5-4 5-5 5-6
aureus was not suppressed HS－(CH2)12－SO3H
6 100 50 20 10 5 0
Time of treatment is 2 hrs Staphylococcus aureus + + + + + +
6-1 6-2 6-3 6-4 6-5 6-6
HO－(CH2)12－SO3H
7 100 50 20 10 Nano-BioMEMS
NTU 5 0 Group
Staphylococcus aureus + + + + + +
VirusBom Before treatment with VirusBom
After treatment with VirusBom

VirusBom Distribution chart of viscosity force
25
Before treatment
After treatment
20 Fadhesion = 5.4 + 0.3nN
15
Counts
Fadhesion = 10.7 + 1.3 nN

10
0
0 2 4 6 8 10 12 14 16 18
Adhesion force (nN)
VirusBom can collapse the lipopolysaccharide(LPS) structure of S. aureus, so the
exposure and dispersed of inner membrane lipoprotein will increase the viscous force.

VirusBom can collapse the lipopolysaccharide(LPS) structure of S. aureus, so the
exposure and dispersed of inner membrane lipoprotein will increase the viscous force.
n n n n n n
P P P P P P P P P P

Functionalized
NTU Anti-
Experimental Results VirusBomTM Nanoparticles
SARS No.1
(FNPGS)
1. Influenza virus Proliferation was

subtype H1N1 suppressed : Proliferation was
2. TamifluTM 30 - 300 ppm not suppressed --
drug resistance to Cell toxicity assays : until 1000 ppm
Influenza virus H1N1 > 1000 ppm
With lipid
envelope
Proliferation was Proliferation was
Proliferation was
1. Avian influenza suppressed : suppressed :
suppressed :
Nanoscale Virus virus subtype H5N1 > 300 ppm > 3000 ppm
2. Avian influenza 100 - 300 ppm
Cell toxicity FNPGS is not toxic
virus subtype H5N2 Cell toxicity assays :
assays : for cell
> 1000 ppm
> 1000 ppm < 3000 ppm
Proliferation of
Without Proliferation was
Enterovirus 71 was
lipid Enterovirus 71 suppressed : --
not suppressed
envelope 30 -1000 ppm
until 1000 ppm
Proliferation of Proliferation of
Proliferation of S.
Micro S. aureus was S. aureus was
scale
Bacteria S. aureus aureus was suppressed:
not suppressed not suppressed
> 20 ppm
until 1000 ppm until 1000 ppm
“--” The experiment is proceeding NTU Nano-BioMEMS Group

NTU - VirusBom
Conclusion
 The experience which NTU nano-bio research group got during SARS infection（
epidemic prevention is regarded as a war ）
 The first class team must have social responsibility.
 The cooperation with teams consist of different research field could make wonders.
 The technology of virus nanostructures dynamics by applying atomic force
microscopy in P2 laboratory is keeping top of world.
 The new derivatives and applications of NTU Anti-SARS No.1
 The synthesis of original organic chemical compound for mass production.
 The fundamental research, technology transfer and industry-education cooperation
can go in parallel.
 In the past 6 years, because of the spreads and harm by global epidemic
 To improve the applications in short range and long range base on the basic
research spirit  lead compound、spray、hand cleanser.

The natural reservoir of influenza A viruses and the
interspecies transfer of the virus
H1N1
H5N1,
H5N2
Ref: Erin M. Sorrell, Hongquan Wan, Yonas Araya, Haichen Song, and Daniel R. Perez. Minimal molecular
constraints for respiratory droplet transmission of an avian-human H9N2 influenza A virus. Proceedings of NTU Nano-BioMEMS Group
the National Academy of Sciences, 2009; DOI: 10.1073/pnas.0900877106
NTU - VirusBom
NTU VirusBom
Application

© 2009 國立台灣大學
Virus and bacteria are broken down with compounds
Influenza virus H1N1

۩ Anti- TamifluTM influenza virus H1N1
۩ Avian influenza virus H5N2
۩ Avian influenza virus H5N1
Staphylococcus aureus
Enterovirus 71

Illustration of H1N1
H1N1 flu is an acute respiratory disease, which often cause fever, headache,
muscular pain, tiredness, snivel and cough.
New cases of anti-Tamiflu Influenza H1N1 had been reported by Denmark,
Japan and Hong Kong. Clinician announce if the anti- drug strains were
appeared, 5 fold mortality would happened on chronic disease patients who
infected with new flu. Base on report from WHO, new flu infection had
reached 100k cases and outbreak rapidly, and it had been spread for 100
countries.

Summary
۩ More than 3500 cases were confirmed with 5 died in Canada. （6/14）
۩ New flu is spreading in Hong Kong and reached 444 cases. （6/25）
۩ CDC estimates more than 1M cases might infect new flu in US. （6/26）
۩ 7500 cases were reported in UK. The official announced 100 k cases might happened daily
before end of August.
۩ All 27 EU members had became affected area of new flu. （7/2）
۩ New flu is spreading in Beijing.（7/2）
۩ New flu is spreading in Taiwan and reached 444 cases.（7/2）
۩ New flu is spreading in South Korea and reached 241 cases. （7/3）
۩ New flu is spreading in Brazil and reached 241 cases. （7/3）
۩1710 cases were reported in Thailand and 6 died. （7/4）
۩ 1055cases were reported in Singapore and 591people are infected in local.（7/6）
source：Internet

The danger of H1N1
۩ Influenza viruses H1N1 are predominantly transmitted from person
to person via respiratory droplets and close contact. The spread speed
and range of influenza viruses H1N1 is very fast and wide once its
outbreaks occurred. Further more, the complication with H1N1 is
series especially for the bacterial pneumonia and viral pneumonia.
People who have severe symptoms and death from the outbreaks are
elderly and patients with with cardiac, renal, anemia
immunosuppression.
VirusBom can disintegrate H1N1 virus
۩ The known H1N1 virus which can be disintegrated by VirusBom are
۩ Influenza A virus subtype H1N1
۩ Influenza A virus subtype H1N1(Tamiflu-resistant strains)
NTU - VirusBom
Avian Influenza
What is Avian Influenza?
۩ Avian influenza mainly infects among birds, and its highly infectivity is easy
to cause death. The outbreaks of avian influenza H5N1 occurred across eight
countries in Asia form 2003 to 2004, and at least 100 million infected poultry
have been killed by it. This outbreaks have been controlled until March 2004.
In June 2004 a
new outbreak of H5N1 surfaced and spread to many countries and regions
in Asia. Between 2005 and 2006, the cases of avian influenza H5N1 have
been reported in Europe, Africa and the Middle East.
The danger of Avian Influenza for humans
۩ The major parents are younger and older age group, and most of them are
direct or close contact with infected poultry or contaminated environment. In
general, patients who catch avian influenza at infancy usually have symptoms
that include high fever (more than 38 degree C), sore throat, cough, muscle aches,
headache. Part of them might have the vomiting, diarrhea and stomachache
problems, and they may also have breathing difficulty and lower respiratory tract
infections after few days. According to the lived experience, many parients who
have series clinical symptoms will become worst even cause death with 50%
fatality rate. Avian Influenza will spread among humans, because there’s no
immune antibodies in the human body.
VirusBom can disintegrate avian influenza
۩ The known H1N1 virus which can be disintegrated efficiently by
VirusBom are
۩ Avian influenza subtype H5N2
۩ Avian influenza subtype H5N1
NTU - VirusBom
Staphylococcus aureus is a very common bacterica.
Staphylococcus aureus is not only the major pathogen on the food industry but also the
origin of chronic nosocomial infection in hospitals.
Staphylococcus aureus causes the surgical site infection or systematic infection especially
for patients on hemodialysis sick with dermatosis and immunocompromised patients.
Staphylococcus aureus is the highest and quickest infection in large teaching hospitals.
Staphylococcus aureus infection
Staphylococcus aureus infects through human-to-human contact or items
transportation form original carrier.
Staphylococcus aureus is common symptom is the skin infection (for example, cellulitis,
impetigo, breast infection). It causes bacteremia especially for wound infection or drug
abuse.
Staphylococcus aureus is also the pathogen about food and gut, its incubation period
is very short，it will be taken with a disease in 1-8 hours, its complications is Toxic
Shock Syndromed, patients will occur pyrexia, hypotension, rash and peeling of skin
and influence other organs.
NTU - VirusBom
Enterovirus 71
Enterovirus 71
۩ Enterovirus 71 was infected by enterovirus and it’s major symptoms

were hand, foot and mouth disease or herpangina.
۩ According to over 500 clinical monitoring systems throughout the
country, epidemic situation of Enterovirus 71 was starting in Marth
every year, and most serious between May and June.The situation was
to slow down after June but got another epidemic in September.
۩ The most Enterovirus 71 sickers were children, especially under 5
years old. To the severe cases, amounts of children is almost 90% ; To
the deadly cases, amounts of children is the most one.
Enterovirus 71 risk
۩ Enterovirus 71 cause nervous system complications easily, and it’s a global

scatter.
۩ Children was the high-risk group of enteroviruses Infection with Severe
Complication and death, and the deadly rate of severe was 3.8 to 25.7%.
۩ From 2009.1.1 to 2009.5.31, medical institutions were informed of 56 cases of
severe Enterovirus 71 infection cases in the whole country. 21 cases of post-
judgment after identifying, and two of them were died. There were 220 case
reports and 173 cases of confirmed (8 cases of death) until last year (2008).
۩ According to clinical monitoring systems (data was up to may 30, 2009 (the first
22 weeks)) : the epidemic situation of enterovirus was more serious recently.
Enterovirus 71 method of infection
Enterovirus 71 spread mainly through the gastrointestinal tract (fecal -

oral, water or food contamination) or respiratory (droplets, coughing or
sneezing) and through contact with a patient can also be liquid blisters
the skin and become infected. in a few days prior to the onset of throat
and faeces can be part of the virus is identified, at this time that is
highly infectious, usually after within one week onset of the most highly
infectious; and sustainable by patients with intestinal release of viruses,
as long as 8-12 weeks years.

NTU VirusBom Eng

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Historical context

Ref: en.wikipedia.org/wiki NTU Nano-BioMEMS Group

NTU Nano-BioMEMS Group

NTU Nano-BioMEMS Group

NTU Nano-BioMEMS Group

 Influenza viruses are predominantly transmitted

NTU Nano-BioMEMS Group

NTU Nano-BioMEMS Group

NTU Nano-BioMEMS Group

NTU Nano-BioMEMS Group

NTU – VirusBom can inhibit and disintegrate

NTU Nano-BioMEMS Group

VirusBom (ppm) 0 3 10 30 100 300 1000 3000

Influenza + + +/- - - - CTX CTX

Light spot indicated that the

D+V D+V:0 ppm VirusBom + Virus

Light spot indicated that the

D+V D+V:3 ppm VirusBom + Virus

Light spot indicated that the

Light spot indicated that the

D+V D+V:100 ppm VirusBom + Virus

Treating cells with 1000 ppm

Avian flu virus efficacy

• Repeat for 4 times

NTU Nano-BioMEMS Group

12-1 12-2 12-3 12-4 12-5 12-6 12-7 12-8

Picture A: A single influenza A virus subtype H1N1 virion

A’’ B’’ C’’ D’’ E’’

NTU Nano-BioMEMS Group

NTU Nano-BioMEMS Group

A’’ B’’ C’’ D’’ E’’

NTU Nano-BioMEMS Group

NTU - VirusBom inhibited the multiplication

NTU Nano-BioMEMS Group

7-1 7-2 7-3 7-4 7-5

Gold nanoparticle 3-1 3-2 3-3 3-4 3-5 3-6 3-7

4 (AuNP) 1000 500 100 50 10 5 0

After treatment with VirusBom

NTU Nano-BioMEMS Group

Fadhesion = 10.7 + 1.3 nN

NTU Nano-BioMEMS Group

NTU Nano-BioMEMS Group

1. Influenza virus Proliferation was

“--” The experiment is proceeding NTU Nano-BioMEMS Group

NTU Nano-BioMEMS Group

NTU Nano-BioMEMS Group

Influenza virus H1N1

۩ Avian influenza virus H5N2

۩ Avian influenza virus H5N1

NTU Nano-BioMEMS Group

muscular pain, tiredness, snivel and cough.

New cases of anti-Tamiflu Influenza H1N1 had been reported by Denmark,

appeared, 5 fold mortality would happened on chronic disease patients who

NTU Nano-BioMEMS Group

NTU Nano-BioMEMS Group

outbreaks occurred. Further more, the complication with H1N1 is

series especially for the bacterial pneumonia and viral pneumonia.

elderly and patients with with cardiac, renal, anemia

۩ Influenza A virus subtype H1N1

۩ Influenza A virus subtype H1N1(Tamiflu-resistant strains)

been reported in Europe, Africa and the Middle East.

۩ Avian influenza subtype H5N2

۩ Avian influenza subtype H5N1