Drug Repurposing Commonly Against Dengue Virus Capsid and ...
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![Page 1: Obligate intracellular parasite Small: 10-100 nm Nucleic acid genome DNA or RNA single- or double-stranded Protein capsid Lipid envelope.](https://reader030.fdocuments.in/reader030/viewer/2022032723/56649d0a5503460f949dc4a6/html5/thumbnails/1.jpg)
Obligate intracellular parasite Small: 10-100 nm Nucleic acid genome
DNA or RNA single- or double-stranded
Protein capsid Lipid envelope for some animal viruses
What is a virus?
Enveloped RNA virus
Naked DNA virus
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No metabolism outside a host cell Requires host nucleotides, amino acids, enzymes, energy
Genome directs host cell to make virus proteins Copies of genome + proteins assembled into new viruses
Viruses don’t divide, they replicate
+
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Is a virus a cell?
size
membrane
metabolism
composition
genetic material
virusescells
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Is a virus alive?
living non-living
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1. Attachment
2. Entry
3. Uncoating
4. Nucleic acid replication & protein synthesis
5. Assembly
6. Exit
Virus replication
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Virus protein binds membrane receptor Determines host range
Attachment
HPV(naked)
influenza virus(enveloped)
virus “spike” protein
virus “spike”protein
host cellreceptor
host cellreceptor
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Naked virus usually enters by endocytosis Enveloped virus usually enters by fusion
Entry
influenza virus(enveloped)
HPV(naked)
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Genome released from capsid proteins For naked virus, must also escape vesicle
Uncoating
HPV(naked)
influenza virus(enveloped)
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Genome replicated Viral proteins synthesized by host ribosomes
Replication
HPV(naked)
influenza virus(enveloped)
envelope proteinsinserted into membrane
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Viral proteins self-assemble into capsid Viral proteins package genome
Assembly
HPV(naked)
influenza virus(enveloped)
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Naked virus lyses cell Enveloped virus “buds” out, taking membrane as envelope
Exit
influenza virus(enveloped)
HPV(naked)
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Useful drugs must be selectively toxic: Kill the disease-causing organism Leave host cells unharmed
Antibiotics exploit differences between proks and euks: Unique cell wall carbohydrates in bacteria Unique structures of bacterial ribosomes Prokaryotic RNA polymerase
Viruses replicate in our own cells, using our own machinery
Antiviral drugs
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Acyclovir Herpes family: herpes, chicken pox, shingles, etc. Blocks viral DNA synthesis Reduces duration and severity of infection
Antiviral drugs
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“Relenza” and relatives Influenza virus Prevents new budding viruses from
detaching and spreading Reduces duration of flu by ~2 days
Antiviral drugs
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HAART “cocktail” HIV virus Blocks 2 key viral enzymes Extends life Improves quality of life
Antiviral drugs
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Our best weapon against viruses so far
Vaccination
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Inject safe form of viral proteins (antigens) Immune system produces antibodies and memory cells Fast response to actual virus prevents disease
Vaccination
“flu shot”(killed virus)
Y YY
Y
anti-fluantibodies
anti
body p
roduct
ion →
time →≈10 days 1-2 days
infection withactual flu virus
Y YY
Y
YYY
Y YY
Y
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Smallpox killed 300,000,000 in the 20th century
Edward Jenner developed vaccination in 1796
Vaccination allowed eradication of the disease Last case in 1977
Smallpox vaccination
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Polio should be the next disease to be eradicated
2010968 cases
Vaccination
1988350,000 cases
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Vaccine development difficult for some diseases (e.g., HIV) Difficulty of universal distribution Side effects, real and imagined Public resistance to vaccination Sensational, irresponsible media coverage Not an economic priority for many drug companies Regulatory issues: >10 years to license a new vaccine
Vaccine issues
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Mutation New influenza virus strains (need a shot every year) “Swine flu” or “Bird flu” becomes human flu pandemic?
Species jump HIV probably evolved from a chimpanzee virus SARS coronavirus may have started as a bat virus
Spread from isolated population Public attention/media
Emerging viral diseases