Viral infections and anti-viral drugs Flashcards
what are examples of common viral infections?
Common cold
Flu
Bronchitis
Pharyngitis
Herpes (coldsores)
Chickenpox
Shingles
Conjunctivitis
Gastroenteritis/ Norovirus
MMR (less common now, vaccination)
SARS-CoV-2 (COVID-19
what are the possible routes of transmission?
- airbrone/droplets - influenza, MMR
-contact via non-living surfaces - common cold, influenza
-faceal-oral - rotavirus, hepatitis A, poliovirus
-insect bites - dengue , west nile, yellow fever
contact with lesions - herpes simplex, varicella zoster
sexual contact - HIV, hepatitis B, herpes
blood - HIV, Hep B and c
blood and body fluids - ebola, epsteib- Barr
mother to child - HIV, rubella, zika
how are viruses classified ( virus classification)
- Genetic material
- Mode of replication
- Structure and symmetry of capsid
- Presence / absence of envelope
What is Baltimore classification and examples
Groups I-VII (Baltimore classification)
(I – dsDNA, II – ssDNA, III – dsRNA, IV – (+)ssRNA,
V – (-)ssRNA, VI – ssRNA-RT, VII – dsDNA-RT)
Group 1 - HSV -1
Group 2 - Parovirus
Group 3 - Rotavirus
Group 4 - SAR-CoV-2
group 5 - Rabies
Group 6 - HIV
group 7 - HBV
DNA viruses
Replicate in host nucleus
Normally not incorporated into host genome
Examples: herpes, varicella-zoster, adenovirus
RNA viruses
Replicate usually in cytoplasm
Reproduction depend on sense / antisense RNA
Examples: rotavirus, enterovirus, rhinovirus,
rubella virus, rabies virus
how is Baltimore classification
how the virus makes mRNA- they are grouped according to that
what are antiviral drugs and their targets?
Antiviral drugs target different stages in viral life cycles and replication:
Attachment/Entry/Fusion inhibitors: Prevent binding or entry/fusion of virus with host cell, e.g. targeting viral receptors
Uncoating inhibitors: Prevent uncoating of capsid
Nucleic acid synthesis inhibitors: Common examples are nucleoside/tide analogs that block new RNA or DNA synthesis. Others inhibit enzymes required (polymerases or reverse transcriptase). Large number of this category are reverse transcription inhibitors (e.g. for HIV – see Lecture 6 HIV)
Integrase inhibitors: Specifically for retroviruses that rely on host genome integration (e.g. HIV)
Protease inhibitors: Inhibit proteases commonly used for generating viral proteins for assembly of new virions
Release inhibitors: Prevent release of virus from host cell, such as antivirals used for influenza
Other non-direct methods include immune modulation
what are examples of antiviral drugs?
Entry inhibitors:
Nucleic acid synthesis inhibitors
Nucleoside/-tide reverse transcriptase inhibitors (NRTIs/NtRTIs))
Integrase inhibitors:
Protease inhibitors/Inhibitors viral assembly:
Exit/Release inhibitors:
Entry inhibitors:
Enfuvirtide or Maraviroc – inhibits HIV binding/fusion with cells
Nucleic acid synthesis inhibitors
Nucleotide/side analogues
Aciclovir - herpes viruses and VZV (nucleoside analog, inhibits HSV DNA polymerases); Ganciclovir – CMV disease
Ribavirin –life-threatening RSV and PIV infections
Sofosbuvir (HCV, NS5B Polymerase inhibitor)
Remdesivir (SARS-CoV-2, nucleotide prodrug)
Nucleoside/-tide reverse transcriptase inhibitors (NRTIs/NtRTIs))
Zidovudine (AZT) – HIV (nucleoside analog)
Tenofovir alafenamide – HIV
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz (HIV)
Integrase inhibitors:
e.g. Bictegravir (HIV)
Protease inhibitors/Inhibitors viral assembly:
e.g. Atazanavir (HIV)
Voxilapravir (HCV)
Exit/Release inhibitors:
Zanamivir (Relenza) and Oseltamivir (Tamiflu) – block neuraminidase on flu viruses
Others:
Amantadine/rimantadine antagonist M2 channel of virus, prevent viral shedding and replication (once used influenza)
Via immune system – IFN-a, vaccines
what group is present if it is an RNA
OH
what group will be present if it is DNA
H
what makes a structure nucleoside
without phosphate
what makes a structure nucelotide?
with phosphate
mono/di/triphosphate
explain nucleic acid synthesis?
To add new nucleotide need a free hydroxyl on 3’ end of growing strand and 5’ triphosphate group on incoming nucleotide
Polymerase adds incoming nucleotide, releasing pyrophosphate
In viral infection can be viral polymerase or reverse transcriptase
Nucleoside/tide Analogs as Anti-viral Drugs: MoA
ACV: In the cell, gains first phosphate via the viral HSV-1 TK (kinase). Then further 2 phosphates via host kinases to become triphosphate. Lacks 3’ OH for further chain growth – INHIBITION viral DNA polymerase
guanosine and aciclovir - acv
how is respiratory viral infections transmitted?
Transmission via droplets or contact with nasal secretions / saliva
how is respiratory viral infections transmitted?
Transmission via droplets or contact with nasal secretions / saliva
smaller droplet = more contagious
what are the immune defences + non-specific for respiratory viral infections?
Body has non-specific and immune defences:
Respiratory endothelial cells (ECs) covered thick glycocalyx & tracheobronchial mucus (traps viral particles)
Cilliated respiratory ECs move particles from lower to upper respiratory tract, then swallowed
Lung immune response
what are the main respiratory viruses? (4)
Influenza viruses - Elderly most at risk
Rhinoviruses / Coronaviruses*
Both cause common cold
Adults ~ 2-5 colds/yr, Children ~ 4-8 colds/yr
Respiratory syncytial viruses (RSVs)
Major cause of respiratory illness in children
~90% of children by age 2
Serious in elderly, leads to pneumonia / death
Parainfluenza viruses (PIVs)
Cause colds, croup, bronchitis and pneumonia
Can be life threatening in infants
what is the causes of common colds?
Cause: Most by rhinoviruses as well as some coronaviruses (15%), picornaviruses, influenza viruses, PIV, RSV and others.
Coronaviruses HCoV-OC43, -HKU1, -229E and –NL63 can cause mild, cold symptoms. MERS-CoV, SARS-CoV and SARS-CoV-2 can be severe (see next slide)
what is the symptoms of common cold?
Symptoms: fever (children), sore throat, runny nose, sneezing, nasal congestion. Can also have muscle ache, fatigue headache, malaise.
Symptoms due to viruses largely affecting URT (mainly nose and can be throat, larynx, sinuses).
what is the transmission route for common cold?
Transmission: Usually airborne droplets + contact with secretions and fomites.
what is the mechanism of common cold?
Mechanism: Depends on virus. e.g. rhinovirus – binds receptors on ciliated surface of nasal epithelial cells (e.g. ICAM1) followed by receptor-mediated endocytosis. Leads to pro-inflammatory response
how can you prevent common cold?
Prevention: Good hygiene, hand-washing, tissues (sneezing)
no vaccines
what is the treatment for common cold?
Treatment: symptomatic: analgesia & antipyretics. Possible other OTC options
what is SARS-CoV-2
(what is viral spike unit)
Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2
New coronavirus, related to SARS-CoV, first identified in Wuhan, China, Dec 2019
An enveloped, + sense, ssRNA virus (group IV)
Enters cells via Angiotensin Converting Enzyme 2 (ACE2 receptor) on host cells
ACE2 highly expressed in epithelium of lung + intestine, and lesser extent in other tissues e.g., liver & kidney
Spike protein on surface of the virus important for cell infection
Viral Spike (S) protein has 2 domains: S1 receptor binding domain (RBD), S2 mediates fusion of virus with host membrane
what is the mechanism of SARS-CoV-2
Virus enters host cell by 2 main mechanisms: early/cell surface or late/endocytosis
S protein (S1, RBD) binds to ACE2
Proteolytic cleavage between S1 and S2 by TMPRSS2 (when present) activates the S protein releasing S1 and allowing fusion via S2 and cell surface entry
In absence of TMPRSS2, following binding to ACE2, virus enters via endocytosis
Cleavage in S protein by Furin before exit can prime virus for entry to infect new cells
Several stages of these pathways are possible therapeutic targets
what is the symptoms of covid 19
what is long covid?
Symptoms of COVID-19: fever, persistent cough, loss of taste/smell*, fatigue, muscle ache, shortness of breath and others including GI symptoms –
* original ‘key’ symptoms. Later variants: headache, sore throat, blocked/runny nose, nausea/vomiting, loss appetite…
Symptoms can be mild to severe and many with the virus can be asymptomatic
Long COVID: wide range symptoms, e.g., fatigue, SOB, insomnia, muscle ache…
what is the transmission route of covid
Transmission: Droplets. Prodromal illness typically 2-10d. 1 of 7 coronaviruses that affect humans. Aerosols? Fomites?
