Virus & Anti-Virals Flashcards
When R naught (epidemic reproductive rate) ____ 1, epidemic is sustained
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Most acute respiratory diseases are caused by…
viruses
small, +SS RNA, non-enveloped virus that causes common cold; hard to develop a vaccine due to >100 serotypes; can exacerbate chronic lung diseases
Rhinovirus
Pleiomorphic, -ssRNA, enveloped, highly contagious virus that can cause ARI with prodromal stage preceding rash; a good vaccine is available
Measles
What virus causes Koplik’s spots (mouth spots) before rash appears on the body?
Measles
Rare but what fatal degenerative disease of CNS (deterioration and seizures) can occur 7-10 years after measles infection?
SSPE
What viruses are on Exam 2? (5)
Rhinovirus Measles RSV Influenza Corona/SARS
3 high-yield respiratory viruses
RSV (humans only)
Influenza (A-zoonotic; B-humans)
corona/SARS (zoonotic)
-ss RNA, non-segmented, enveloped virus that is seasonal and causes lower airway disease (bronchiolitis) mostly in infants and elders; limited anti-virals and no vaccine
RSV
RSV has a single serotype with _____ antigentic groups
two (A & B)
Malaria kills the most children under 1 year old globally, and #2 goes to…
RSV
What percent of infants experience RSV by 3 years of age?
100%
What can possibly lower rates of RSV infection and disease?
Breast feeding and maternal antibody
lower tract diseases caused by RSV is usually ______ which is occlusion of small airways due to mucus and inflammatory materials
Bronchiolitis
Treatment for RSV
Supportive care; non-specific anti-viral; passive anti-RSV antibody
What are virulence factors of RSV?
Attachment & Entry: binds to host TLR4 receptor
- Glycoprotein G (Groups A & B based on different glycoprotein G)
- Fusion protein F
Viral pathogenesis that results in multiple cell fusion of infected and uninfected cells
Syncytium
Since RSV has -ssRNA, what does it must carry with it to replicate in the host?
RNA-dependent RNA polymerase (-ssRNA to +ssRNA)
RNA virus with RdRp activity; types based on NP and M sequences
Influenza A/B
Influenza virus infection often coincides with bacterial superinfection: which bacteria are most common
Staph. aureus
Strep pneumo
T/F: Complications of influenza virus infection include both pulmonary and non-pulmonary
True
What influenza type affects both humans & animals (zoonotic), affect all age groups, and cause more severe illness?
Type A (from birds/swine to humans)
- zoonotic increases pandemic potential
What influenza type affects only humans, affect children, and cause milder illness?
Type B
Influenza nomenclature are based on
Virus Subtype: (H#N#)
- Hemagglutinin (HA)
- Neuraminidase (NA)
What are the functions of virus surface structures found on Influenza viruses?
- HA: glycoprotein on virus that binds to the host cell’s sialic acid receptor
- NA: cleaves the sialic acid receptor, freeing the virus from the host cell
- M2 ion channel: maintains p H across viral envelop during cell entry
What virus surface structures are on Influenza Type A?
HA, NA, M2 ion channel
What virus surface structures are on Influenza Type B?
HA, NA
involves the accumulation of a series of minor genetic mutations, resulting in amino acid substitutions; prevents binding of antibodies induced by previous flu infection/vaccination
Antigenic drift
involves reassortment (“mixing”) of viral genes in Influenza Type A viruses, resulting in new H/N combinations; responsible for pandemics
Antigenic shift
Antigenic shift can occur between different types of influenza (A, B and C) (True or False)
False: Type A only can experience antigenic shift
Influenza vaccines induce antibodies to
HA and NA
What is the virus responsible for COVID-19?
SARS-CoV-2 (from bat to civet to humans)
What is the structure of coronavirus?
+ssRNA, enveloped, non-segmented virus
- RNA is packaged in a coiled structure made of N (nucleocapsid) proteins
What is the receptor for SARS-COoV-2 for entry into host cells?
ACE2
- protruding viral spike of coronavirus binds ACE2 receptor
ACE2 receptors are expressed by what cells?
epithelial cells in ORAL, LUNG, intestines, kidney, blood vessels
- why coronavirus cause upper respiratory and lung-related symptoms
Patients with HTN and diabetes are at risk for severe clinical presentations of COVID-19 because
they often take ACE inhibitors, resulting in increased expression of ACE2 receptors
Drugs of choice to treat CMV by blocking viral DNA synthesis
Ciclovirs
- Ganciclovir
- Valganciclovir
MoA of Ganciclovir
Ganciclovir is a purine analog that mimics guanosine during viral DNA replication. It gets triphosphate added by viral and host cellular kinases.
Two Effects:
1) Ganciclovir-triphosphate competes with GTP for binding to polymerase
2) incorporates into DNA causing chain termination
MoR against Ganciclovir
mutations in CMV kinase or CMV DNA polymerase
Toxicities of Ganciclovir
- Myelosuppression
- thrombocytopenia
- neutropenia - Category C Pregnancy risk (both Gan & Val)
Why is Valganciclovir more effective than Ganciclovir?
Valganciclovir is the pro-drug version of ganciclovir, so metabolism activates it (as opposed to ganciclovir who gets inactivated)
Drugs of choice to treat Influenza by inhibiting M2 ion channels
Mantadines
- Amantadine
- Rimantadine
MoA of M2 inhibitors
Mantadines inhibit viral uncoating by blocking M2 proton pump which acidifies viral envelop to facilitate viral uncoating.
Drugs of choice to treat Influenza by inhibiting neuraminidase (NA)
Mivirs
- Oseltamivir
- Zanamivir
MoA of neuraminidase inhibitors
Mivirs inhibit viral release by blocking neuraminidase that cleaves sialic acid-hemagglutinin complex.
Which influenza medication is best to start within 1 day of symptoms, or else it becomes drastically less effective?
Oseltamivir
Why might neuraminidase inhibitors be preferred over M2 inhibitors when treating Influenza?
M2 blockers are exhibiting resistance
toxicity for Zanamivir
Since it’s inhaled: Bronchospasm (avoid in asthma or COPD patients)
What pregnancy risk category are NA inhibitors belong to?
C
Drug of choice to treat RSV by inhibiting viral RNA polymerase
Ribavirin
MoA of Ribavirin
Ribavirin is a purine analog that blocks RSV RNA synthesis. 3 Effects:
- Inhibits GTP synthesis acting as an analog
- Gets incorporated into RNA producing a defective RNA
- Inhibits RNA replication by stopping RNA polymerase
Potential drug interactions and toxicities for Ribavirin
- Hemolytic anemia
- cause oxidative damage - Nephrotoxicity
- cleared in kidneys; avoid in patients with kidney problems - Category X
- cause DNA damage
- long half-life to be cleared - Blocks activation of HIV drugs
Drug of choice to treat coronavirus by inhibiting viral RNA polymerase
Remdesivir
Remdesivir was originally developed to treat
ebola
MoA of Remdesivir
Remdesivir is an adenosine analog that terminates viral RNA polymerization
Toxicities of Remdesivir
- Hepatotoxicity
2. Avoid in patients with renal issues
