Antivirals Flashcards
What is a virus
infectious, obligate intracellular parasite
aka can only replicate inside another cell
NOT CELLS
dependant on host cells to synthesise progeny virus particles
How do most viruses survive?
the viral genome is packaged inside particles
the genome contains all the information required to initiate and complete an infection within a susceptible and permissive cell
all successful viruses establish themselves in a host population
susceptible vs permissive
a susceptible cell has a functional receptor for a given virus (aka the virus can enter)
a permissive cell has the capacity to support virus replication
MUST BE BOTH SUSCEPTIBLE AND PERMISSIVE
a resistant cell means it is not susceptible, but not necessarily not permissive
Viral structure
nucleic acid surrounded by a capsid
+/- an envelope full of protiens surrounding the nucleocapsid
the genome of a virus can take many different forms such as
linear double strand DNA, circular ds DNA, circular ss DNA, ds RNA, + ss RNA, - ss RNA
negative sense RNA is complimentary to mRNA, and positive sense RNA is the same as mRNA and can be replicated directly
this genome does not code for membrane proteins or enzymes, but instead non-functional proteins that must be cleaved to make them functional
viral replication
the virus attaches to a cell, usually interacting via receptors
penetrates the membrane and injects nucleic acid into the cell
using the host machinery, the viral nucleic acid replicates
uses the host machinery to make non-functional proteins that are then cleaved by proteases to make the structural proteins and enzymes
the viral nucleic acids are packaged in viral proteins and burst from the cell, may or may not destroy the host
SARS-CoV-2 virus
severe acute respiratory syndrome
family: coronaviridae
enveloped virus, linear + ss RNA
receptor: angiotensin converting enzyme 2 (ACE2), respiratory epithelial cells
can enter to 2 ways: plasma membrane fusion, or endosomal membrane fusion. (interacts with ACE2, then injecting through the named membrane)
does not need to enter the nucleus to replicate, because it is compatible with mRNA.
transcription done by RNA dependant RNA polymerase
COVID-19 symptoms
incubation time: 2-14 days after contact, and generally take 5-6 days for symptoms to begin
fever, dry cough, fatigue, sputum production
first infects the upper respiratory system and inflames the lungs, then gets into the blood to infect other organs
main risk factors of severe COVID
over 75 years of age
obesity
cancer and treated with chemotherapy
immunocompromised
organ transplant
severe chronic diseases such as asthma, diabetes, end stage kidney disease
systemic corticosteroids in people with COVID-19
only for those who require respiratory support (or for other indications) like mechanical ventilation or supplemental oxygen
paxlovid
nirmatrelvir + ritonavir
nirmatrelivir inhibits the protease
ritonavir inhibits the metabolism of nirmatrelvir
Dose: 300mg nirmatrelvir and 100mg of ritonavir orally bid for 5 days (reduce for moderate renal impairment)
given as soon as possible after diagnosis, and within 5 days of symptom onset
indicated for those at risk of severe disease and are: unvaccinated, vaccinated but immunocompromised meaning it is likely to be unprotected, vaccinated adults at high risk (eg older 75, or 65 with additional risks)
limits: only for those with currently mild but risk of severe disease, not those with currently severe. not for prophylaxis for the prevention of COVID-19. not for paediatric patients. not for use over 5 days)
Remdesivir
pro-drug
IV administration
inhibits rna dependant rna polymerase
Indications: COVID-19 positive, but do not require oxygen with less than or equal to 7 days since symptom onset, for unvaccinated or immunocompromised patients at risk of progressing to severe infection. Dose: 200mg, 2 x 100mg
hospitalised patients older than 12 with pneumonia requiring supplemental oxygen. Dose: 200mg, 4 x 100mg
Tocilizumab
IV
recombinant anti-IL-6 receptor IgG antibody
covid causes high levels of Il-6, which could cause a “cytokine” storm
Indicated: ICU admission with severe pneumonia and requiring respiratory support, or recently hospitalised with significantly increased inflammation markers and requiring non-invasive ventilation or high-flow oxygen
single dose of 8mg/kg to a maximum of 800mg
Special populations and COVID-19
Pregnant women are no more or less likely to have a covid infection than the general population. prednisolone and hydrocortisone are preferred corticosteroids over dexamethasone due to crossing the placenta less. oral paxlovid is okay to give, and iv remdesivir has no evidence of causing harm, but its only based off of a case-study
children have lower risks of developing severe COVID than adults. vaccination is the safest option, as theres very little reseach on the effects in the paediatric population
Influenza structure
family: Orthomyxoviridae
enveloped virion with - ss RNA (aka requires the nucleus to replicate)
in the envelope there are two major proteins: haemagglutinin and neuraminidase
haemagglutinin binds to the sialic acid receptors in the human cells in the respiratory tract, neuraminidase cleaves the neuraminic acid molecules in infected cells
when finished replicating using the nucleus, the virus buds from the cell membrane, however this causes the sialic acid receptors to bind in again, requiring them to be cleaved
Influenza as a disease
spread by aerosol droplets, respiratory droplets, or contact with contaminated surfaces
incubation period: 1-5 days, infectious period: 5-7 days
symptoms: fever, headache, fatigue, cough, sore throat, runny or congested nose, aches, diarrhoea and vomiting (children, not as often adults)
antigen drift and shift
genetic changes to the virus
drift: minor changes in the haemagglutinin and neuraminidase antigens (happens annually)
shift: major change (30% or more) in haemagglutinin and/or neuraminidase antigens, creating a “new virus” that can start an epidemic or pandemic
compilations of influenza infection
respiratory is most common. eg pneumonia, croup, exasperation of COPD, bronchitis, otitis media
cardiovascular issues are not uncommon eg myocarditis and pericarditis
muscular: rhabdomyositis and rhabdomyolysis
neurological: Reye’s syndrome, encephalitis, transverse myelitis
systemic: toxic shock syndrome, sudden death
How to prevent the spread of influenza
VACCINATE (the exact virus changes from year to year, and therefore high risk people should
wash hands
cover nose and mouth when sneezing and coughing
don’t touch face
isolate when sick and avoid others who are sick
people at high risk of influenza complications
over 65
resident of chronic-care facilities
people with chronic diseases
pregnant people in the 2nd or 3rd trimester during flu season
treatment of influenza
rest, fluid intake, paracetamol, antivirals
NOT ANTIBIOTICS
neuraminidase inhibitors
zanamivir (powder for inhalation) and oseltamivir (oral preparation)
use within 48 (ideally 12) hours of symptoms starting up
exceptions can be made for critically ill people, and those who have been hospitalised due to the influenza
prevents the sialic acid receptors from being cleft, therefore the virion cannot be released from the host cell
side effects of zanamivir: allergic reaction, arrhythmia, seizure, infection, sinusitis, nausea
side effects of oseltamivir: aggravation of diabetes, pyrexia, seizure, unstable angina, nausea and vomiting
