antivirals Flashcards
what do viruses consist of?
proteins, nucleic acid (DNA or RNA) and potentially a lipid envelope
what viruses typically have or do not have an envelope?
those in the GIT do not and those in respiratory do
what proteins are there in a virus?
structural - part of virus or non-structural - enzymes for replication and taking over the host cell machinery
what is an example of a very large virus?
HSV
what do double DNA stranded viruses do?
they are very large and code for many proteins
what are viruses?
they are obligate parasites - replicate in host and take over their machinery
what is found in the core of a RNA virus?
RNA and reverse transcriptase
what types of viral infections are there?
acute (RNA) or chronic (DNA) - those larger viruses are likely to stay in the host for longer - usually remain for a lifetime
what are examples of acute viruses?
they are generally RNA and these are mumps, influenza, measles and Hep A
what are examples of chronic viruses?
generally DNA
latent - with or without recurrence - herpes simplex or cytomegalovirus or persistent - Hep B and C, HIV and HTLV
what are the characteristics of virus syndrome?
non vesicular rashes - measles, rubella, parvovirus, adenovirus and HHV6
vesicular rashes - fluid filled lesions - chickenpox (HHV3), herpes simplex (HHV1/2) and enterovirus
what are examples of respiratory viruses?
coronavirus (and SARS), influenza, parainfleunza virus, human metapneumovirus, infleunza, RSV giving broncholitis and rhinovirus
what are examples of GIT viruses?
mainly RNA - rotavirus, noravirus, sapovirus, astrovirus and adenovirus group F
what can result in neurological disease and what viruses can cause this?
encephalitis or meningitis - HSV, enteroviruses, Japanese encephalitis virus, Nipah virus and rabies
what are blood borne viruses?
they can be hepatitis viruses - HBV or HCV or retroviruses - HIV1,2 or HTLV 1/2 - can be associated with neurological but most people will not be affected
when would you use antivirals?
where there are acute infections in the general population with high risk of complications, chronic infections such as HIV, HBV or HCV, infections in immunocompromised (post transplant, immunosupressive therapies and primary immunodeficiences), treat invasive disease (encephalitis or disseminated HSV), primary oral-labial or genital herpes, prophylaxis for frequent reactivations
what does self limiting mean?
most viruses get better on own within few days to weeks - longer if immunocompromised
who does disseminated HSV affect?
neonates and immunocompromised
what is used for treatment of HSV?
aciclovir
what is aciclovir used for in HSV?
prophylaxis - lower dose to prevent recurrence
primary oral labial or genital herpes
treat invasive disease - encephalitis, disseminated HSV and severe first time infection
what is the treatment for VZV?
aciclovir
why is acyclovir used for VZV?
broad spectrum disease
infection is more severe in adults
need to be started as soon as possible - within 2 days
treat shingles - reactivation when dormant in ganglia
if over 60 (reduce incidence of post herpetic neuralgia), involves eye or immunocompromised
what is used to treat influenza?
neuraminidase inhibitors oseltamivir - oral and zanamavir - inhaled
when would you use prophylactic treatment for influenza?
to treat high risk patients in hospital or community - chronic neurological, hepatic, renal, pulmonary and chronic cardiac disease, diabetes, sever immunocompression, age over 65, during and up to 2 weeks post partum pregnancy, morbid obesity, children under 6 months - 90% effective in preventing infection
what is the treatment of chronic viruses?
lifelong treatment up to 95% of the time except HCV which is a RNA virus and can be cured
what are the problems with antiviral treatment?
need to avoid emergence of resistance, challenge to take and maintain adherence and antiviral toxicity
what is the viral life cycle?
it is viral attachment to the cell through a receptor and then cell entry and virus uncoating. Early proteins are then produced which are viral enzymes and then replication occurs. There is then late transcription and translation for viral structural proteins, virus assembly, release and mutation
what are targets for molecular inhibition?
all viruses encode unique proteins that are essential for replication and infectivity and allows the virus to take over intracellular machinery.These are molecular inhibition targets
what are polymerases in viruses used for?
most viruses have their own or use the host’s. These are to convert
a) DNA to DNA in eukaryotes and DNA viruses and also DNA to RNA in these
b) RNA to RNA in RNA viruses
c) RNA to DNA in Hep B and retroviruses
what comprises a nucleotide?
triphosphate, base and ribose sugar
what inhibits reverse transcriptase?
nucleotide reverse transcriptase inhibitors such as AZT
what is AZT?
it is a NRTI that is based on a thymidine model - azidothymidine - it is used in HIV treatment but not commonly as it causes anaemia
what are HIV NTRIs structures?
they are either pyrimidine or purine analogues - for thymidine is zidovudine and cytosine is lamivudine and for adenosine is abacavir and for guanosine is tenofovir
why are NRTIs also active against HBV?
it contains reverse transcriptase and converts RNA to DNA to make new genomes - it is a DNA virus
what is the treatment for HIV and HBV?
used two drugs in combination - lamiduvine and tenoflovir
why is aciclovir/acyclovir (same thing) safe?
there is no extension with it - it is a chain terminator
what is aciclovir used for?
HSV and VZV
what is aciclovir?
it is an analogue of guanosine
what has a similar structure but slightly different function to aciclovir?
ganciclovir - it is not a chain terminator
what is ganciclovir used or?
CMV and HHV6 and sometimes for HSV and VZV
what types of drugs are the antivirals for HSV?
they are polymerase inhibitors
what is a HCV RNA PNI?
it is a HCV RNA polymerase nucleotide inhibitor
what is an example of a HCV RNA PNI and what is it used for?
sufobuvir - analogue of deoxycytidine - effective for Hep with very good availability
what are NNRTIs?
they are non nucleotide reverse transcriptase inhibitors
what are NNRTIs used for?
most are active against viral enzymes rather than host enzymes because they mimic nucleotides - they will bind to different parts of the enzyme to stop them from working and are useful in Hep C and HIV
what are examples of NNRTIs?
nevirapine and
efavirenz
what are proteases from host used for?
they are important for viral replication to ensure the proteins fold properly
what are examples of protease inhibitors?
HIV - ritonavir - used to boost PI levels, atazanavir and darunavir
HCV - grazoprevir and paritaprevir
what are entry inhibitors?
they are T20 fusion inhibitors given by IM or chemokine receptor antagonists to work on the CCR5 receptor that prevent HIV from entering cells
how does HIV enter cells?
through the CD4 molecule with a CCR5 co-receptor
what are integrase inhibitors used for?
HIV drugs and retroviruses
what does HAART stand for?
highly active antiretroviral therapy
what comprises HAART?
2NRTIs + NNRTIs or 2 NRTIs + boosted PIs or integrase inhibitors
what is the issue with HAART?
have to use fixed drug combinations to switch off viral replication and take it life long - suppress replication but cannot fully remove and also can cause adverse side effects and reduce immune system
what is the role of the immune system in HAART?
it will clear out the remaining viruses that HAART cannot
what is the rough size of the HIV genome?
around 9000 nucleotides and every genome will contain at least one mutation
when will a strain predominate?
when they have a selective advantage over other strains
what results in resistance to Lamiduvine?
the M184V mutation
how can the enzymes of viruses mutate?
genomes are more prone to error and therefore can change polymerase in response to antiviral therapy, T cell immunity or host immunity
why is a fixed combination of drugs needed for HIV?
due to mutations - two or more drugs makes it impossible for viruses to have that many mutations in one time - if do not take drug then can mutate and then become resistant
what is the treatment of HCV?
they now have directly acting antivirals rather than combined with interferons - generally use combination therapy with 2 or 3 agents for 8-12 weeks with cure rates of over 95%.
why might HCV require different combinations of of antivirals?
different genomes may need different antivirals although some will work against all genotypes
what is the benefit of newer therapies?
newer therapies are quite well tolerated - side effects are affecting bone and tissues
how do antivirals work generally?
the block a particular stage of viral replication
when should you give antivirals for acute infections?
as soon as possible after symptoms develop
