2009 Mark Tuttle

Herpesvirus Antivirals
Name Target Mechanism Pharmacokinatics Side effects
Acyclovir
Acyclo-guanosine
(Guanosine anologue)
-HSV1=HSV2 V!V
"MV#HHV-$
-%e&uces sy'(to's an&
&uration
-)oes *+T (re,ent recurrence
-+nly (artially su((resses ,iral
s-e&&ing
-Goo& at getting into "*S so
re&uces -er(es ence(-alitis
'ortality .y /00
-)*A synt-esis c-ain
ter'inator
-1irst (-os(-orylate& .y
T-y'i&ine kinase
- T-is ste( only occurs
in ,irus-in2ecte& cells
-ig- s(eci2icity
-3-os(-orylate& t4ice an&
t-rice .y ot-er cell
en5y'es
- -%enal 6 "*S at -ig- (arenteral
&oses
-%eally goo& at getting into "*S
tra&eo22 4it- usage as -er(es
ence(-alitis treat'ent
Valcyclovir
7-,alyl ester o2
acyclo,ir
(Guanosine anologue)
-Meta.oli5e& to acyclo,ir8
.etter a.sor(tion across cell
'e'.ranes
-
Gangyclovir
Acyclo-guanosine
(Guanosine anologue)
-Treat'ent o2 "MV retinitis
-3re,ention o2 acti,e &isease in
i''unoco'(ro'ise&
-)*A synt-esis c-ain
ter'inator
-7ong -al2 li2e (1$ -rs in
cells) goo& .ecause
,iruses can re(licate slo4ly
-"*S
-Teratogenicity
-Myelosu((ression
Penciclovir
(Guanosine anologue)
-9 -er(es 5oster (V!V) HHV-: -)*A synt-esis c-ain
ter'inator
-Accu'ulates in cells to
-ig-er le,els t-an acyclo,ir
an& -as a longer -al2 li2e
(12 -ours)
-
Foscarnet
(3yro(-os(-ate
analogue)
-"MV retinitis
-Acyclo,ir-resistent -er(es
nly used in life!threatening
cases
-;lock )*A synt-esis .y
.locking -er(es
(oly'erase < an& =
(-os(-ate .in&ing sites
- -%enal to>icity
-Hy(ocalce'ia
-"*S-to>icity
Videra"ine -HSV keratocon?uncti,itis
To(ical a&'inistration
- -
Famciclovir -Genital -er(es an& V!V (HHV
2@:)
-More ra(i& resolution o2 V!V
(ain t-an acyclo,ir
- - -
Formivirsen
#Vitravene$
-"MV retinitis
Antra,itreal in?ection
-3-os(-orot-ioate
antisense oligonucleoti&e
against "MV A''e&iate
Barly '%*A
-1or's &s%*A an&
acti,ates -ost silencing
en5y'es
- -
Trifluridine solution
%do&uridine solution
Vidar"ine ointment
-Her(es keratitis - - -
2009 Mark Tuttle
Antiretrovirals
NucleoS%'( )everse Transcriptase %nhi"itors #N)T%s$
!vudine
Name Target Mechanism Side effects
*idovudine #A*T$
T-y'i&ine a5i&o
analogue
-%etro,iruses (HAV) -3-os(-orylate& .y cell en5y'es to tri-
(-os(-ate &eri,ati,e
-Tri(-os(-ate A!T accu'ulates in unin2ecte&
cells also8 soC
- Granulocyto(enia
- Ane'ia
-;locks ,iral nucleic aci& synt-esis
-"-ain ter'inator (like acyclo,ir)
*ucleoti&es .in& at D(al'E o2 rig-t-
-an&e& %e,erse Transcri(tase
+amivudine #,T-$
"yti&ine-&eri,ati,e
-%etro,iruses (HAV)
-"-ronic He(atitis ; (Hepadna
,irus)
-
'idanosine #''%$
)i&eo>y inosine
&eri,ati,e
(Guanosine (recursor)
-Treat'ent o2 A!T-resistant HAV -3ancreatitis in /0 o2 (atients
Stavudine #'.T$
T-y'i&ine analogue
-%etro,iruses (HAV) -
Non!NucleoS%'( )everse Transcriptase %nhi"itors #NN)T%s$
Nevirapine -%etro,iruses (HAV) -;locks ,iral nucleic aci& synt-esis
-Target t-e structure o2 %e,erse
Transcri(tase .y .in&ing at a &i22erent site
t-an nucleosi&es
(not t-e D(al'E (art o2 %T)
-He(atoto>icity
-3otentially 2antal ras-
NucleoT%'( )everse Transcriptase %nhi"itors
Tenofovir -%etro,iruses (HAV) -;locks ,iral nucleic aci& synt-esis
-/sed in palce of N)T% in com"ination
therapy
-
H%V Protease inhi"itors
!navir
%ndinavir -Fi&ney stones in 2-/0 o2 (atients
All (rotease
in-i.itorsC
-7i(o&ystro(-y
-Gorsens &ia.etes
-0lock cleavage of viral polyproteins
-An-i.it ,iral D'aturationE an& ,irion 2or'ation
-A&'inistere& in co'.ination 4it- ot-er HAV &rugs to (re,ent
&e,elo('ent o2 resistance
Sa1uinavir -)iarr-ea8 lo4er GA &istur.ances
)itonavir -An&uces an& in-i.its "ytoc-rone
3H/0
-Ancrease& .loo& triglyceri&es
-)iarr-ea
+opinavir2 Nefinavir2
Amprenavir
H%V Fusion %nhi"itors
Name Target Mechanism Side effects
(nfuvirtide
:$ AA (e(ti&e
a&'inistere&
-HAV-1 +*7I -;in&s G3H1 glyco(rotein o2 HAV-18 (re,ents
2usion
-)oes *+T .in& HAV-2 G3H1
-
2009 Mark Tuttle
su.cutaneously
HAA)T3 Highly active antiretroviral therapy Monitor ,iral loa& .y %T-3"%
- *idovudine #A*T$
- +amivudine #,T-$
- an NN)T%
- a protease inhi"itor
%nfluen4a Antivirals
Name Target Mechanism Side effects
Type A (-u'ans8 .ir&s8 ani'als) Type 0 (-u'ans) Type - (-u'ans)
- Ty(ing is .ase& on internal Matri> (rotein (M1) an& *ucleoca(si& (* or *3) T-ese nee& to .e 'atc-e& to eac- ot-er
- "annot resort .et4een ty(es .ecause 2or e>a'(le Ty(e A 'atri> (rotein 4ill only 4ork 4it- Ty(e A nucleoca(si&
- Ty(e As are su.ty(e& .y antigenic structure o2 en,elo(e glyco(roteins (e>ternal (roteins)
o B>J A in2luen5a#Sy&ney#/-9K-like (H:*2)
H or HA is -e'aglutinin (.in&s to ,iral rece(tor sialic aci& on -ost 2or entry)
* or *A is neura'ini&ase (.in&s an& clea,es sialic aci& 2or ,iral release)
Amantidine (Sy''etrel) -Type A influen4a only
.ecause ty(e ; 4ill release
at a -ig-er (H an& &onLt
nee& M2 2unction as 'uc-
-0lock M5 ion channel 2unction8 (re,enting in2lu> o2 H6 an&
&ecrease in (H8 t-us "locking viral fusion6replication
-;locks t-e release o2 nucleoca(si&s 2ro' t-e 'atri> (rotein
s-ell
-3re,ents nucleoca(si& 'igration to t-e nucleus an& t-us
(re,ents re(lication
-*euroto>icity
4ill .lock A"- %ece(tor
-"ar&iac arr-yt-'ias
-Teratogenic in ani'als
)imantidine (1lu'a&ine) -Sa'e 'ec-anis' .ut 'ore (otent an& e>tensi,ely
'eta.oli5e&
-Sa'e .ut less "*S to>icity
-*ee& to a&?ust &ose in ki&ney
insu22iciency (atients
steltamivir (Ta'il2lu)
Sterically in-i.it non-
acti,e site 4it-
-y&ro(-o.ic (ocket
-Type A and 0 influen4a
-%e&uces sy'(to's
-3re,enti,e i2 use&
(ro(-ylactically
-0lock Neuraminidase #NA$ an& t-us "lock viral release
-"o'(etiti,e in-i.itors neura'ini&ase (*A) rece(tor since
t-ey are sialic aci& analogues
o Sialic aci& nor'ally -as an +H in t-e acti,e site o2 *A
-
*anamivir (%elen5a)
;in&s an& .locks acti,e
site
%nterferon Antivirals
Name Target Side effects
)ecom"inant %FN!
75"
-He(atitis ;
-Fa(osiLs Sarco'a (HHV-M)
-He(atitis "
-Ma?or to>icityC ;one 'arro4 su((ression
-)e(ression
P(G!%FN!7 -Si'ilar targets .ut 'ore sta.le in circulation 4it- 20> increase in -al2
li2e
-Gorks .est 4-en co'.ine& 4it- ri.a,irin8 as 4it- un'o&i2ie& A1*
-
)SV )espiratory Antivirals
Name Target Mechanism Side effects
Palivi4uma" -%SV -Hu'ani5e& 'ouse 'onoclonal anti.o&y (MA;) -
2009 Mark Tuttle
1or in2ants N2 4it- lung
(ro.le'
s(eci2ic 2or )SV F!glycoprotein 0locks fusion of
virus
)i"avirin
Guanosine analogue
-%SV
-He(atitis " 4it-#3BG-A1*-9
- MutagenicC instea& o2 c-ain ter'inating8 uses
-ost re(air 'ac-inery to s4itc- GO t-ro4s ,iral
geno'e into error-catastro(-e ((4nt)
-%e,ersi.le &ecrease in (ul'onary
2unction (aerosol)
-He'olytic ane'ia
-Teratogenic
-)e(ression#suici&al ten&encies (oral)
%i.a,irin %esistanceC *e4 strain -as &e,elo(e& t-at -as a (oly'erase t-at 'o,es 2aster an& 4ill only use -ig--
Puality nucleoti&es (4ill not use %i.a,irin)J Ho4e,er8 t-is ne4 strain 4ill *+T go to t-e "*SJ Goo&Q B>J 3olio