Introduction
There are two types of viruses that commonly cause infection in man.

DNA viruses, as the name implies, contain the DNA code necessary for their replication but do not possess the necessary catalyst for self replication.  They must use a host cell mRNA polymerase to translate, transcribe, and replicate viral DNA (vDNA) into vRNA and viral proteins (vPrt) -- an exception to this rule are poxviruses, which do not require host cell polymerases to replicate.  Examples of DNA viruses include the poxvirus (smallpox, cowpox), herpesvirus (chicken pox, shingles, genital and oral herpes), adenovirus (conjunctivitis, sore throat), hepadnavirus (hepatitis B), and papillomavirus (warts).

RNA viruses contain only RNA, which must first be used as a template to form vDNA in the host cell in order to replicate.  Once this vDNA is synthesised, it may be translated, transcribed, and replicated to synthesise vRNA and vPrt.  In general, RNA viruses do not require host cell mRNA polymerase to replicate (an exception is the orthomyxovirus, which does require host cell activity).  Examples of RNA viruses include rubella (German measles), rhabdovirus (rabies), picornavirus (polio, meningitis, colds), arenavirus (meningitis, Lassa fever), arbovirus (yellow fever, tick encephalitis), orthomyxovirus (influenza), paramyxovirus (measles, mumps), and retrovirus (HIV, HTLV or human T-lymphocyte leukæmia virus causing viral-mediated leukæmia).

Other than the differences noted above, both DNA and RNA viruses enter host cells, loose their protein coats (capsids) and transfer their genetic material to the host cell nucleus.  There it is used to synthesise vRNA and/or vDNA and vPrt which is then used to produce daugher cells, as briefly illustrated above.  These daughter virions then bud and are released from the host cell, when they may infect another cell and produce additional daughter cells.

Retroviruses are also slightly different than most RNA viruses in that they possess reverse transcriptase activity and are therefore capable of synthesising their own vDNA, which is then used by the host cell (the CD4 T helper cell) to produce daughter virions, as illustrated below.

Agents Effective Against DNA Viruses --
Most agents used against DNA viruses are targeted to treat herpesviral infection.

Acyclovir and Valacyclovir (a prodrug that is bioactivated to acyclovir)
Mechanism of Action -- These drugs are guanine analogues.  Once they are taken up into the cell, they are phosphorylated by thymidine kinase.  Once this has been accomplished, they resemble and may substitute for deoxyguanisine triphosphate.  Substitution of the drug for the endogenous deoxyribonucleotide will inhibit DNA polymerase activity, which will decrease vDNA replication and vRNA and vPrt synthesis.  Additionally, they may become incorporated into the vDNA chain, in place of dGTP.  Since these drugs do not have a 3' hydroxy group, further polymerisation may not occur and vDNA synthesis is prematurely terminated.

Side Effects -- Adverse Reactions are relatively rare but may include nausea, diarrhœa, rash, headache, and very rarely nephrotoxicity and neurotoxicity (sensory disturbances, tremors, extrapyramidal side effects, delirium, seizures, and myoclonus).

Therapeutic Uses -- Herpes simplex virus (HSV) and Varicella zoster virus (Shingles, VZV)

Penciclovir and Famcyclovir (a prodrug that is bioactivated to penciclovir)
Mechanism of Action -- These agents act in a manner that is identical to that for acyclovir with the following exceptions: DNA elongation may occur with these agents, however premature termination may occur as a result of the other actions described above and these drugs are less potent that the previous two drugs.  However, they persist in the cell for a longer period of time at much higher concentrations, so that their efficacy is at least equal if not greater that the former drugs.

Side Effects -- Similar -- Testicular toxicity has been reported in animal studies.

Therapeutic Uses -- Short-term therapy of VZV.  They are also being investigated for use in hepatitis B.
 

Ganciclovir
Mechanism of Action -- The same as the previous drugs

Side Effects -- Myelosuppression especially producing neutropænia and CNS toxicity (headache, behavioural changes, convulsions, and coma)

Therapeutic Use -- Gancyclovir is used primarily for the treatment of cytomegalovirus (CMV), a viral infection of the eye that most often occurs in immunocompromised patients.
 

Cidofovir
Mechanism of Action -- The mechanism of action of cidofovir is essentially the same as that described above with the exception of the drug being a cytosine analogue rather than a guanine analogue.

Side Effects -- The primary adverse effect of concern with cidofovir is nephrotoxicity

Therapeutic Use -- Cidofovir is used primarily in the treatment of CMV.
 

Idoxuridine and Trifluridine
Mechanism of Action -- The MOA of these drugs is the same as those described above except they are analogues for thymidine and therefore may substitute for dTTP

Side Effects -- Pain, itching, inflammation (including œdema)

Therapeutic Uses -- These agents are primarily used in the treatment of HSV keratitis

Sorivudine
Mechanism of Action -- Sorivudine is also a thymidine analogue that works by a similar mechanim.

Therapeutic Use -- Sorivudine is an investigational drug that is being evaluated for use in HSV and VZV.
 

Vidarabine -- The first anti-viral of this class to be used clinically, it is rarely used now due to the high incidence of adverse reactions.
Mechanism of Action -- Vidarabine is an adenosine analogue working by a similar mechanism as described above.

Side Effects -- Anorexia, nausea, vomiting, diarrhœa, and neurotoxicity

Therapeutic Uses -- HSV encephalitis and VZV
 

Fomivirsen
Mechanism of Action -- This drug represents a new pharmacologic class of drugs, the "anti-sense" therapeutic agents.  These compounds are nucleotide sequences that are complimentary to specific strand portions of vRNA.  Mechanistically, these drugs, which may substitute for vRNA but lack the proper sequencing, result in improper protein synthesis.  Specifically, they are designed to be the opposite bases that occur in the actually vRNA sequence.  This results in the production of a non-functioning "negative" of the components necessary for normal vRNA function.   Fomivirsen specifically is a complementary anti-sense sequence of mRNA for the CMV.

Therapeutic Uses -- Fomivirsen is administered intravitriolly for the treatment of CMV.

Foscarnet (trisodium phosphonoformate)
Mechanism of Action -- Foscarnet is an analogue of pyrophosphate.  It directly inhibits HSV DNA polymerase and HIV reverse transcriptase by reversibly blocking the pyrophosphate binding site (pyrophosphate is a necessary co-factor in the functioning of these enzymes).

Side Effects -- Foscarnet may produce nephrotoxicity and hypocalcæmia (characterised by paræsthesias, arrhythmias, and seizures).  The hypocalcæmia is likely due to phosphate imbalance, since the drug possesses numerous phosphate groups that may be liberated upon metabolism.

Therapeutic Uses -- Foscarnet is used primarily in the treatment of CMV retinitis and acyclovir-resistant HSV.

Zidovudine (azidothymidine, AZT)
Mechanism of Action -- AZT is a thymidine analogue that inhibits the enzyme reverse transcriptase (a DNA polymerase) to inhibit the formation of vDNA and also competitively inhibits thymidylate kinase to reduce TTP.

Side Effects -- Initial side effects include headache, nausea, vomiting, insomnia, and myalgia.  The primary concern, however, is granulocytopænia and anæmia.

Therapeutic Use -- AZT is the drug of choice for HIV infected patients with low CD4 cell counts.

Stavudine
Mechanism of Action -- The same as AZT

Side Effects -- The primary side effect is painful, sensory peripheral neuropathy

Therapeutic Use -- Stavudine is used primarily in the treatment of HIV that has become resistant to conventional therapy.

Didanosine (dideoxyinosine, DDI)
Mechanism of Action -- The MOA of DDI is the same as that described for AZT except that it is an adenosine analogue.

Side Effects -- Diarhœa, rash; the major concerns are less frequent peripheral neuropathies and pancreatitis.

Therapeutic Use -- Advanced cases of HIV
 

Zalcitabine
Mechanim of Action -- Zalcitabine is a cytosine analogue that works by a similar mechanism.

Side Effects -- Rash, fever, and nausea early in therapy.  The major concern is neuropathy that is manifest as pain, paræsthesia, and hypæsthesia.

Therapeutic Use -- Zalcitabine is used in combination with AZT for the treatment of advanced HIV, or early with AZT resistant HIV.
 

Lamivudine
Mechanism of Action -- The same as that for zalcitabine

Side Effects -- The major advantage of lamivudine is that it produces no peripheral neuropathies.  However, resistance develops rapidly to its effectiveness.  Curiously, if lamivudine is combined with AZT, the resistance is less pronounced and the combination may exert quite good activity, even when some resistance has developed to either agent singly.

Therapeutic Uses -- Primarily used for HIV, but may also be effective in treating hepatitis B.
 

Abacavir
Mechanism of Action -- Abacavir is a guanosine analogue that works by a similar mechanism.

Side Effects -- Hypersensitivity in 5% of the population, rash, fever, nausea, vomiting, diarrhoea, and disseminated intravascular coagulation are also possible.  Additionally, clinical reports have linked abacavir therapy with lactic acidosis and hepatomegaly associated with steatosis.

Therapeutic Uses -- HIV
 

Nevirapine -- Nevirapine, Delavirdine, Loviride, and Efavirenz are non-nucleotide inhibitors of reverse transcriptase.  They do NOT substitude for a ribonucleotide but rather directly inhibit the enzyme.  The potential advantage of non-nucleotide inhibitors is less development of resistance. Efavirenz has the added advantage of once daily dosing.

Idinavir, Ritonavir, Saquinavir, and Nelfinavir

Mechanism of Action -- These drugs inhibit the enzyme protease, which is necessary for the final maturation of daughter virions.  Inhibition of protease will inhibit the final integration and assembly of viral enzymes and viral structural proteins.

Side effects --

Indinavir may produce hyperbilirubinæmia, nephrolithiasis, thrombocytopænia, and GI upset.
Ritonavir -- GI upset and circumoral paræsthesias
Saquinavir and Nelfinavir -- GI upset
Drug Interactions -- All four drugs may inhibit cytochrome CYP450, leading to numerous interactions with drugs metabolised by that system.

Therapeutic Uses -- These agents are used as adjuncts to reverse transcriptase inhibition in HIV infections.

Amantidine and Rimantidine (more active)
Mechanism of Action -- These agents inhibit the M2 protein of the virus to decrease hydrogen ion influx (through a specific H⁺ ion channel).  Consequences of this action results in a two-fold mechanism of action
1) Inhibit viral uncoating as it enters the host cell (through inhibition of H⁺ influx)
2) Inhibit the coating process (inhibits hemagluttinin) as the daughter virion prepares to leave the host cell (through increased acidity extravirally).
Side Effects -- GI upset and CNS toxicity (nervousness, lightheadedness, decreased concentration, insomnia)

Therapeutic Uses -- Influenza A viral infections, resistance may develop to their effects.
 

Ribavirin
Mechanism of Action -- Ribavirin is a guanine analogue that acts in a manner similar to the other nucleoside analogues discussed previously.

Side Effects -- Local side effects (nasal irritation, sneezing, burning -- it is a locally administered formulation).  Systemic side effects include hæmolysis, bone marrow suppression, and GI upset.

Therapeutic Uses -- Respiratory syncytial virus (RSV) and Lassa fever.  It is being evaluated for use in the treatment of Hanta virus infections.
 

Interferons -- there are three major classifications of interferon -- alpha interferons, beta interferons, and gamma interferons.  Human recombinant interferon alpha (interferon alfa) is the major one used clinically.
Mechanism of Action -- These endogenous cytokines activate host immune responses at several steps.  Specific actions of interferons include
Decreased penetration and uncoating of viruses

Decreased synthesis of mRNA (through increase methylase activity)

Decreased synthesis of proteins (through increased phosphokinase activity, increased phosphodiesterase activity to cleave tRNA, and increased oligoadenylase synthase activity to increase RNAse activity and cleave RNA)

Decrease virion assembly -- through increased glycosyltransferase activity

Decrease budding and release of daughter virions -- through changes in the host cell membrane
 

Side Effects -- Flu-like syndrome (tolerance usually develops to this effect) consisting of fever (usually subsides within 12 hr), chills, headache, myalgia, arthralgia; also, GI upset, bone marrow suppression, neurotoxicity, thyroid dysfunction, and cardiotoxicity (especially with interferon alpha).  (NOTE the wide range of adverse effects likely is a reflection of the importance of cytokine activity, bodywide.)

Therapeutic Uses -- Primarily used for hepatitis B and papillomavirus infection.  It is also used for HSV, VZV, CMV, HIV, and HTLV.