Pleconaril (Picovir) is an antiviral drug that was being developed by Schering-Plough for prevention of asthma exacerbations and common cold symptoms in patients exposed to picornavirus respiratory infections. Pleconaril binds to a hydrophobic pocket in viral protein 1, the major protein which comprises the capsid (the outer "shell") of picornaviruses. In enteroviruses, this prevents the virus from exposing its RNA, and in rhinoviruses, it also prevents the virus from attaching itself to the host cell. The results of two randomized, double-blind, placebo studies found Pleconaril treatment could benefit patients suffering from colds due to picornaviruses. Participants in the studies were healthy adults from Canada and the United States, with self-diagnosed colds that had occurred within 24 hours of trial enrollment. Participants were randomly given a placebo or two 200 mg tablets to take three times daily for five days. To increase absorption it was recommended to be taken after a meal. To monitor the effectiveness of Pleconaril, Participants recorded the severity of their symptoms and nasal mucosal samples were obtained at enrollment, day 3, day 6 and day 18. The two studies had a total of 2096 participates and more than 90% (1945) completed the trial. The most common reason for a participant not finishing the trial was an adverse event. Pleconaril treatment showed a reduction in nose blowing, sleep disturbance, and less cold medication used. The U.S. Food and Drug Administration rejected pleconaril in 2002 due to the side effects. The most commonly reported side effects were mild to a moderate headache, diarrhea, and nausea.

Tromantadine HCl under brand name Virumerz is used to treat the herpes simplex virus by inhibiting the cellular process such as glycoprotein processing, which occurs after the synthesis of the fusion protein but before its expression on the cell surface.

Inosine pranobex is an antiviral drug that is a combination of inosine and dimepranol acedoben (a salt of acetamidobenzoic acid and dimethylaminoisopropanol) in a ratio of 1 to 3. Inosine pranobex is used to treat mucocutaneous infections due to herpes simplex virus (type 1 and/or type II), genital warts as adjunctive therapy to podophyllin or carbon dioxide laser, and subacute sclerosing panencephalitis. The in vivo antiviral and activity of inosine pranobex is believed to result from an enhancement of host immune responses due to the drug. The drug does not by itself stimulate resting lymphocytes, but augments immunological processes by lymphocytes once they have been triggered by mitogens or viral antigens.

Methisazone is N-methyl-isatin beta-thiosemicarbazone. This is one of a series of isatin beta-thiosemicarbazones which have been shown in the laboratory to have antiviral activity against vaccinia and variola viruses. It has been reported to be effective for smallpox prophylaxis.

Enfuvirtide is a linear 36-amino acid synthetic peptide that inhibits the fusion of HIV-1 with CD4 cells. Enfuvirtide works by disrupting the HIV-1 molecular machinery at the final stage of fusion with the target cell, preventing uninfected cells from becoming infected. Enfuvirtide interferes with the entry of HIV-1 into cells by inhibiting fusion of viral and cellular membranes. Enfuvirtide binds to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein and prevents the conformational changes required for the fusion of viral and cellular membranes. Enfuvirtide is indicated for the treatment of HIV-1 infection, in combination therapy with other antiretrovirals, in patients where all other treatments have failed. Common adverse drug reactions associated with enfuvirtide therapy include: injection site reactions (pain, hardening of skin, erythema, nodules, cysts, itch; experienced by nearly all patients, particularly in the first week), peripheral neuropathy, insomnia, depression, cough, dyspnoea, anorexia, arthralgia, infections (including bacterial pneumonia) and/or eosinophilia.

BARACLUDE® is the tradename for entecavir, a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). It inhibits all three steps in the viral replication process. By competing with the natural substrate deoxyguanosine triphosphate, entecavir functionally inhibits all three activities of the HBV polymerase (reverse transcriptase, rt): (1) base priming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. Upon activation by kinases, the drug can be incorporated into the DNA which has the ultimate effect of inhibiting the HBV polymerase activity. Entecavir is used for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

The potential antiviral effect of adefovir, an acyclic nucleoside phosphonate analog of 2′-deoxyadenosine monophosphate, was first studied by Holý and De Clercq in 1980s. Adefovir is an acyclic nucleotide analog of adenosine monophosphate which is phosphorylated to the active metabolite adefovir diphosphate by cellular kinases. Adefovir diphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate deoxyadenosine triphosphate and by causing DNA chain termination after its incorporation into viral DNA. Oral adefovir dipivoxil is effective and generally well tolerated in HBeAg-positive and -negative patients chronically infected with wild-type or lamivudine-resistant HBV.

(R)-9-(2-Phosphonylmethoxypropyl)adenine (PMPA known as tenofovir) is an antiviral drug. Diphosphate of PMPA acts as a selective inhibitor of the HIV-1 reverse transcriptase. Tenofovir disoproxil was approved for clinical use for the treatment of HIV infection (AIDS) and chronic HBV infection.

Amprenavir is an inhibitor of HIV-1 protease. Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral gag and gag-pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles. Amprenavir-containing combination regimens have shown virological efficacy, and have generally been well tolerated, in patients with HIV infection (primarily treatment-naive or protease inhibitor-naive). Fosamprenavir (GW433908, Lexiva, Telzir) is an oral prodrug of amprenavir, with a reduced daily pill burden. The use of protease inhibitors has also been associated with dyslipidemia and an increased risk of cardiovascular disease. Amprenavir activates Pregnane X receptor to mediate dyslipidemia.

Oseltamivir phosphate is an ethyl ester prodrug requiring ester hydrolysis for conversion to the active form, oseltamivir carboxylate. Oseltamivir carboxylate is an inhibitor of influenza virus neuraminidase affecting release of viral particles. Oseltamivir is a well tolerated orally active neuraminidase inhibitor which significantly reduces the duration of symptomatic illness and hastens the return to normal levels of activity when initiated promptly in patients with naturally acquired influenza.