Tomeglovir (BAY 38-4766) is a human cytomegalovirus (CMV) terminase complex inhibitor. Treatment with BAY 38-4766 reduced both viremia and DNAemia, as determined by a real-time PCR assay, following guinea pig cytomegalovirus (GPCMV) infection of cyclophosphamide-immunosuppressed strain 2 guinea pigs. BAY 38-4766 also reduced mortality following lethal GPCMV challenge in immunosuppressed Hartley guinea pigs. a combination of BAY 38-4766 with anti-cytomegalovirus drug ganciclovir showed antagonism. Interaction of viral DNA processing inhibitor 2-bromo-5,6-dichloro-1beta-D-ribofuranosyl benzimidazole (BDCRB) with BAY 38-4766 showed a mixed pattern of synergy and antagonism. Tomeglovir had been in phase II clinical trials by Bayer for the treatment of CMV infection. However, this development was discontinued.

Bevirimat (3-O-(3',3'-dimethylsuccinyl) betulinic acid or MPC-4326 or PA-457) potently inhibits replication of both WT and drug-resistant HIV-1 isolates and demonstrate that the compound acts by disrupting a late step in Gag processing involving conversion of the capsid precursor (p25) to mature capsid protein (p24). Bevirimat inhibits replication of both wild-type and drug-resistant HIV-1 isolates in vitro, achieving similar 50% inhibitory concentration values with both categories. Serial drug passage studies have identified six single amino acid substitutions that independently confer bevirimat resistance. These resistance mutations occur at or near the CA-SP1 cleavage site, which is not a known target for resistance to other antiretroviral drugs. Bevirimat has been in phase 2 trial for the treatment of HIV infections. Bevirimat has demonstrated a consistent pharmacokinetic profile in healthy volunteers and HIV-infected patients. The demonstration of an antiviral effect following a single oral dose of bevirimat validates maturation inhibition as a potential target for antiretroviral therapeutics in humans.

Alamifovir is a novel antiviral agent which was under development with Mitsubishi Pharma Corporation in Japan as a potential treatment for hepatitis B (HBV). Alamifovir and its hydrolyzed derivatives have shown preclinical efficacy activity against wild-type and lamivudine-resistant hepatitis B virus. The effective concentration of alamifovir required to reduce replication by 50% (EC50) for the wild-type was 0.027 uM, which is approximately 20 times less than lamivudine, and the EC50 for the lamivudine-resistant mutants was 2.6 to 3.3 uM. The mechanism of action of alamifovir appears to be via the inhibition of the protein priming reaction and the packaging reaction, thereby decreasing HBV replication. Alamifovir`s development has been discontinued.

LASINAVIR, a hydroxyethylene derivative, is highly specific human immunodeficiency virus (HIV) protease inhibitor with an IC50 of 1 nM. Its clinical development was discontinued.

Filibuvir (PF-868554), being developed by Pfizer, is an orally administered, non-nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase for the potential treatment of chronic hepatitis C (HCV) infection. Filibuvir is a potent and specific inhibitor of the virally encoded NS5B polymerase, and inhibited genotype 1 sub genomic HCV replication in the cell-based replicon system. In phase I and a IIa clinical trial in treatment-naïve patients infected with genotype 1 HCV, filibuvir monotherapy or in combination with pegylated IFNα2a/ribavirin (the standard of care [SoC] for HCV infection) for up to 4 weeks significantly reduced HCV RNA levels compared with placebo or SoC alone. However, company stopped development of the drug and the decision to halt development of the non-nucleoside polymerase inhibitor, which was in mid-stage testing, was not related to any safety issues.

Dexelvucitabine is a cytidine analogue, which has been shown to be active in both naive and HIV-experienced individuals and has in vitro activity against a variety of NRTI-resistant strains. Dexelvucitabine belongs to a class of HIV drugs called nucleoside reverse transcriptaseinhibitors (NRTIs). In the Phase IIb study most side effects were generally mild and included headache, fatigue, and gastrointestinal disorders. However, some participants developed severe hyperlipasemia and pancreatitis. Drug development is discontinued due to 40% incidence of grade 4 hyperlipasemia including one case of pancreatitis.

N-(4-Chloro-3-((3-Methyl-2-Butenyl)Oxy)Phenyl)-2-Methyl-3-Furancarbothioamide (also known as UC-781) is a thiocarboxanilide non-nucleoside reverse transcriptase inhibitor patented by Uniroyal Chemical Company, Inc. for prevention of HIV transmission. UC-781 is a potent inhibitor of reverse transcriptase-dependent pyrophosphorolysis, and purportedly restores the chain-terminating activity of zidovudine (AZT) against AZT-resistant virus. In clinical trials single and 7-day topical rectal exposure of UC-781 was safe with no significant adverse events, no detected UC-781 plasma drug levels, no significant mucosal changes, and high participant acceptability. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy.

Aplaviroc (GW873140) is a small-molecule noncompetitive allosteric CCR5 antagonist or HIV entry inhibitor (EI) that binds specifically to human CCR5 and exhibits potent anti-HIV activity in vitro in the nanomolar or subnanomolar range. Aplaviroc has exhibited potent in vivo antiviral activity (1.66 log decrease in viral load at nadir) following 10 days of monotherapy. In vitro studies of antiviral activity demonstrate that aplaviroc is active against HIV isolates from a variety of clades as well as those resistant to current HIV therapies targeting RT, PR, and gp41. However, GlaxoSmithKline has decided to terminate Phase III trials of aplaviroc after encountering additional cases of liver damage in patients taking the drug.

Amitivir [LY217896], an amino thiadiazole derivative, is an inhibitor of the enzyme inosine monophosphate dehydrogenase. Amitivir has activity against several influenza A and B viruses. Amitivir possesses broad antiviral activity in vitro and in animal models against or thomyxo-and paramyxoviruses. In phase I studies with healthy volunteers, single doses of up to 500 mg were well tolerated and had predictable pharmacokinetics. Oral LY217896 was in trial for prevention of experimental influenza A virus infection and illness in humans. LY217896 was associated with asymptomatic rises in serum uric acid levels and was ineffective in modifying the virologic or clinical course of experimental influenza A (H1N1) virus infection. Amitivir development was discontinued.

Nesbuvir (previously known as VB-19796 and HCV-796) is an inhibitor of hepatitis C NS5B RNA-dependent RNA polymerase. The drug was tested in phase II in patients with hepatitis C in combination with rebetol and peg-intron, however, its development was terminated due to safety issues.