Antiviral efficacy

A large number of a-hydroxybenzylbenzimidazole [50-97-5] (HBB, 39), C24H22N2O, derivatives has been prepared and extensively studied as selective inhibitors of the RNA containing enterovimses (91). Although none of these derivatives have shown any antiviral activity in animals, l,2-bis(5-methoxy-2-benzimidazol-2-yl)-l,2-ethanediol [16656-27-2] (40), C2gH2gN404, was found to be active against an experimentally induced rhino vims infection in chimpanzees (92). However, the in vivo antiviral efficacy was accompanied by significant toxicity. 

Reiser M, Hinrichsen H, Benhamou Y, Reesink HW, Wedemeyer H, Avendano C, Riba N, Yong CL, Nehmiz G, Steinmann GG (2005) Antiviral efficacy of NS3-seiine protease inhibitor BlLN-2061 in patients with chronic genotype 2 and 3 hepatitis C, Hepatology 41 832-835... 

IFN-y has potent activity against HCV in the subgenomic replicon system (Dash et al. 2005 Frese et al. 2002 Lanford et al. 2003). Synergistic immunomodulatory effects of IFN-ylb and IFN-a have been reported (Wang et al. 2006). However, a pilot study of IFN-y at a dose of 100-400pg three times per week showed no antiviral efficacy in patients infected with HCV genotype 1 who had not responded to standard therapy or who had relapsed (Soza et al. 2005). 

IFN-a was first nsed empirically in chronic hepatitis B in 1986 (Peters et al. 1986). The effect of hnman recombinant IFN-a on lymphocyte proliferation and differentiation was stndied in 18 patients with chronic hepatitis B. Inhibition of immnnoglob-nlin synthesis was observed, and the anthors postnlated that the immnnomodnlatory effect of IFN-a could be important in the therapentic response of chronic hepatitis B (Peters et al. 1986). The first study to evaluate the antiviral efficacy of IFN-a involved nine patients, who received different doses administered three times a week for two weeks. Two of them entered snstained remission, with nndetectable HBV DNA, loss of HBeAg, and ALT normalization (Dooley et al. 1986). Two forms of IFN-a have been used in the treatment of chronic hepatitis B, namely standard and pegylated IFN-a. 

The antiviral efficacy of IFN-p administered for 24 weeks at a dose of 3 million units daily has been studied in a small series of HBeAg-positive patients. HBe seroconversion was observed in half the patients and ALT normalization in four patients out of five (Kagawa et al. 1993). Sequential therapy with lamivudine and IFN-p has been tested in HBeAg-positive patients (Enomoto et al. 2007). A sustained virological response was achieved in only 7 (29%) of the 24 patients, 24 weeks after the end of therapy. In a pilot study of IFN-p therapy in 29 patients in whom IFN-a therapy had failed, HBV DNA became undetectable in 6 patients (21%) (Munoz et al. 2002). 

The antiviral efficacy of IFN-A, has been evaluated in vitro in hnman hepatocyte-derived cells. IFN-X rednced HBV replication but the results suggested that antiviral efficacy in vivo wonld be limited (Hong et al. 2007). 

HavUr DV, Richman DD (1996) Viral dynamics of HIV implications for drug development and therapeutic strategies. Ann Intern Med 124(11) 984—994 Hinrichsen H, Benhamou Y, Wedemeyer H, Reiser M, Sentjens RE, Calleja JL, Foms X, Erhardt A, Cronlein J, Chaves RL, Yong CL, Nehmiz G, Steinmann GG (2004) Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype I patients. Gastroenterology 127(5) 1347-1355... 

After the initial reports of the antiviral efficacy of BILN 2061 a large number of reports disclosing macrocyclic (Figure 2.10) [71, 119-124] and acyclic (Figure 2.11) [125-135] analogues have appeared. For some of these compounds an acyl sulfonamide has been also reported at the C-terminus. 

Viral protease cleaves precursor proteins into proteins required for viral replication. The inhibitors of this protease (saquinavir, ritonavir, indinavir, and nelfinavir) represent abnormal proteins that possess high antiviral efficacy and are generally well tolerated in the short term. However, prolonged administration is associated with occasionally severe disturbances of lipid and carbohydrate metaboUsm Biotransformation of these drugs involves cytochrome P450 (CYP 3A4) and is therefore subject to interaction with various other drugs inactivated via this route. 

In its original formulation as a hard gel capsule (saguinavir-H Invirase), oral saquinavir is pooriy bioavailable (only about 4% after food). However, reformulation of saquinavir-H for once-daily dosing in combination with low-dose ritonavir has both improved antiviral efficacy and decreased gastrointestinal adverse effects. 

Singh LM, Gupta G. 1985. Antiviral efficacy of Homeopathic drugs against animal viruses. Br Horn J 74 168-174. 

Afouna, M.I., et al. 2003. Effect of azone upon the in vivo antiviral efficacy of cidofovir or acyclovir topical formulations in treatment/prevention of cutaneous HSV-1 infections and its correlation with skin target site free drug concentration in hairless mice. Int J Pharm 253 159. 

Antiviral Efficacy and Clinical Use. Cidofovir (Vis-tide) is used primarily to treat CMV retinitis in people with AIDS.111 When used clinically, this drug is often combined with probenecid, an agent that inhibits renal excretion of cidofovir, thereby providing higher plasma levels of this antiviral agent.112... 

Antiviral Efficacy and Clinical Use. Docosanol (Abreva) is applied topically to treat blisters and cold sores caused by herpes virus simplex.42 This drug is available as an over-the-counter product, and is used primarily to treat recurrent outbreaks of orofacial herpes lesions. 

Antiviral Efficacy and Clinical Use. Penciclovir (Denavir) is similar to acyclovir in terms of its antiviral effects and clinical indications. However, penciclovir is absorbed poorly from the gastrointestinal tract. This drug is primarily administered topically to treat recurrent herpes simplex infections of the lips and face (cold sores).58... 

Antiviral Efficacy and Clinical Use. Fomivirsen (Vitravene) is injected into the vitreous humour to treat CMV infection in the eye.42 This drug is often used to treat ocular CMV infections that are resistant to more traditional agents such as ganciclovir or fos-carnet. 

Antiviral Efficacy and Clinical Use. Foscarnet (Fos-cavir) is primarily given to treat CMV retinitis in patients with AIDS.6,24 This agent may also help control other infections in patients with a compromised immune system, including serious cytomegaloviral infections (pneumonia, gastrointestinal infections) and some herpesvirus infections (herpes simplex, varicella-zoster). 

Antiviral Efficacy and Clinical Use. Imiquimod (Aldara) is applied topically to treat condylomata acuminate infections that cause genital and perianal warts.42 It can also be used to treat certain skin conditions such as actinic keratoses of the face and scalp. 

Antiviral Efficacy and Clinical Use. Trifluridine (Viroptic) is administered by eye drops to treat local eye infections associated with herpes simplex virus that is, herpes virus-related keratitis and keratoconjunctivitis.42... 

Antiviral Efficacy and Clinical Use. Oseltamivir (Tamiflu) and Zanamivir (Relenza) are effective against influenza virus types A and B. These drugs can reduce the duration and severity of flu symptoms if the drug is administered within 48 hours after symptoms first appear.22,46 These drugs can also be taken pro-phylactically to reduce the risk of getting the flu, especially in people who are at high risk (older adults, people with respiratory disorders), or in cases where an individual is exposed to a family member or someone else with the flu.3... 

Antiviral Efficacy and Clinical Use. These drugs inhibit an enzyme known as HIV protease. This enzyme is needed to manufacture specific HIV proteins, in-... 

Antiviral Efficacy and Clinical Use. Ribavirin (Vira-zole) is active against several RNA and DNA viruses, including respiratory syncytial virus (RSV).106 Clinically, this drug is used to treat severe RSV pneumonia in infants and young children,106 and RSV in certain adult populations, including the elderly, people with cardiopulmonary problems, and people with a compromised immune system.29 Ribavirin may also be useful as a secondary agent in the treatment of influenza A and B in young adults. The combination of ribavirin and interferons (see section on Interferons, later) is often the treatment of choice in chronic hepatitis C infection.30 72... 

Antiviral Efficacy and Clinical Use. Vidarabine (Vira-A) was the first systemic agent used to treat herpesvirus infections, including CMV, herpes simplex virus, and varicella-zoster virus.42 In the past, this drug was administered by continuous intravenous infusion to treat severe systemic infections caused by these viruses, but systemic use of vidarabine has been replaced by safer and less toxic agents. Vidarabine is currently used primarily to treat local viral infections of the eye (e.g., herpes simplex keratoconjunctivitis) it is applied topically by ophthalmic ointment to treat these infections. 

In its original formulation as a hard gel capsule (saquinavir-H Invirase), oral saquinavir was poorly bioavailable (about 4% in the fed state). It was therefore largely replaced in clinical use by a soft gel capsule formulation (saquinavir-S Fortovase), in which absorption was increased approximately threefold. However, reformulation of saquinavir-H for once-daily dosing in combination with low-dose ritonavir (see Ritonavir) has both improved antiviral efficacy and decreased the gastrointestinal side effects typically associated with saquinavir-S. Moreover, coadministration of saquinavir-H with ritonavir results in blood levels of saquinavir similar to those associated with saquinavir-S, thus capitalizing on the pharmacokinetic interaction of the two agents. 

Hoke GD, Draper K, Freier SM, et al. Effect of phosphorothioate capping on antisense oligonucleotide stability, hybridization and antiviral efficacy versus herpes simplex virus infection, Nucleic Acid Res 1991 20 5743-5748. 

DIDANOSINE TENOFOVIR Possibly t adverse effects, including pancreatitis, lactic acidosis and neuropathy t plasma levels of didanosine additive effects Co-administration not recommended. Monitor closely for antiviral efficacy and side-effects (pancreatitis, neuropathy, lactic acidosis, renal failure). Not recommended in patients with a high viral load and low CD4 count (enteric-coated and buffered tablets), i dose of didanosine to 250 mg has been tried. Do not use in combination as triple therapy with lamivudine as there is a high level of treatment failure... 

Anti-HIV-1 Activity of Calanolides in Hollow Fiber Mouse Evaluation of (-l-)-calanolide A (1) in a hollow fiber culture-based in a SCID mouse assay of antiviral efficacy indicated that (+)-calanolide A exhibited significant anti-HIV-1 activity after oral or parenteral administration on a once-daily (200mg/kg/ dose) or twice-daily (150 mg/kg/dose) treatment. Furthermore, a synergistic effect was observed in the combination of (-l-)-calanolide A and AZT. ... 

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