Antiviral Evaluation of UV-4B and Interferon-Alpha Combination Regimens against Dengue Virus.

Dengue virus (DENV) is a flavivirus associated with clinical manifestations ranging in severity from self-limiting dengue fever, to the potentially life threatening condition, severe dengue. There are currently no approved antiviral therapies for the treatment of DENV. Here, we evaluated the antiviral potential of four broad-spectrum antivirals, UV-4B, interferon-alpha (IFN), sofosbuvir (SOF), and favipiravir (FAV) against DENV serotype 2 as mono- and combination therapy in cell lines that are physiologically relevant to human infection.

Microphysiological heart-liver body-on-a-chip system with a skin mimic for evaluating topical drug delivery.

Body-on-a-chip in vitro systems are a promising technology that aims to increase the predictive power of drug efficacy and toxicity in humans when compared to traditional animal models. Here, we developed a new heart-liver body-on-a-chip system with a skin surrogate to assess the toxicity of drugs that are topically administered. In order to test the utility of the system, diclofenac, ketoconazole, hydrocortisone and acetaminophen were applied topically through a synthetic skin surrogate (Strat-M membrane) and the toxicity results were compared to those of acute drug exposure from systemically applying the compounds.

A human-on-a-chip approach to tackling rare diseases.

Drug development for rare diseases, classified as diseases with a prevalence of < 200 000 patients, is limited by the high cost of research and low target population. Owing to a lack of representative disease models, research has been challenging for orphan drugs. Human-on-a-chip (HoaC) technology, which models human tissues in interconnected in vitro microfluidic devices, has the potential to lower the cost of preclinical studies and increase the rate of drug approval by introducing human phenotypic models early in the drug discovery process.

Clinical Regimens of Favipiravir Inhibit Zika Virus Replication in the Hollow-Fiber Infection Model.

Zika virus (ZIKV) infection is associated with serious, long-term neurological manifestations. There are currently no approved therapies for the treatment or prevention of ZIKV infection. Favipiravir (FAV) is a viral polymerase inhibitor with broad-spectrum activity.

Antiviral Effects of Clinically-Relevant Interferon-α and Ribavirin Regimens against Dengue Virus in the Hollow Fiber Infection Model (HFIM).

Dengue virus (DENV) is the most prevalent mosquito-borne viral illness in humans. Currently, there are no therapeutic agents available to prevent or treat DENV infections. Our objective was to fill this unmet medical need by evaluating the antiviral activity of interferon-α (IFN) and ribavirin (RBV) as a combination therapy against DENV.

Zika Virus Replication Is Substantially Inhibited by Novel Favipiravir and Interferon Alpha Combination Regimens.

Zika virus (ZIKV) is a major public health concern due to its overwhelming spread into the Americas. Currently, there are neither licensed vaccines nor antiviral therapies available for the treatment of ZIKV. We aimed to identify and rationally optimize effective therapeutic regimens for ZIKV by evaluating the antiviral potentials of the approved broad-spectrum antiviral agents favipiravir (FAV), interferon alpha (IFN), and ribavirin (RBV) as single agents and in combinations.

Oseltamivir-zanamivir combination therapy suppresses drug-resistant H1N1 influenza A viruses in the hollow fiber infection model (HFIM) system.

Drug-resistant influenza is a significant threat to global public health. Until new antiviral agents with novel mechanisms of action become available, there is a pressing need for alternative treatment strategies with available influenza antivirals. Our aims were to evaluate the antiviral activity of two neuraminidase inhibitors (oseltamivir and zanamivir) as combination therapy against H1N1 influenza A viruses, as these agents bind to the neuraminidase active site differently: oseltamivir requires a conformational change for binding whereas zanamivir does not.

Aminomethylnaphthoquinones and HSV-1: in vitro and in silico evaluations of potential antivirals.

Background: Herpes simplex viruses (HSV) are leading causes of human infections which result in severe manifestations, especially in neonates, immunocompromised and/or transplanted individuals. Current HSV type-1 (HSV-1) resistance to standard antiviral agents is a therapeutic challenge, especially for treating immunocompromised patients.

Methods: Herein we describe the promising antiviral profile of three 2-aminomethyl-3-hydroxy-1,4-naphthoquinones against HSV-1 using Vero cells.

Herpes simplex virus type-1: replication, latency, reactivation and its antiviral targets.

Infection by herpes simplex virus type-1 (HSV-1) causes several diseases, ranging from cutaneous, oral and genital infections to fatal encephalitis. Despite the availability of antiviral therapies on the market, their efficacies are incomplete, and new cases of resistant strains arise, mainly in the immunocompromised, but also recently documented in immunocompetent patients. Over the last decades a lot has been discovered about the molecular basis of infection which has been of great benefit to the investigation of new anti-HSV-1 molecules.