The effectiveness of antiviral agents with broad-spectrum activity against chikungunya virus varies between host cell lines.

Chikungunya virus (CHIKV) is a mosquito-borne virus that has recently emerged in the Western Hemisphere. Approved antiviral therapies or vaccines for the treatment or prevention of CHIKV infections are not available. This study aims to evaluate the antiviral activity of commercially available broad-spectrum antivirals against CHIKV.

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.

Sofosbuvir (SOF) Suppresses Ledipasvir (LDV)-resistant Mutants during SOF/LDV Combination Therapy against Genotype 1b Hepatitis C Virus (HCV).

Our objective was to identify drug interactions between ledipasvir (LDV) and sofosbuvir (SOF) against a genotype 1b replicon to determine optimal exposures for each agent that will maximize antiviral activity against susceptible and drug-resistant subpopulations. LDV and SOF were evaluated using a fully factorial experimental design in the BelloCell system. Replicon levels and drug-resistant variants were quantified at various times post-therapy for 14 days and a high-dimensional mathematical model was fit to the data.

Searching for synergy: Identifying optimal antiviral combination therapy using Hepatitis C virus (HCV) agents in a replicon system.

Direct acting antiviral agents (DAAs) are potent inhibitors of Hepatitis C virus (HCV) that have revolutionized the treatment landscape for this important viral disease. There are currently four classes of DAAs that inhibit HCV replication via distinct mechanisms of action: nonstructural protein (NS) 3/4a protease inhibitors, NS5A inhibitors, NS5B nucleoside polymerase inhibitors, and NS5B non-nucleoside polymerase inhibitors. Combination therapy with two or more DAAs has great potential to further enhance antiviral potency.

Preclinical Evaluations To Identify Optimal Linezolid Regimens for Tuberculosis Therapy.

Unlabelled: Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis.

Pharmacodynamic evaluation of the activities of six parenteral vancomycin products available in the United States.

A recent report found that generic parenteral vancomycin products may not have in vivo efficacies equivalent to those of the innovator in a neutropenic murine thigh infection model despite having similar in vitro microbiological activities and murine serum pharmacokinetics. We compared the in vitro and in vivo activities of six of the parenteral vancomycin products available in the United States. The in vitro assessments for the potencies of the vancomycin products included MIC/minimal bactericidal concentration (MBC) determinations, quantifying the impact of human and murine serum on the MIC values, and time-kill studies.

Interaction of drug- and granulocyte-mediated killing of Pseudomonas aeruginosa in a murine pneumonia model.

Background: Killing of bacterial pathogens by granulocytes is a saturable process, as previously demonstrated. There is virtually no quantitative information about how granulocytes interact with antimicrobial chemotherapy to kill bacterial cells.

Methods: We performed a dose-ranging study with the aminoglycoside plazomicin against Pseudomonas aeruginosa ATCC27853 in a granulocyte-replete murine pneumonia model.