Brilacidin, a Non-Peptide Defensin-Mimetic Molecule, Inhibits SARS-CoV-2 Infection by Blocking Viral Entry.

Brilacidin (PMX-30063), a non-peptide defensin-mimetic small molecule, inhibits SARS-CoV-2 viral infection but the anti-viral mechanism is not defined. Here we determined its effect on the specific step of the viral life cycle. Brilacidin blocked SARS-CoV-2 infection but had no effect after viral entry.

Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than two million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options.

The effects of sildenafil on human sperm function in healthy volunteers.

Aims: This double-blind, randomized, four-period, two-way crossover study was conducted to evaluate the acute effects of oral sildenafil (100-mg single dose) on sperm motility, count, density, morphology and vitality as well as ejaculate volume and viscosity in healthy male subjects. The concentrations of sildenafil and its primary circulating metabolite UK-103,320 were measured in ejaculate and compared with those in plasma. The study also included assessments of safety and tolerability.

The effects of steady-state erythromycin and azithromycin on the pharmacokinetics of sildenafil in healthy volunteers.

Aims: Sildenafil, an effective oral treatment for erectile dysfunction, is predominantly metabolized by the cytochrome P450 isozyme 3A4, which is inhibited by a number of the macrolide antibiotics. Therefore, two placebo-controlled, parallel-group studies were conducted to evaluate the effects of multiple doses of erythromycin and azithromycin on the pharmacokinetics, safety and tolerability of a single oral 100-mg dose of sildenafil.

Methods: In the erythromycin interaction study, 26 male volunteers (18--45 years of age) received open-label sildenafil 100 mg on day 1.

Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality.

Aims: To determine the absolute bioavailability, dose proportionality and the effects of food on the pharmacokinetics of single oral doses of sildenafil citrate.

Methods: Three open-label, randomized crossover studies were conducted in healthy male subjects. Absolute bioavailability was determined by comparing pharmacokinetic data after administration of single oral and intravenous 50-mg doses of sildenafil (n=12 subjects).