Broad-spectrum virucidal activity of (NVC-422) N,N-dichloro-2,2-dimethyltaurine against viral ocular pathogens in vitro.

نویسندگان

  • Andreas Jekle
  • Suriani Abdul Rani
  • Chris Celeri
  • Meghan Zuck
  • Ping Xu
  • Lu Wang
  • Kathryn Najafi-Tagol
  • Mark Anderson
  • David Stroman
  • Dmitri Debabov
چکیده

PURPOSE Viral conjunctivitis is a highly contagious infection often causing major epidemics. A safe broad-spectrum antiviral agent is needed to treat this unmet medical need. The purpose of this study is to demonstrate that in vitro NVC-422 is a safe, broad-spectrum topical virucidal agent with activity against ophthalmic viral pathogens. METHODS The virucidal activity of NVC-422 against several serotypes of human adenovirus (HAdV), coxsackievirus A24, enterovirus 70, and herpes simplex-virus-1 (HSV-1) was tested in standard in vitro titer reduction assays with or without tears. An in vitro irritancy score for NVC-422 was determined using the MatTek EpiOcular tissue system. RESULTS NVC-422 reduced the viral titer of HAdV-5, HAdV-8, HAdV-19, HAdV-37, and HSV-1 by at least 4 logs after 1 hour incubation at 250 μM. Incubation of coxsackievirus A24 and enterovirus 70 with 2.5 mM NVC-422 for 1 hour reduced the viral titer by 4 logs and 4.5 logs, respectively. The virucidal activity of NVC-422 is maintained in the presence of 10% synthetic tears. In the EpiOcular corneal tissue model, NVC-422 was nonirritating at concentrations up to 41 mM. CONCLUSIONS NVC-422 has potent, rapid in vitro virucidal activity against major causes of conjunctivitis. Its broad-spectrum virucidal activity combined with favorable safety profile validates NVC-422 as a potential new therapeutic agent against viral conjunctivitis.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Antimicrobial and anticoagulant activities of N-chlorotaurine, N,N-dichloro-2,2-dimethyltaurine, and N-monochloro-2,2-dimethyltaurine in human blood.

The aim of this study was to determine the potential application of N-chlorotaurine (NCT), N,N-dichloro-2,2-dimethyltaurine (NVC-422), and N-monochloro-2,2-dimethyltaurine (NVC-612) as catheter lock solutions for the prevention of catheter blockage and catheter-related bloodstream infections by testing their anticoagulant and broad-spectrum antimicrobial activities in human blood. NCT, NVC-422,...

متن کامل

Chemical characterization and biological properties of NVC-422, a novel, stable N-chlorotaurine analog.

During oxidative burst, neutrophils selectively generate HOCl to destroy invading microbial pathogens. Excess HOCl reacts with taurine, a semi-essential amino acid, resulting in the formation of the longer-lived biogenerated broad-spectrum antimicrobial agent, N-chlorotaurine (NCT). In the presence of an excess of HOCl or under moderately acidic conditions, NCT can be further chlorinated, or it...

متن کامل

N-chlorotaurine and its analogues N,N-dichloro-2,2-dimethyltaurine and N-monochloro-2,2-dimethyltaurine are safe and effective bactericidal agents in ex vivo corneal infection models.

PURPOSE N-chlorotaurine (NCT) and its analogues N-monochloro-2,2-dimethyltaurine (NVC-612) and N-dichloro-2,2-dimethyltaurine (NVC-422) are new anti-infectives for topical treatment for conjunctivitis. The aim of this study was to show that these compounds are safe in an EpiOcular model and effective in corneas infected ex vivo. METHODS Corneal buttons were excised from porcine eyes. In 183 o...

متن کامل

NVC-422 inactivates Staphylococcus aureus toxins.

Bacterial pathogens have specific virulence factors (e.g., toxins) that contribute significantly to the virulence and infectivity of microorganisms within the human hosts. Virulence factors are molecules expressed by pathogens that enable colonization, immunoevasion, and immunosuppression, obtaining nutrients from the host or gaining entry into host cells. They can cause pathogenesis by inhibit...

متن کامل

NVC-422 topical gel for the treatment of impetigo.

Impetigo is a highly contagious bacterial skin infection affecting children worldwide that is caused by the Gram-positive bacteria Staphylococcus aureus, Streptococcus pyogenes, or both. Staphylococcus species can quickly develop drug resistance rendering mupirocin, fusidic acid, and erythromycin ineffective. Preclinical and clinical studies demonstrated that NVC-422 (N, N-dichloro-2, 2-dimethy...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Investigative ophthalmology & visual science

دوره 54 2  شماره 

صفحات  -

تاریخ انتشار 2013