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Anti-histamine drug Clarinex can kill Borrelia by interfering with manganese utilization

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Borreliacidal activity of Borrelia metal transporter A (BmtA) binding small molecules by manganese transport inhibition
 
Abstract:
 
Background: Borrelia burgdorferi, the causative agent of Lyme disease, utilizes manganese (Mn) for its various metabolic needs. We hypothesized that blocking Mn transporter could be a possible approach to inhibit metabolic activity of this pathogen and eliminate the infection.
 
Methods: We used a combination of in silico protein structure prediction together with molecular docking to target the Borrelia metal transporter A (BmtA), a single known Mn transporter in Borrelia and screened libraries of FDA approved compounds that could potentially bind to the predicted BmtA structure with high affinity. Tricyclic antihistamines such as loratadine, desloratadine, and 3-hydroxydesloratadine as well as yohimbine and tadalafil demonstrated a tight binding to the in silico folded BmtA transporter. We, then tested borreliacidal activity and dose response of the shortlisted compounds from this screen using a series of in vitro assays.
 
Results: Amongst the probed compounds, desloratadine exhibited potent borreliacidal activity in vitro at and above 78 µg/mL (250 µM). Borrelia treated with lethal doses of desloratadine exhibited a significant loss of intracellular Mn specifically and a severe structural damage to the bacterial cell wall.
 
Conclusion: Our results support the possibility of developing a novel, targeted therapy to treat Lyme disease by targeting specific metabolic needs of Borrelia.
 
Source:  Dove Press, February 2015 Volume 2015:9 Pages 805—816.  By Wagh D, Pothineni VR, Inayathullah M, Liu S, Kim KM, Rajadas.  Biomaterials and Advanced Drug Delivery Laboratory, Stanford Cardiovascular Pharmacology Division, Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA, USA.

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One thought on “Anti-histamine drug Clarinex can kill Borrelia by interfering with manganese utilization”

  1. marsmagda says:

    I’m little confused . I read the article and the study and from what I understand chemical Desloratadine was most potent in destroying cell wall .
    Title states that Claritin can kill borrelia bacteria . Claritin contains Loratadine not Desloratadine .
    Medication Clarinex not Claritin contains Desloratadine .
    Desloratadine (Clarinex) is an active metabolite of Loratadine (Claritin)

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