Use of minocycline in viral infections

Kallol Dutta, Anirban Basu, Kallol Dutta, Anirban Basu

Abstract

Repurposing of old drugs is a useful concept as it helps to minimize costs associated with the research and development of a new drug. Minocycline, a common second generation antibiotic, has been shown to possess several other beneficial effects other than its intended uses. The antiviral role of minocycline has generated considerable interest from the last decade. It was first shown to be beneficial in preventing human immunodeficiency virus (HIV) infections and later it was reported to improve cognitive deficiencies associate with neuroAIDS. However, its antiviral efficacies are not limited to retroviruses alone. In animal models or in vitro systems of flaviviral infections (especially Japanese encephalitis virus), minocycline has been shown to be highly effective. However, not all effects are based on direct inhibition of viral replication. The general anti-inflammatory and immunomodulatory properties of minocycline are also responsible in part, in imparting the protective effects. Owing to the fact that minocycline is well tolerated by most people and that the drug has nearly 40 years history of usage, it is an exciting prospect to try out in other viral infections.

References

    1. Smilack JD. The tetracyclines. Mayo Clin Proc. 1999;74:727–9.
    1. Goulden V. Guidelines for the management of acne vulgaris in adolescents. Paediatr Drugs. 2003;5:301–13.
    1. Comprehensive Information on Prescription Drugs. (Updated: January 07, 2010) [accessed on June 18, 2010]. Available from: .
    1. Tilley BC, Alarcon GS, Heyse SP, Trentham DE, Neuner R, Kaplan DA, et al. Minocycline in rheumatoid arthritis.A 48-week, double-blind, placebo-controlled trial. MIRA Trial Group. Ann Intern Med . 1995;122:81–9.
    1. Gelber RH, Fukuda K, Byrd S, Murray LP, Siu P, Tsang M, et al. A clinical trial of minocycline in lepromatous leprosy. BMJ. 1992;304:91–2.
    1. Macdonald H, Kelly RG, Allen ES, Noble JF, Kanegis LA. Pharmacokinetic studies on minocycline in man. Clin Pharmacol Ther. 1973;14:852–61.
    1. Carney S, Butcher RA, Dawborn JK, Pattison G. Minocycline excretion and distribution in relation to renal function in man. Clin Exp Pharmacol Physiol. 1974;1:299–308.
    1. Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA. 1998;95:15769–74.
    1. Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, et al. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology. 2007;69:1404–10.
    1. Zabad RK, Metz LM, Todoruk TR, Zhang Y, Mitchell JR, Yeung M, et al. The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study. Mult Scler. 2007;13:517–26.
    1. Kwon BK, Okon E, Hillyer J, Mann C, Baptiste D, Weaver LC, et al. A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. J Neurotrauma. 2010 (In Press)
    1. Thomas M, Le WD. Minocycline: neuroprotective mechanisms in Parkinson's disease. Curr Pharm Des. 2004;10:679–86.
    1. Huntington Study Group. Minocycline safety and tolerability in Huntington disease. Neurology. 2004;63:547–9.
    1. Yong VW, Wells J, Giuliani F, Casha S, Power C, Metz LM. The promise of minocycline in neurology. Lancet Neurol. 2004;3:744–51.
    1. Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C, et al. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol. 2007;6:1045–53.
    1. . A service of the U.S. National Institutes of Health. Safety and Feasibility of Minocycline in the Treatment of Traumatic Brain Injury (TBI). (Updated: February 11, 2010) [accessed on June 21, 2010]. Available from: .
    1. . A service of the U.S. National Institutes of Health. Safety and Feasibility of Minocycline in the Treatment of Traumatic Brain Injury (TBI). (Updated: February 11, 2010) [accessed on June 21, 2010]. Available from: .
    1. . A service of the U.S. National Institutes of Health. Safety and Minocycline as an Adjunctive Therapy for Schizophrenia: a Randomized Controlled Study. (Updated: May 26, 2010) [accessed on June 21, 2010]. Available from: .
    1. Lemaitre M, Guetard D, Henin Y, Montagnier L, Zerial A. Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells. Res Virol. 1990;141:5–16.
    1. Si Q, Cosenza M, Kim MO, Zhao ML, Brownlee M, Goldstein H, et al. A novel action of minocycline: inhibition of human immunodeficiency virus type 1 infection in microglia. J Neurovirol. 2004;10:284–92.
    1. Zink MC, Uhrlaub J, DeWitt J, Voelker T, Bullock B, Mankowski J, et al. Neuroprotective and anti-human immunodeficiency virus activity of minocycline. JAMA. 2005;293:2003–11.
    1. Follstaedt SC, Barber SA, Zink MC. Mechanisms of minocycline-induced suppression of simian immunodeficiency virus encephalitis: inhibition of apoptosis signal-regulating kinase 1. J Neurovirol. 2008;14:376–88.
    1. Jenwitheesuk E, Samudrala R. Identification of potential HIV-1 targets of minocycline. Bioinformatics. 2007;23:2797–9.
    1. Szeto GL, Brice AK, Yang HC, Barber SA, Siliciano RF, Clements JE. Minocycline attenuates HIV infection and reactivation by suppressing cellular activation in human CD4+ T cells. J Infect Dis. 2010;201:1132–40.
    1. Ratai EM, Bombardier JP, Joo CG, Annamalai L, Burdo TH, Campbell J, et al. Proton magnetic resonance spectroscopy reveals neuroprotection by oral minocycline in a nonhuman primate model of accelerated NeuroAIDS. PLoS One. 2010;5:e10523.
    1. . A service of the U.S. National Institutes of Health. Minocycline for HIV+ Cognitive Impairment in Uganda. (Updated: May 26, 2010) [accessed on June 21, 2010]. Available from: .
    1. Michaelis M, Kleinschmidt MC, Doerr HW, Cinatl J., Jr Minocycline inhibits West Nile virus replication and apoptosis in human neuronal cells. J Antimicrob Chemother. 2007;60:981–6.
    1. Mishra MK, Basu A. Minocycline neuroprotects, reduces microglial activation, inhibits caspase 3 induction, and viral replication following Japanese encephalitis. J Neurochem. 2008;105:1582–95.
    1. Mishra MK, Ghosh D, Duseja R, Basu A. Antioxidant potential of minocycline in Japanese Encephalitis virus infection in murine neuroblastoma cells: correlation with membrane fluidity and cell death. Neurochem Int. 2009;54:464–70.
    1. Mishra MK, Dutta K, Saheb SK, Basu A. Understanding the molecular mechanism of blood-brain barrier damage in an experimental model of Japanese encephalitis: correlation with minocycline administration as a therapeutic agent. Neurochem Int. 2009;55:717–23.
    1. Clinical Trials Registry- India. A service of the Indian Council of Medical Research. Randomised Double Blind Controlled Trial of Minocycline in Japanese encephalitis. (Updated: January 11, 2011). [accessed on April 18, 2011]. Available from: .
    1. Irani DN, Prow NA. Neuroprotective interventions targeting detrimental host immune responses protect mice from fatal alphavirus encephalitis. J Neuropathol Exp Neurol. 2007;66:533–44.
    1. Richardson-Burns SM, Tyler KL. Minocycline delays disease onset and mortality in reovirus encephalitis. Exp Neurol. 2005;192:331–9.
    1. Chong CR, Sullivan DJ., Jr New uses for old drugs. Nature. 2007;448:645–6.

Source: PubMed

3
Iratkozz fel