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Viruses 2018, 10(1), 48; https://doi.org/10.3390/v10010048

Verdinexor Targeting of CRM1 is a Promising Therapeutic Approach against RSV and Influenza Viruses

Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA
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Received: 9 December 2017 / Revised: 15 January 2018 / Accepted: 17 January 2018 / Published: 21 January 2018
(This article belongs to the Special Issue Viruses and Inflammation)
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Abstract

Two primary causes of respiratory tract infections are respiratory syncytial virus (RSV) and influenza viruses, both of which remain major public health concerns. There are a limited number of antiviral drugs available for the treatment of RSV and influenza, each having limited effectiveness and each driving selective pressure for the emergence of drug-resistant viruses. Novel broad-spectrum antivirals are needed to circumvent problems with current disease intervention strategies, while improving the cytokine-induced immunopathology associated with RSV and influenza infections. In this review, we examine the use of Verdinexor (KPT-335, a novel orally bioavailable drug that functions as a selective inhibitor of nuclear export, SINE), as an antiviral with multifaceted therapeutic potential. KPT-335 works to (1) block CRM1 (i.e., Chromosome Region Maintenance 1; exportin 1 or XPO1) mediated export of viral proteins critical for RSV and influenza pathogenesis; and (2) repress nuclear factor κB (NF-κB) activation, thus reducing cytokine production and eliminating virus-associated immunopathology. The repurposing of SINE compounds as antivirals shows promise not only against RSV and influenza virus but also against other viruses that exploit the nucleus as part of their viral life cycle. View Full-Text
Keywords: Chromosome Region Maintenance 1; Influenza; Respiratory syncytial virus; Verdinexor; KPT-335; antiviral Chromosome Region Maintenance 1; Influenza; Respiratory syncytial virus; Verdinexor; KPT-335; antiviral
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Pickens, J.A.; Tripp, R.A. Verdinexor Targeting of CRM1 is a Promising Therapeutic Approach against RSV and Influenza Viruses. Viruses 2018, 10, 48.

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