Niclosamide analog JMX0207 inhibits viral infectivity, viral RNA replication, and viral protein expression, and is a broad-spectrum antiviral for flaviviruses.
Background:
Previously we identified niclosamide as a broad-spectrum inhibitor for flaviviruses by targeting the interface between viral protease NS3 and its cofactor NS2B. Subsequently researchers screened a small library of niclosamide derivatives and identified a new analogue with improved pharmacokinetic properties. Compound JMX0207 showed improved efficacy in inhibition of the molecular interaction between NS3 and NS2B, better inhibition of viral protease function, and enhanced antiviral efficacy in the cell-based antiviral assay. The derivative also significantly reduced Zika virus infection on 3D mini-brain organoids derived from pluripotent neural stem cells. Intriguingly, the compound significantly reduced viremia in a Zika virus (ZIKV) animal model. In summary, a niclosamide derivative, JMX0207, was identified, which shows improved pharmacokinetics and efficacy against Zika virus both in vitro and in vivo.
Applications:
- Treatment of flavivirus’s including Zika
- Potential prophylactic use to prevent replication of a flavivirus.
Advantages:
Niclosamide also exhibits the ability to inhibit viral replication in a variety of viruses, including SARS [21], MERS-CoV [22], SARS-CoV-2 [23,24], and human adenovirus [26]
Niclosamide has applications in cancer that may strengthen the business case for development or co-development of analogs.
Patents and Licensing:
US Patent Application No.: 17/384,051
U.S. Patent Number 11,767,303 “Compounds And Methods for Inhibiting Viral Replication and Methods Of Treating and Preventing Flaviviral Infections”
Key Words:
Zika, Dengue virus, West Nile virus, Japanese encephalitis virus, Yellow fever virus, St. Louis encephalitis virus, Powassan virus, niclosamide, reformulation, Tick-Borne Encephalitis Virus, novel therapeutics, antiviral, protease inhibitor
References:
JMX0207, a Niclosamide Derivative with Improved Pharmacokinetics, Suppresses Zika Virus Infection Both In Vitro and In Vivo Zhong Li, Jimin Xu, Yuekun Lang, et al Hongmin Li ACS Infectious Diseases 2020 6 (10), 2616-2628 DOI: 10.1021/acsinfecdis.0c00217
Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential Jimin Xu, Pei-Yong Shi, Hongmin Li, and Jia Zhou ACS Infectious Diseases 2020 6 (5), 909-915 DOI: 10.1021/acsinfecdis.0c00052
Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction. Li, Z., Brecher, M., Deng, YQ. et al. Cell Res 27, 1046–1064 (2017). https://doi.org/10.1038/cr.2017.88
Contact :
Robert Gallo
Director Intellectual Property & Licensing
(1) 518-431-1208
robert.gallo@healthresearch.org