Brilacidin as a Broad-Spectrum Inhibitor of Enveloped, Acutely Infectious Viruses
Alphaviruses, belonging to the <i>Togaviridae</i> family, and bunyaviruses, belonging to the <i>Paramyxoviridae</i> family, are globally distributed and lack FDA-approved vaccines and therapeutics. The alphaviruses Venezuelan equine encephalitis virus (VEEV) and eastern equin...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
|
| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/12/1/54 |
| _version_ | 1797339642890027008 |
|---|---|
| author | Carol A. Anderson Michael D. Barrera Niloufar A. Boghdeh Miata Smith Farhang Alem Aarthi Narayanan |
| author_facet | Carol A. Anderson Michael D. Barrera Niloufar A. Boghdeh Miata Smith Farhang Alem Aarthi Narayanan |
| author_sort | Carol A. Anderson |
| collection | DOAJ |
| description | Alphaviruses, belonging to the <i>Togaviridae</i> family, and bunyaviruses, belonging to the <i>Paramyxoviridae</i> family, are globally distributed and lack FDA-approved vaccines and therapeutics. The alphaviruses Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV) are known to cause severe encephalitis, whereas Sindbis virus (SINV) causes arthralgia potentially persisting for years after initial infection. The bunyavirus Rift Valley Fever virus (RVFV) can lead to blindness, liver failure, and hemorrhagic fever. Brilacidin, a small molecule that was designed de novo based on naturally occurring host defensins, was investigated for its antiviral activity against these viruses in human small airway epithelial cells (HSAECs) and African green monkey kidney cells (Veros). This testing was further expanded into a non-enveloped Echovirus, a <i>Picornavirus</i>, to further demonstrate brilacidin’s effect on early steps of the viral infectious cycle that leads to inhibition of viral load. Brilacidin demonstrated antiviral activity against alphaviruses VEEV TC-83, VEEV TrD, SINV, EEEV, and bunyavirus RVFV. The inhibitory potential of brilacidin against the viruses tested in this study was dependent on the dosing strategy which necessitated compound addition pre- and post-infection, with addition only at the post-infection stage not eliciting a robust inhibitory response. The inhibitory activity of brilacidin was only modest in the context of the non-enveloped <i>Picornavirus</i> Echovirus, suggesting brilacidin may be less potent against non-enveloped viruses. |
| first_indexed | 2024-03-08T09:51:18Z |
| format | Article |
| id | doaj.art-cb7a8e009b614da98b4474863e5ffdd6 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-08T09:51:18Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-cb7a8e009b614da98b4474863e5ffdd62024-01-29T14:05:52ZengMDPI AGMicroorganisms2076-26072023-12-011215410.3390/microorganisms12010054Brilacidin as a Broad-Spectrum Inhibitor of Enveloped, Acutely Infectious VirusesCarol A. Anderson0Michael D. Barrera1Niloufar A. Boghdeh2Miata Smith3Farhang Alem4Aarthi Narayanan5Center for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USACenter for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USACenter for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USACenter for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USACenter for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USACenter for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USAAlphaviruses, belonging to the <i>Togaviridae</i> family, and bunyaviruses, belonging to the <i>Paramyxoviridae</i> family, are globally distributed and lack FDA-approved vaccines and therapeutics. The alphaviruses Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV) are known to cause severe encephalitis, whereas Sindbis virus (SINV) causes arthralgia potentially persisting for years after initial infection. The bunyavirus Rift Valley Fever virus (RVFV) can lead to blindness, liver failure, and hemorrhagic fever. Brilacidin, a small molecule that was designed de novo based on naturally occurring host defensins, was investigated for its antiviral activity against these viruses in human small airway epithelial cells (HSAECs) and African green monkey kidney cells (Veros). This testing was further expanded into a non-enveloped Echovirus, a <i>Picornavirus</i>, to further demonstrate brilacidin’s effect on early steps of the viral infectious cycle that leads to inhibition of viral load. Brilacidin demonstrated antiviral activity against alphaviruses VEEV TC-83, VEEV TrD, SINV, EEEV, and bunyavirus RVFV. The inhibitory potential of brilacidin against the viruses tested in this study was dependent on the dosing strategy which necessitated compound addition pre- and post-infection, with addition only at the post-infection stage not eliciting a robust inhibitory response. The inhibitory activity of brilacidin was only modest in the context of the non-enveloped <i>Picornavirus</i> Echovirus, suggesting brilacidin may be less potent against non-enveloped viruses.https://www.mdpi.com/2076-2607/12/1/54alphavirusbunyavirusEchovirustherapeuticsmall moleculeviral envelope |
| spellingShingle | Carol A. Anderson Michael D. Barrera Niloufar A. Boghdeh Miata Smith Farhang Alem Aarthi Narayanan Brilacidin as a Broad-Spectrum Inhibitor of Enveloped, Acutely Infectious Viruses Microorganisms alphavirus bunyavirus Echovirus therapeutic small molecule viral envelope |
| title | Brilacidin as a Broad-Spectrum Inhibitor of Enveloped, Acutely Infectious Viruses |
| title_full | Brilacidin as a Broad-Spectrum Inhibitor of Enveloped, Acutely Infectious Viruses |
| title_fullStr | Brilacidin as a Broad-Spectrum Inhibitor of Enveloped, Acutely Infectious Viruses |
| title_full_unstemmed | Brilacidin as a Broad-Spectrum Inhibitor of Enveloped, Acutely Infectious Viruses |
| title_short | Brilacidin as a Broad-Spectrum Inhibitor of Enveloped, Acutely Infectious Viruses |
| title_sort | brilacidin as a broad spectrum inhibitor of enveloped acutely infectious viruses |
| topic | alphavirus bunyavirus Echovirus therapeutic small molecule viral envelope |
| url | https://www.mdpi.com/2076-2607/12/1/54 |
| work_keys_str_mv | AT carolaanderson brilacidinasabroadspectruminhibitorofenvelopedacutelyinfectiousviruses AT michaeldbarrera brilacidinasabroadspectruminhibitorofenvelopedacutelyinfectiousviruses AT niloufaraboghdeh brilacidinasabroadspectruminhibitorofenvelopedacutelyinfectiousviruses AT miatasmith brilacidinasabroadspectruminhibitorofenvelopedacutelyinfectiousviruses AT farhangalem brilacidinasabroadspectruminhibitorofenvelopedacutelyinfectiousviruses AT aarthinarayanan brilacidinasabroadspectruminhibitorofenvelopedacutelyinfectiousviruses |