Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than two million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies t...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-02-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/13/2/271 |
| _version_ | 1797412036046487552 |
|---|---|
| author | Allison Bakovic Kenneth Risner Nishank Bhalla Farhang Alem Theresa L. Chang Warren K. Weston Jane A. Harness Aarthi Narayanan |
| author_facet | Allison Bakovic Kenneth Risner Nishank Bhalla Farhang Alem Theresa L. Chang Warren K. Weston Jane A. Harness Aarthi Narayanan |
| author_sort | Allison Bakovic |
| collection | DOAJ |
| description | Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than two million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options. In this manuscript, we describe the potent antiviral activity exerted by brilacidin—a de novo designed synthetic small molecule that captures the biological properties of HDPs—on SARS-CoV-2 in a human lung cell line (Calu-3) and a monkey cell line (Vero). These data suggest that SARS-CoV-2 inhibition in these cell culture models is likely to be a result of the impact of brilacidin on viral entry and its disruption of viral integrity. Brilacidin demonstrated synergistic antiviral activity when combined with remdesivir. Collectively, our data demonstrate that brilacidin exerts potent inhibition of SARS-CoV-2 against different strains of the virus in cell culture. |
| first_indexed | 2024-03-09T04:55:09Z |
| format | Article |
| id | doaj.art-803f44d235db4756ae657a1bf4608d5e |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T04:55:09Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-803f44d235db4756ae657a1bf4608d5e2023-12-03T13:06:41ZengMDPI AGViruses1999-49152021-02-0113227110.3390/v13020271Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell CultureAllison Bakovic0Kenneth Risner1Nishank Bhalla2Farhang Alem3Theresa L. Chang4Warren K. Weston5Jane A. Harness6Aarthi Narayanan7National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USANational Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USANational Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USANational Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USAPublic Health Research Institute, Rutgers, New Jersey Medical School, The State University of New Jersey, Newark, NJ 07103, USAInnovation Pharmaceuticals Inc., Wakefield, MA 01880, USAInnovation Pharmaceuticals Inc., Wakefield, MA 01880, USANational Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USASevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than two million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options. In this manuscript, we describe the potent antiviral activity exerted by brilacidin—a de novo designed synthetic small molecule that captures the biological properties of HDPs—on SARS-CoV-2 in a human lung cell line (Calu-3) and a monkey cell line (Vero). These data suggest that SARS-CoV-2 inhibition in these cell culture models is likely to be a result of the impact of brilacidin on viral entry and its disruption of viral integrity. Brilacidin demonstrated synergistic antiviral activity when combined with remdesivir. Collectively, our data demonstrate that brilacidin exerts potent inhibition of SARS-CoV-2 against different strains of the virus in cell culture.https://www.mdpi.com/1999-4915/13/2/271brilacidincoronavirusantiviraldefensinpeptidomimeticentry inhibition |
| spellingShingle | Allison Bakovic Kenneth Risner Nishank Bhalla Farhang Alem Theresa L. Chang Warren K. Weston Jane A. Harness Aarthi Narayanan Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture Viruses brilacidin coronavirus antiviral defensin peptidomimetic entry inhibition |
| title | Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture |
| title_full | Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture |
| title_fullStr | Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture |
| title_full_unstemmed | Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture |
| title_short | Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture |
| title_sort | brilacidin demonstrates inhibition of sars cov 2 in cell culture |
| topic | brilacidin coronavirus antiviral defensin peptidomimetic entry inhibition |
| url | https://www.mdpi.com/1999-4915/13/2/271 |
| work_keys_str_mv | AT allisonbakovic brilacidindemonstratesinhibitionofsarscov2incellculture AT kennethrisner brilacidindemonstratesinhibitionofsarscov2incellculture AT nishankbhalla brilacidindemonstratesinhibitionofsarscov2incellculture AT farhangalem brilacidindemonstratesinhibitionofsarscov2incellculture AT theresalchang brilacidindemonstratesinhibitionofsarscov2incellculture AT warrenkweston brilacidindemonstratesinhibitionofsarscov2incellculture AT janeaharness brilacidindemonstratesinhibitionofsarscov2incellculture AT aarthinarayanan brilacidindemonstratesinhibitionofsarscov2incellculture |