Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model
Over 182 million confirmed cases of COVID-19 and more than 4 million deaths have been reported to date around the world. It is essential to identify broad-spectrum antiviral agents that may prevent or treat infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also by other...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/19/8/418 |
| _version_ | 1827684875745886208 |
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| author | Sahar Alsaidi Nadjet Cornejal Oneil Mahoney Claudia Melo Neeharika Verma Thierry Bonnaire Theresa Chang Barry R. O’Keefe James Sailer Thomas M. Zydowsky Natalia Teleshova José A. Fernández Romero |
| author_facet | Sahar Alsaidi Nadjet Cornejal Oneil Mahoney Claudia Melo Neeharika Verma Thierry Bonnaire Theresa Chang Barry R. O’Keefe James Sailer Thomas M. Zydowsky Natalia Teleshova José A. Fernández Romero |
| author_sort | Sahar Alsaidi |
| collection | DOAJ |
| description | Over 182 million confirmed cases of COVID-19 and more than 4 million deaths have been reported to date around the world. It is essential to identify broad-spectrum antiviral agents that may prevent or treat infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also by other coronaviruses that may jump the species barrier in the future. We evaluated the antiviral selectivity of griffithsin and sulfated and non-sulfated polysaccharides against SARS-CoV-1 and SARS-CoV-2 using a cytotoxicity assay and a cell-based pseudoviral model. The half-maximal cytotoxic concentration (CC<sub>50</sub>) and half-maximal effective concentration (EC<sub>50</sub>) were determined for each compound, using a dose-response-inhibition analysis on GraphPad Prism v9.0.2 software (San Diego, CA, USA). The therapeutic index (TI = CC<sub>50</sub>/EC<sub>50</sub>) was calculated for each compound. The potential synergistic, additive, or antagonistic effect of different compound combinations was determined by CalcuSyn v1 software (Biosoft, Cambridge, UK), which estimated the combination index (CI) values. Iota and lambda carrageenan showed the most potent antiviral activity (EC<sub>50</sub> between 3.2 and 7.5 µg/mL). Carrageenan and griffithsin combinations exhibited synergistic activity (EC<sub>50</sub> between 0.2 and 3.8 µg/mL; combination index <1), including against recent SARS-CoV-2 mutations. The griffithsin and carrageenan combination is a promising candidate to prevent or treat infections by SARS-CoV-1 and SARS-CoV-2. |
| first_indexed | 2024-03-10T08:39:19Z |
| format | Article |
| id | doaj.art-a04caab404de4d3fa775e6b37537f43f |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T08:39:19Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-a04caab404de4d3fa775e6b37537f43f2023-11-22T08:25:21ZengMDPI AGMarine Drugs1660-33972021-07-0119841810.3390/md19080418Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral ModelSahar Alsaidi0Nadjet Cornejal1Oneil Mahoney2Claudia Melo3Neeharika Verma4Thierry Bonnaire5Theresa Chang6Barry R. O’Keefe7James Sailer8Thomas M. Zydowsky9Natalia Teleshova10José A. Fernández Romero11Population Council, New York, NY 10065, USAPopulation Council, New York, NY 10065, USAPopulation Council, New York, NY 10065, USAPopulation Council, New York, NY 10065, USAPopulation Council, New York, NY 10065, USAPopulation Council, New York, NY 10065, USADepartment of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07102, USANatural Products Branch, Molecular Targets Program, Developmental Therapeutics Program, Center for Cancer Research, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD 21702, USAPopulation Council, New York, NY 10065, USAPopulation Council, New York, NY 10065, USAPopulation Council, New York, NY 10065, USAPopulation Council, New York, NY 10065, USAOver 182 million confirmed cases of COVID-19 and more than 4 million deaths have been reported to date around the world. It is essential to identify broad-spectrum antiviral agents that may prevent or treat infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also by other coronaviruses that may jump the species barrier in the future. We evaluated the antiviral selectivity of griffithsin and sulfated and non-sulfated polysaccharides against SARS-CoV-1 and SARS-CoV-2 using a cytotoxicity assay and a cell-based pseudoviral model. The half-maximal cytotoxic concentration (CC<sub>50</sub>) and half-maximal effective concentration (EC<sub>50</sub>) were determined for each compound, using a dose-response-inhibition analysis on GraphPad Prism v9.0.2 software (San Diego, CA, USA). The therapeutic index (TI = CC<sub>50</sub>/EC<sub>50</sub>) was calculated for each compound. The potential synergistic, additive, or antagonistic effect of different compound combinations was determined by CalcuSyn v1 software (Biosoft, Cambridge, UK), which estimated the combination index (CI) values. Iota and lambda carrageenan showed the most potent antiviral activity (EC<sub>50</sub> between 3.2 and 7.5 µg/mL). Carrageenan and griffithsin combinations exhibited synergistic activity (EC<sub>50</sub> between 0.2 and 3.8 µg/mL; combination index <1), including against recent SARS-CoV-2 mutations. The griffithsin and carrageenan combination is a promising candidate to prevent or treat infections by SARS-CoV-1 and SARS-CoV-2.https://www.mdpi.com/1660-3397/19/8/418SARS-CoV-1SARS-CoV-2lectinssulfated polysaccharides |
| spellingShingle | Sahar Alsaidi Nadjet Cornejal Oneil Mahoney Claudia Melo Neeharika Verma Thierry Bonnaire Theresa Chang Barry R. O’Keefe James Sailer Thomas M. Zydowsky Natalia Teleshova José A. Fernández Romero Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model Marine Drugs SARS-CoV-1 SARS-CoV-2 lectins sulfated polysaccharides |
| title | Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model |
| title_full | Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model |
| title_fullStr | Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model |
| title_full_unstemmed | Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model |
| title_short | Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model |
| title_sort | griffithsin and carrageenan combination results in antiviral synergy against sars cov 1 and 2 in a pseudoviral model |
| topic | SARS-CoV-1 SARS-CoV-2 lectins sulfated polysaccharides |
| url | https://www.mdpi.com/1660-3397/19/8/418 |
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