Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model.

Sahar Alsaidi,José A Fernández Romero,Oneil Mahoney,Theresa Chang,Neeharika Verma,James Sailer,Thierry Bonnaire,Nadjet Cornejal,Barry R O’Keefe,Thomas M Zydowsky,Claudia Melo,Natalia Teleshova

doi:10.3390/md19080418

Abstract

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 (CC50) and half-maximal effective concentration (EC50) 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 = CC50/EC50) 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 (EC50 between 3.2 and 7.5 µg/mL). Carrageenan and griffithsin combinations exhibited synergistic activity (EC50 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.

Highlights

Licensee MDPI, Basel, Switzerland.The emergence of a novel coronavirus, quickly escalated into the current pandemic that was declared on 11 March 2020, by the World Health Organization
We focused on ι-CG and λ-CG, evaluating their combination with GRFT
These results strongly suggest that a GRFT/CG combination could provide broadspectrum antiviral activity targeting different respiratory viruses, including a range of coronaviruses

Summary

Introduction

The emergence of a novel coronavirus, quickly escalated into the current pandemic that was declared on 11 March 2020, by the World Health Organization. The novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the Coronaviridae family. This family includes SARS-CoV-1 and MERS-CoV, two zoonotic. Highly effective vaccines targeting SARS-CoV-2 spike proteins have been approved for emergency use by multiple stringent regulatory authorities, accumulation of mutations in the spike protein may allow the virus to be transmitted more effectively and, in the worst-case scenario, evade the immune response triggered by vaccines [3,4,5,6]

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Results

Conclusion