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Discovery of Synergistic and Antagonistic Drug Combinations against SARS-CoV-2 In Vitro by Bobrowski, Tesia ;Chen, Lu ;Eastman, Richard T. ;Itkin, Zina ;Shinn, Paul ;Chen, Catherine ;Guo, Hui ;Zheng, Wei ;Michael, Sam ;Simeonov, Anton ;Hall, Matthew D. ;Zakharov, Alexey V. ;Muratov, Eugene N. is a scholarly article available to read on EtoBox.

What is Discovery of Synergistic and Antagonistic Drug Combinations against SARS-CoV-2 In Vitro about?

COVID-19 is undoubtedly the most impactful viral disease of the current century, afflicting millions worldwide. As yet, there is not an approved vaccine, as well as limited options from existing drugs for treating this disease. We hypothesized that combining drugs with independent mechanisms of action could result in synergy against SARS-CoV-2. Using __in silico__ approaches, we prioritized 73 combinations of 32 drugs with potential activity against SARS-CoV-2 and then tested them __in vitro__. Overall, we identified 16 synergistic and 8 antagonistic combinations, 4 of which were both synergistic and antagonistic in a dose-dependent manner. Among the 16 synergistic cases, combinations of nitazoxanide with three other compounds (remdesivir, amodiaquine and umifenovir) were the most notable, all exhibiting significant synergy against SARS-CoV-2. The combination of nitazoxanide, an FDA-approved drug, and remdesivir, FDA emergency use authorization for the treatment of COVID-19, demonstrate a strong synergistic interaction. Notably, the combination of remdesivir and hydroxychloroquine demonstrated strong antagonism. Overall, our results emphasize the importance of both drug repurposing

Author

Bobrowski, Tesia ;Chen, Lu ;Eastman, Richard T. ;Itkin, Zina ;Shinn, Paul ;Chen, Catherine ;Guo, Hui ;Zheng, Wei ;Michael, Sam ;Simeonov, Anton ;Hall, Matthew D. ;Zakharov, Alexey V. ;Muratov, Eugene N.

Publisher

Cold Spring Harbor Laboratory

Published

2020

Language

EN