Synergistic and Antagonistic Drug Combinations against SARS-CoV-2.

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

Molecular therapy : the journal of the American Society of Gene Therapy 2021 Feb 03

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Antiviral drug development for coronavirus disease 2019 (COVID-19) is occurring at an unprecedented pace, yet there are still limited therapeutic options for treating this disease. We hypothesized that combining drugs with independent mechanisms of action could result in synergy against SARS-CoV-2, thus generating better antiviral efficacy. Using in silico approaches, we prioritized 73 combinations of 32 drugs with potential activity against SARS-CoV-2 and then tested them in vitro. Sixteen synergistic and eight antagonistic combinations were identified; among 16 synergistic cases, combinations of the US Food and Drug Administration (FDA)-approved drug nitazoxanide with remdesivir, amodiaquine, or umifenovir were most notable, all exhibiting significant synergy against SARS-CoV-2 in a cell model. However, the combination of remdesivir and lysosomotropic drugs, such as hydroxychloroquine, demonstrated strong antagonism. Overall, these results highlight the utility of drug repurposing and preclinical testing of drug combinations for discovering potential therapies to treat COVID-19. Copyright © 2020 The American Society of Gene and Cell Therapy. All rights reserved.

Citation

Tesia Bobrowski, Lu Chen, Richard T Eastman, Zina Itkin, Paul Shinn, Catherine Z Chen, Hui Guo, Wei Zheng, Sam Michael, Anton Simeonov, Matthew D Hall, Alexey V Zakharov, Eugene N Muratov. Synergistic and Antagonistic Drug Combinations against SARS-CoV-2. Molecular therapy : the journal of the American Society of Gene Therapy. 2021 Feb 03;29(2):873-885