Synergistic and Antagonistic Drug Combinations against SARS-CoV-2
Year: 2020
Type: article
Abstract: 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.
Source: Molecular Therapy
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,500
Awards: Biomedical Data Translator Technical Feasibility Assessment and Architecture Design, G2955973780, G5097463834, Biomedical Data Translator Technical Feasibility Assessment of Reasoning Tool: University of North Carolina at Chapel Hill, Drug Repurposing for Cancer Therapy: From Man to Molecules to Man, G9000071296
OpenAlex ID: W3112541288