Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug combinations
Issued Date
2022-12-01
Resource Type
eISSN
20506511
Scopus ID
2-s2.0-85132124100
Pubmed ID
35717393
Journal Title
BMC Pharmacology and Toxicology
Volume
23
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
BMC Pharmacology and Toxicology Vol.23 No.1 (2022)
Suggested Citation
Jitobaom K., Boonarkart C., Manopwisedjaroen S., Punyadee N., Borwornpinyo S., Thitithanyanont A., Avirutnan P., Auewarakul P. Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug combinations. BMC Pharmacology and Toxicology Vol.23 No.1 (2022). doi:10.1186/s40360-022-00580-8 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85299
Title
Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug combinations
Author's Affiliation
Other Contributor(s)
Abstract
Background: COVID-19 pandemic has claimed millions of lives and devastated the health service system, livelihood, and economy in many countries worldwide. Despite the vaccination programs in many countries, the spread of the pandemic continues, and effective treatment is still urgently needed. Although some antiviral drugs have been shown to be effective, they are not widely available. Repurposing of anti-parasitic drugs with in vitro anti-SARS-CoV-2 activity is a promising approach being tested in many clinical trials. Combination of these drugs is a plausible way to enhance their effectiveness. Methods: The in vitro anti-SARS-CoV-2 activity of combinations of niclosamide, ivermectin and chloroquine were evaluated in Vero E6 and lung epithelial cells, Calu-3. Results: All the two-drug combinations showed higher potency resulting in up to 4-fold reduction in the half maximal inhibitory concentration (IC50) values compared to individual drugs. Among these combinations, niclosamide-ivermectin achieved the highest inhibitory level of over 99%. Combination synergy analysis showed niclosamide-ivermectin combination to have the best synergy score with a mean Loewe synergy score of 4.28 and a peak synergy score of 24.6 in Vero E6 cells and a mean Loewe synergy score of 3.82 and a peak synergy score of 10.86 in Calu-3 cells. Conclusions: The present study demonstrated the benefit of drug combinations on anti-SARS-CoV-2 activity. Niclosamide and ivermectin showed the best synergistic profile and should be further tested in clinical trials.