Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug combinations
Jitobaom et al.
, Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug combinations
, BMC Pharmacology and Toxicology, doi:10.1186/s40360-022-00580-8 (date from earlier preprint) (In Vitro)
study showing a strong synergistic effect of combinations of ivermectin, niclosamide, and chloroquine, with >10x reduction in IC50
compared to individual drugs.15 In Vitro studies
support the efficacy of ivermectin [Boschi, Caly, Croci, De Forni, Delandre, Jeffreys, Jitobaom, Jitobaom (B), Li, Liu, Mody, Mountain Valley MD, Segatori, Surnar, Yesilbag]
Jitobaom et al., 18 Jun 2022, peer-reviewed, 8 authors.
email@example.com (corresponding author).
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: Jitobaom et al.
BMC Pharmacology and Toxicology
Synergistic anti‑SARS‑CoV‑2 activity
of repurposed anti‑parasitic drug combinations
Kunlakanya Jitobaom1, Chompunuch Boonarkart1, Suwimon Manopwisedjaroen2, Nuntaya Punyadee3,4,
Suparerk Borwornpinyo5, Arunee Thitithanyanont2, Panisadee Avirutnan3,4 and Prasert Auewarakul1*
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, niclosamideivermectin achieved the highest inhibitory level of over 99%. Combination synergy analysis showed niclosamideivermectin 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.
Keywords: SARS-CoV-2, Repurposed drug, Anti-parasitic drugs, Niclosamide, Ivermectin, Chloroquine
The spread of SARS-CoV-2 and the COVID-19 pandemic
has swept through countries and continents causing catastrophic loss of lives, public health, livelihood, and economy. Up to March 2021, more than hundred million cases
have been reported with over two million deaths . The
hope to get through the pandemic and resume normal
life relies heavily on vaccine deployment, which will still
take months or years in most less-developed countries
Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol
University, Bangkok 10700, Thailand
Full list of author information is available at the end of the article
. One of the reasons for the heavy loss of lives, hospital overload, and public panic is the lack of effective
treatment. Remdesivir is now the only antiviral drug with
emergency use authorization by US FDA . The drug is,
however, not yet widely available. Other FDA-approved
drugs are anti-inflammatory targeting host inflammatory responses . More drugs capable of inhibiting
SARS-CoV-2 replication are urgently needed not only for
treatment but also for reducing viral load and transmission . Many repurposed anti-parasitic drugs have been
shown to possess in vitro activity against SARS-CoV-2.
In vitro screenings of FDA-approved drugs have identified a number of anti-parasitic drugs with anti-SARSCoV-2 activity and potential..
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