Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug combinations

DOI record: { "DOI": "10.1186/s40360-022-00580-8", "ISSN": [ "2050-6511" ], "URL": "http://dx.doi.org/10.1186/s40360-022-00580-8", "abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>All the two-drug combinations showed higher potency resulting in up to 4-fold reduction in the half maximal inhibitory concentration (IC<jats:sub>50</jats:sub>) 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.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec>", "alternative-id": [ "580" ], "article-number": "41", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "5 January 2022" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "9 June 2022" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "18 June 2022" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Ethics approval and consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "Not applicable. This work does not involve the use of human subjects and animals. All the procedures do not require IRB approval." }, { "group": { "label": "Consent for publication", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "Not applicable. This work does not contain data from any individual person." }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 4, "value": "The authors declare that they have no competing interests." } ], "author": [ { "affiliation": [], "family": "Jitobaom", "given": "Kunlakanya", "sequence": "first" }, { "affiliation": [], "family": "Boonarkart", "given": "Chompunuch", "sequence": "additional" }, { "affiliation": [], "family": "Manopwisedjaroen", "given": "Suwimon", "sequence": "additional" }, { "affiliation": [], "family": "Punyadee", "given": "Nuntaya", "sequence": "additional" }, { "affiliation": [], "family": "Borwornpinyo", "given": "Suparerk", "sequence": "additional" }, { "affiliation": [], "family": "Thitithanyanont", "given": "Arunee", "sequence": "additional" }, { "affiliation": [], "family": "Avirutnan", "given": "Panisadee", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-4745-4291", "affiliation": [], "authenticated-orcid": false, "family": "Auewarakul", "given": "Prasert", "sequence": "additional" } ], "container-title": "BMC Pharmacology and Toxicology", "container-title-short": "BMC Pharmacol Toxicol", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2022, 6, 18 ] ], "date-time": "2022-06-18T09:02:54Z", "timestamp": 1655542974000 }, "deposited": { "date-parts": [ [ 2022, 6, 18 ] ], "date-time": "2022-06-18T09:12:48Z", "timestamp": 1655543568000 }, "funder": [ { "DOI": "10.13039/501100004192", "award": [ "P-20-52262" ], "doi-asserted-by": "publisher", "name": "National Science and Technology Development Agency" }, { "DOI": "10.13039/501100013238", "doi-asserted-by": "publisher", "name": "Faculty of Medicine Siriraj Hospital, Mahidol University" } ], "indexed": { "date-parts": [ [ 2022, 6, 18 ] ], "date-time": "2022-06-18T09:43:01Z", "timestamp": 1655545381613 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2022, 6, 18 ] ] }, "journal-issue": { "issue": "1", "published-print": { "date-parts": [ [ 2022, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 6, 18 ] ], "date-time": "2022-06-18T00:00:00Z", "timestamp": 1655510400000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 6, 18 ] ], "date-time": "2022-06-18T00:00:00Z", "timestamp": 1655510400000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1186/s40360-022-00580-8.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1186/s40360-022-00580-8/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1186/s40360-022-00580-8.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1186", "published": { "date-parts": [ [ 2022, 6, 18 ] ] }, "published-online": { "date-parts": [ [ 2022, 6, 18 ] ] }, "published-print": { "date-parts": [ [ 2022, 12 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1136/bmj.n1188", "author": "O Dyer", "doi-asserted-by": "publisher", "first-page": "n1188", "journal-title": "BMJ", "key": "580_CR1", "unstructured": "Dyer O. 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