Sofosbuvir/Ledipasvir in Combination or Nitazoxanide Alone are Safe and Efficient Treatments for COVID-19 Infection: A Randomized Controlled Trial for Repurposing antivirals

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Global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments 2020." }, { "DOI": "10.1186/s13063-020-04988-7", "article-title": "The efficacy and safety of Ivermectin in patients with mild and moderate COVID-19: A structured summary of a study protocol for a randomized controlled trial", "author": "Hosseini", "doi-asserted-by": "crossref", "issue": "1", "journal-title": "Trials", "key": "10.1016/j.ajg.2022.04.005_b0020", "volume": "22", "year": "2021" }, { "DOI": "10.1001/jama.2020.0757", "article-title": "Coronavirus infections—more than just the common cold", "author": "Paules", "doi-asserted-by": "crossref", "first-page": "707", "issue": "8", "journal-title": "Jama", "key": "10.1016/j.ajg.2022.04.005_b0025", "volume": "323", "year": "2020" }, { "DOI": "10.1038/s41467-019-10280-3", "article-title": "Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors", "author": "Kirchdoerfer", "doi-asserted-by": "crossref", "first-page": "1", "journal-title": "Nature communications", "key": "10.1016/j.ajg.2022.04.005_b0030", "volume": "10", "year": "2019" }, { "DOI": "10.2183/pjab.93.027", "article-title": "Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase", "author": "FURUTA", "doi-asserted-by": "crossref", "first-page": "449", "issue": "7", "journal-title": "Proceedings of the Japan Academy, Series B", "key": "10.1016/j.ajg.2022.04.005_b0035", "volume": "93", "year": "2017" }, { "DOI": "10.1038/nature17180", "article-title": "Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys", "author": "Warren", "doi-asserted-by": "crossref", "first-page": "381", "issue": "7594", "journal-title": "Nature", "key": "10.1016/j.ajg.2022.04.005_b0040", "volume": "531", "year": "2016" }, { "DOI": "10.1101/2020.01.30.927574", "doi-asserted-by": "crossref", "key": "10.1016/j.ajg.2022.04.005_b0045", "unstructured": "Ju J, Kumar S, Li X, Jockusch S, Russo JJ. Nucleotide Analogues as Inhibitors of Viral Polymerases. bioRxiv 2020:2020.2001.2030.927574." }, { "DOI": "10.12688/f1000research.22457.1", "doi-asserted-by": "crossref", "key": "10.1016/j.ajg.2022.04.005_b0050", "unstructured": "Chen Y, Yiu C, Wong K. Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CLpro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates [version 1; peer review: 3 approved]. 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Journal of Antimicrobial Chemotherapy 2020;75:3379-3385." }, { "DOI": "10.1016/j.antiviral.2014.07.014", "article-title": "Nitazoxanide: a first-in-class broad-spectrum antiviral agent", "author": "Rossignol", "doi-asserted-by": "crossref", "first-page": "94", "journal-title": "Antiviral research", "key": "10.1016/j.ajg.2022.04.005_b0150", "volume": "110", "year": "2014" }, { "DOI": "10.1371/journal.ppat.1002691", "article-title": "Nitazoxanide stimulates autophagy and inhibits mTORC1 signaling and intracellular proliferation of Mycobacterium tuberculosis", "author": "Lam", "doi-asserted-by": "crossref", "first-page": "e1002691", "issue": "5", "journal-title": "PLoS pathogens", "key": "10.1016/j.ajg.2022.04.005_b0155", "volume": "8", "year": "2012" }, { "article-title": "Early use of nitazoxanide in mild Covid-19 disease: randomised, placebo-controlled trial", "author": "Rocco", "journal-title": "European Respiratory Journal", "key": "10.1016/j.ajg.2022.04.005_b0160", "year": "2020" }, { "DOI": "10.1002/jmv.26880", "article-title": "Effect of a combination of nitazoxanide, ribavirin, and ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-19", "author": "Elalfy", "doi-asserted-by": "crossref", "first-page": "3176", "issue": "5", "journal-title": "Journal of medical virology", "key": "10.1016/j.ajg.2022.04.005_b0165", "volume": "93", "year": "2021" }, { "DOI": "10.1016/j.medj.2020.04.001", "article-title": "Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial", "author": "Li", "doi-asserted-by": "crossref", "first-page": "105", "issue": "1", "journal-title": "Med", "key": "10.1016/j.ajg.2022.04.005_b0170", "volume": "1", "year": "2020" }, { "DOI": "10.1056/NEJMoa2001282", "article-title": "A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19", "author": "Cao", "doi-asserted-by": "crossref", "journal-title": "New England Journal of Medicine", "key": "10.1016/j.ajg.2022.04.005_b0175", "year": "2020" }, { "DOI": "10.1186/s12985-020-01412-z", "article-title": "Favipiravir versus other antiviral or standard of care for COVID-19 treatment: a rapid systematic review and meta-analysis", "author": "Shrestha", "doi-asserted-by": "crossref", "first-page": "141", "journal-title": "Virology Journal", "key": "10.1016/j.ajg.2022.04.005_b0180", "volume": "17", "year": "2020" }, { "DOI": "10.1093/cid/ciaa1176", "doi-asserted-by": "crossref", "key": "10.1016/j.ajg.2022.04.005_b0185", "unstructured": "Ivashchenko AA, Dmitriev KA, Vostokova NV, Azarova VN, Blinow AA, Egorova AN, et al. 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