Efficacy and safety evaluation of Azvudine in the prospective treatment of COVID-19 based on four phase III clinical trials

{ 'DOI': '10.3389/fphar.2023.1228548', 'ISSN': ['1663-9812'], 'URL': 'http://dx.doi.org/10.3389/fphar.2023.1228548', 'abstract': '<jats:p>Azvudine (FNC) is a synthetic nucleoside analog used to treat adult patients living ' 'with human immunodeficiency virus-1 (HIV-1) infection with high viral load. After ' 'phosphorylation, Azvudine inhibits RNA-dependent RNA polymerase, leading to the ' 'discontinuation of RNA chain synthesis in viruses. In addition, Azvudine is the first ' 'dual-target nucleoside oral drug worldwide to simultaneously target reverse transcriptase and ' 'viral infectivity factors in the treatment of HIV infection. On 9 August 2022, Azvudine was ' 'incorporated into the Guidelines for the Diagnosis and Treatment of Coronavirus Disease 2019 ' '(version ninth) issued by the National Health Commission and the National Administration of ' 'Traditional Chinese Medicine. The recommended oral dose of Azvudine for the treatment of ' 'moderate coronavirus disease 2019 (COVID-19) is 5\xa0mg once daily, and the duration of ' 'Azvudine treatment should not exceed 14\xa0days. Four phase III clinical trials were ' 'performed during 2020–2022 to evaluate the efficacy and safety of Azvudine in the treatment ' 'of COVID-19. The results revealed that Azvudine could reduce nucleic acid-negative conversion ' 'time, viral load, and time to improvement in clinical conditions in patients with moderate ' 'COVID-19. In addition, Azvudine exhibited good safety and tolerance. Thereafter, Azvudine was ' 'incorporated into the Chinese guidelines and expert consensus for the treatment of COVID-19 ' 'and was highly approbated. Furthermore, Azvudine was also included in the Chinese guidelines ' 'for HIV infection.</jats:p>', 'alternative-id': ['10.3389/fphar.2023.1228548'], 'author': [{'affiliation': [], 'family': 'Zhu', 'given': 'Ke-Wei', 'sequence': 'first'}], 'container-title': 'Frontiers in Pharmacology', 'container-title-short': 'Front. Pharmacol.', 'content-domain': {'crossmark-restriction': True, 'domain': ['frontiersin.org']}, 'created': {'date-parts': [[2023, 8, 25]], 'date-time': '2023-08-25T05:14:10Z', 'timestamp': 1692940450000}, 'deposited': { 'date-parts': [[2023, 8, 25]], 'date-time': '2023-08-25T05:14:32Z', 'timestamp': 1692940472000}, 'indexed': {'date-parts': [[2023, 8, 26]], 'date-time': '2023-08-26T08:42:18Z', 'timestamp': 1693039338690}, 'is-referenced-by-count': 0, 'issued': {'date-parts': [[2023, 8, 24]]}, 'license': [ { 'URL': 'https://creativecommons.org/licenses/by/4.0/', 'content-version': 'vor', 'delay-in-days': 0, 'start': { 'date-parts': [[2023, 8, 24]], 'date-time': '2023-08-24T00:00:00Z', 'timestamp': 1692835200000}}], 'link': [ { 'URL': 'https://www.frontiersin.org/articles/10.3389/fphar.2023.1228548/full', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'member': '1965', 'original-title': [], 'prefix': '10.3389', 'published': {'date-parts': [[2023, 8, 24]]}, 'published-online': {'date-parts': [[2023, 8, 24]]}, 'publisher': 'Frontiers Media SA', 'reference': [ { 'DOI': '10.12290/xhyxzz.2022-0097', 'article-title': 'Chinese guidelines for diagnosis and treatment of human ' 'immunodeficiency virus infection/acquired immunodeficiency syndrome ' '(2021 edition)', 'doi-asserted-by': 'publisher', 'first-page': '203', 'journal-title': 'Med. J. Peking Union Med. Coll. Hosp. [CNKI]', 'key': 'B1', 'volume': '13', 'year': '2021'}, { 'DOI': '10.1136/bmj.n436', 'article-title': 'Severe covid-19 pneumonia: pathogenesis and clinical management', 'author': 'Attaway', 'doi-asserted-by': 'publisher', 'first-page': 'n436', 'journal-title': 'BMJ', 'key': 'B2', 'volume': '372', 'year': '2021'}, { 'author': 'Cabral', 'key': 'B3', 'volume-title': 'Serial viral load analysis by ddpcr to evaluate fnc efficacy and safety ' 'in the treatment of moderate cases of covid-19, 21 november 2022, ' 'PREPRINT', 'year': ''}, { 'DOI': '10.1056/NEJMoa2208822', 'article-title': 'VV116 versus nirmatrelvir-ritonavir for oral treatment of covid-19', 'author': 'Cao', 'doi-asserted-by': 'publisher', 'first-page': '406', 'journal-title': 'N. Engl. J. Med.', 'key': 'B4', 'volume': '388', 'year': '2023'}, { 'key': 'B5', 'volume-title': 'The 17th national congress of Chinese society of infectious diseases and ' 'the 3rd international forum on infectious diseases and clinical ' 'microbiology', 'year': '2022'}, { 'author': 'ClinicalTrials', 'key': 'B6', 'volume-title': 'Clinical data and adverse reactions of the oral drug Azvudine for ' 'COVID-19', 'year': '2022'}, { 'DOI': '10.3389/fmed.2023.1143485', 'article-title': 'Serial viral load analysis by DDPCR to evaluate FNC efficacy and safety ' 'in the treatment of mild cases of COVID-19', 'author': 'da Silva', 'doi-asserted-by': 'publisher', 'first-page': '1143485', 'journal-title': 'Front. Med. (Lausanne)', 'key': 'B7', 'volume': '10', 'year': '2023'}, { 'DOI': '10.1021/acsomega.2c03881', 'article-title': 'Novel investigational anti-SARS-CoV-2 agent ensitrelvir "S-217622": a ' 'very promising potential universal broad-spectrum antiviral at the ' 'therapeutic frontline of coronavirus species', 'author': 'Eltayb', 'doi-asserted-by': 'publisher', 'first-page': '5234', 'journal-title': 'ACS Omega', 'key': 'B8', 'volume': '8', 'year': '2023'}, { 'DOI': '10.1183/16000617.0138-2021', 'article-title': 'COVID-19 pneumonia: pathophysiology and management', 'author': 'Gattinoni', 'doi-asserted-by': 'publisher', 'first-page': '210138', 'journal-title': 'Eur. Respir. Rev.', 'key': 'B9', 'volume': '30', 'year': '2021'}, { 'DOI': '10.3760/j.issn.1673-4777.2023.02.001', 'article-title': 'Guidelines for the Diagnosis and Treatment of Coronavirus Disease 2019 ' '(trial version tenth)', 'doi-asserted-by': 'publisher', 'first-page': '161', 'journal-title': 'China Med. [CNKI]', 'key': 'B10', 'volume': '18', 'year': '2023'}, { 'key': 'B16', 'volume-title': 'Genuine Biotech raises $100 million in series B financing, accelerating ' "commercialization of world's first dual-target anti-HIV drug", 'year': '2021'}, { 'key': 'B13', 'volume-title': "Genuine Biotech and Fosun pharma donated 100 million yuan's worth of " 'oral drug for COVID-19, azvudine, to rural areas', 'year': ''}, { 'key': 'B14', 'volume-title': 'Genuine Biotech and Fosun pharma donated nearly 300,000 bottles of ' "azvudine tablets to China's rural areas", 'year': ''}, { 'key': 'B11', 'volume-title': 'Good news! Genuine Biotech won the 2022 annual award of henan socially ' 'responsible Enterprise', 'year': ''}, { 'key': 'B12', 'volume-title': 'Good news, azvudine tablets is officially included in the national ' 'reimbursement drug list', 'year': ''}, { 'DOI': '10.1056/NEJMoa2118542', 'article-title': 'Oral nirmatrelvir for high-risk, nonhospitalized adults with covid-19', 'author': 'Hammond', 'doi-asserted-by': 'publisher', 'first-page': '1397', 'journal-title': 'N. Engl. J. Med.', 'key': 'B15', 'volume': '386', 'year': '2022'}, {'key': 'B17', 'volume-title': 'Package insert of Azifudine tablets', 'year': '2022'}, { 'DOI': '10.1056/NEJMoa2116044', 'article-title': 'Molnupiravir for oral treatment of covid-19 in nonhospitalized patients', 'author': 'Jayk Bernal', 'doi-asserted-by': 'publisher', 'first-page': '509', 'journal-title': 'N. Engl. J. Med.', 'key': 'B18', 'volume': '386', 'year': '2022'}, { 'DOI': '10.1038/s41580-021-00432-z', 'article-title': 'Structures and functions of coronavirus replication-transcription ' 'complexes and their relevance for SARS-CoV-2 drug design', 'author': 'Malone', 'doi-asserted-by': 'publisher', 'first-page': '21', 'journal-title': 'Nat. Rev. Mol. Cell. Biol.', 'key': 'B19', 'volume': '23', 'year': '2022'}, { 'DOI': '10.16505/j.2095-0136.2022.0023', 'article-title': 'Guidelines for the diagnosis and treatment of coronavirus disease 2019 ' '(trial version ninth)', 'doi-asserted-by': 'publisher', 'first-page': '161', 'journal-title': 'Chin. J. Viral Dis. [CNKI]', 'key': 'B20', 'volume': '12', 'year': '2022'}, { 'key': 'B21', 'volume-title': 'Azvudine was conditionally approved by the national medical products ' 'administration', 'year': '2021'}, { 'key': 'B22', 'volume-title': 'The application that coronavirus disease 2019 (COVID-19) was added into ' 'the indications of Azvudine was conditionally approved by the National ' 'Medical Products Administration', 'year': '2022'}, { 'DOI': '10.3390/v14050961', 'article-title': 'Antiviral drug discovery for the treatment of COVID-19 infections', 'author': 'Ng', 'doi-asserted-by': 'publisher', 'first-page': '961', 'journal-title': 'Viruses', 'key': 'B23', 'volume': '14', 'year': '2022'}, { 'article-title': 'The national health commission includes azvudine into the guidelines ' 'for the diagnosis and treatment of coronavirus disease 2019 (version ' 'ninth)', 'first-page': '283', 'journal-title': 'Chin. J. Viral Dis. [CNKI]', 'key': 'B24', 'volume': '12', 'year': '2022'}, { 'DOI': '10.1007/s00044-022-02970-3', 'article-title': 'Evaluation of a series of nucleoside analogs as effective ' 'anticoronaviral-2 drugs against the Omicron-B.1.1.529/BA.2 subvariant: ' 'a repurposing research study', 'author': 'Rabie', 'doi-asserted-by': 'publisher', 'first-page': '326', 'journal-title': 'Med. Chem. Res.', 'key': 'B25', 'volume': '32', 'year': '2023'}, { 'DOI': '10.1021/acsbiomedchemau.2c00039', 'article-title': 'Forodesine and riboprine exhibit strong anti-SARS-CoV-2 repurposing ' 'potential: in silico and in vitro studies', 'author': 'Rabie', 'doi-asserted-by': 'publisher', 'first-page': '565', 'journal-title': 'ACS Bio Med Chem Au', 'key': 'B26', 'volume': '2', 'year': '2022'}, { 'DOI': '10.1021/acsomega.2c08073', 'article-title': 'Promising experimental anti-SARS-CoV-2 agent “SLL-0197800”: the ' 'prospective universal inhibitory properties against the coming versions ' 'of the coronavirus', 'author': 'Rabie', 'doi-asserted-by': 'publisher', 'journal-title': 'ACS Omega', 'key': 'B27', 'volume': '8', 'year': '2023'}, { 'DOI': '10.1021/acsomega.1c07095', 'article-title': 'Efficacious preclinical repurposing of the nucleoside analogue ' 'didanosine against COVID-19 polymerase and exonuclease', 'author': 'Rabie', 'doi-asserted-by': 'publisher', 'first-page': '21385', 'journal-title': 'ACS Omega', 'key': 'B28', 'volume': '7', 'year': ''}, { 'DOI': '10.1007/s12033-022-00551-8', 'article-title': 'Potent dual polymerase/exonuclease inhibitory activities of antioxidant ' 'aminothiadiazoles against the COVID-19 Omicron virus: a promising in ' 'silico/in vitro repositioning research study', 'author': 'Rabie', 'doi-asserted-by': 'publisher', 'first-page': '1', 'journal-title': 'Mol. Biotechnol.', 'key': 'B29', 'year': '2023'}, { 'DOI': '10.1021/acsomega.1c05998', 'article-title': 'Potent inhibitory activities of the adenosine analogue cordycepin on ' 'SARS-CoV-2 replication', 'author': 'Rabie', 'doi-asserted-by': 'publisher', 'first-page': '2960', 'journal-title': 'ACS Omega', 'key': 'B30', 'volume': '7', 'year': ''}, { 'DOI': '10.1016/j.cbi.2021.109480', 'article-title': 'Potent toxic effects of Taroxaz-104 on the replication of SARS-CoV-2 ' 'particles', 'author': 'Rabie', 'doi-asserted-by': 'publisher', 'first-page': '109480', 'journal-title': 'Chem. Biol. Interact.', 'key': 'B31', 'volume': '343', 'year': ''}, { 'DOI': '10.1016/j.crphar.2021.100055', 'article-title': 'Teriflunomide: a possible effective drug for the comprehensive ' 'treatment of COVID-19', 'author': 'Rabie', 'doi-asserted-by': 'publisher', 'first-page': '100055', 'journal-title': 'Curr. Res. Pharmacol. Drug Discov.', 'key': 'B32', 'volume': '2', 'year': ''}, { 'DOI': '10.1039/d0nj03708g', 'article-title': 'Two antioxidant 2,5-disubstituted-1,3,4-oxadiazoles (CoViTris2020 and ' 'ChloViD2020): successful repurposing against COVID-19 as the first ' 'potent multitarget anti-SARS-CoV-2 drugs', 'author': 'Rabie', 'doi-asserted-by': 'publisher', 'first-page': '761', 'journal-title': 'New J. Chem.', 'key': 'B33', 'volume': '45', 'year': ''}, { 'DOI': '10.1002/advs.202001435', 'article-title': 'A randomized, open-label, controlled clinical trial of azvudine tablets ' 'in the treatment of mild and Common COVID-19, a pilot study', 'author': 'Ren', 'doi-asserted-by': 'publisher', 'first-page': 'e2001435', 'journal-title': 'Adv. Sci. (Weinh)', 'key': 'B34', 'volume': '7', 'year': '2020'}, { 'DOI': '10.1016/j.ejmech.2021.113201', 'article-title': 'RNA-dependent RNA polymerase (RdRp) inhibitors: the current landscape ' 'and repurposing for the COVID-19 pandemic', 'author': 'Tian', 'doi-asserted-by': 'publisher', 'first-page': '113201', 'journal-title': 'Eur. J. Med. Chem.', 'key': 'B35', 'volume': '213', 'year': '2021'}, { 'DOI': '10.1038/s41579-020-00468-6', 'article-title': 'Coronavirus biology and replication: implications for SARS-CoV-2', 'author': "V'Kovski", 'doi-asserted-by': 'publisher', 'first-page': '155', 'journal-title': 'Nat. Rev. Microbiol.', 'key': 'B36', 'volume': '19', 'year': '2021'}, { 'DOI': '10.1080/13543776.2021.1880568', 'article-title': 'SARS-CoV-2 RNA-dependent RNA polymerase as a therapeutic target for ' 'COVID-19', 'author': 'Vicenti', 'doi-asserted-by': 'publisher', 'first-page': '325', 'journal-title': 'Expert Opin. Ther. Pat.', 'key': 'B37', 'volume': '31', 'year': '2021'}, { 'author': 'Xinhua', 'key': 'B38', 'volume-title': 'China focus: COVID-19 response further optimized with 10 new measures', 'year': ''}, { 'key': 'B39', 'volume-title': "China grants conditional approval for Pfizer's oral COVID-19 drug", 'year': ''}, { 'DOI': '10.1038/s41579-021-00630-8', 'article-title': 'Structural biology of SARS-CoV-2 and implications for therapeutic ' 'development', 'author': 'Yang', 'doi-asserted-by': 'publisher', 'first-page': '685', 'journal-title': 'Nat. Rev. Microbiol.', 'key': 'B40', 'volume': '19', 'year': '2021'}, { 'DOI': '10.1038/s41392-020-00351-z', 'article-title': 'Azvudine (FNC): a promising clinical candidate for COVID-19 treatment', 'author': 'Yu', 'doi-asserted-by': 'publisher', 'first-page': '236', 'journal-title': 'Signal Transduct. Target Ther.', 'key': 'B41', 'volume': '5', 'year': '2020'}, { 'article-title': 'Clinical study of Azfudine against COVID-19', 'author': 'Zhang', 'key': 'B42', 'volume-title': 'The 17th national congress of Chinese society of infectious diseases and ' 'the 3rd international forum on infectious diseases and clinical ' 'microbiology', 'year': '2022'}, { 'DOI': '10.3760/cma.j.issn.1674-2397.2023.01.003', 'article-title': 'Interpretation of Expert Consensus on Antiviral Therapy of COVID-19', 'author': 'Zhang', 'doi-asserted-by': 'publisher', 'first-page': '21', 'journal-title': 'Chin. J. Clin. Infect. Dis.', 'key': 'B43', 'volume': '16', 'year': '2023'}, { 'DOI': '10.1038/s41392-021-00835-6', 'article-title': 'Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating ' 'COVID-19 patients', 'author': 'Zhang', 'doi-asserted-by': 'publisher', 'first-page': '414', 'journal-title': 'Signal Transduct. Target Ther.', 'key': 'B44', 'volume': '6', 'year': '2021'}, { 'DOI': '10.1080/21645515.2023.2229704', 'article-title': 'Why is it necessary to improve COVID-19 vaccination coverage in older ' 'people? How to improve the vaccination coverage?', 'author': 'Zhu', 'doi-asserted-by': 'publisher', 'first-page': '2229704', 'journal-title': 'Hum. Vaccin Immunother.', 'key': 'B45', 'volume': '19', 'year': '2023'}, { 'DOI': '10.1021/acsptsci.3c00134', 'article-title': 'Deuremidevir and Simnotrelvir–Ritonavir for the Treatment of COVID-19', 'author': 'Zhu', 'doi-asserted-by': 'publisher', 'journal-title': 'ACS Pharmacol. Transl. Sci', 'key': 'B46', 'year': ''}], 'reference-count': 46, 'references-count': 46, 'relation': {}, 'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fphar.2023.1228548/full'}}, 'score': 1, 'short-title': [], 'source': 'Crossref', 'subject': ['Pharmacology (medical)', 'Pharmacology'], 'subtitle': [], 'title': 'Efficacy and safety evaluation of Azvudine in the prospective treatment of COVID-19 based on ' 'four phase III clinical trials', 'type': 'journal-article', 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'volume': '14'}