Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients

{ 'indexed': {'date-parts': [[2024, 8, 19]], 'date-time': '2024-08-19T04:28:08Z', 'timestamp': 1724041688354}, 'reference-count': 49, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2021, 12, 6]], 'date-time': '2021-12-06T00:00:00Z', 'timestamp': 1638748800000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2021, 12, 6]], 'date-time': '2021-12-06T00:00:00Z', 'timestamp': 1638748800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:p>Azvudine (FNC) is a nucleoside analog that inhibits ' 'HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against ' 'SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate ' 'analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC<jats:sub>50</jats:sub> ' 'between 1.2 and 4.3\u2009μM, depending on viruses or cells, and selective index (SI) in 15–83 ' 'range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with ' 'FNC triphosphate (the active form) concentrated in the thymus and peripheral blood ' 'mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07\u2009' 'mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, ' 'alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. ' 'Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, ' 'single-arm clinical trial of FNC on compassionate use (<jats:italic>n</jats:italic>\u2009' '=\u200931) showed that oral FNC (5\u2009mg, qd) cured all COVID-19 patients, with 100% viral ' 'ribonucleic acid negative conversion in 3.29\u2009±\u20092.22 days (range: 1–9 days) and 100% ' 'hospital discharge rate in 9.00\u2009±\u20094.93 days (range: 2–25 days). The side-effect of ' 'FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might ' 'cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by ' 'promoted immunity.</jats:p>', 'DOI': '10.1038/s41392-021-00835-6', 'type': 'journal-article', 'created': {'date-parts': [[2021, 12, 6]], 'date-time': '2021-12-06T08:02:47Z', 'timestamp': 1638777767000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 112, 'title': 'Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients', 'prefix': '10.1038', 'volume': '6', 'author': [ {'given': 'Jin-Lan', 'family': 'Zhang', 'sequence': 'first', 'affiliation': []}, {'given': 'Yu-Huan', 'family': 'Li', 'sequence': 'additional', 'affiliation': []}, {'given': 'Lu-Lu', 'family': 'Wang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hong-Qi', 'family': 'Liu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Shuai-Yao', 'family': 'Lu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yong', 'family': 'Liu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ke', 'family': 'Li', 'sequence': 'additional', 'affiliation': []}, {'given': 'Bin', 'family': 'Liu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Su-Yun', 'family': 'Li', 'sequence': 'additional', 'affiliation': []}, {'given': 'Feng-Min', 'family': 'Shao', 'sequence': 'additional', 'affiliation': []}, {'given': 'Kun', 'family': 'Wang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ning', 'family': 'Sheng', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rui', 'family': 'Li', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jin-Jin', 'family': 'Cui', 'sequence': 'additional', 'affiliation': []}, {'given': 'Pei-Chun', 'family': 'Sun', 'sequence': 'additional', 'affiliation': []}, {'given': 'Chun-Xia', 'family': 'Ma', 'sequence': 'additional', 'affiliation': []}, {'given': 'Bo', 'family': 'Zhu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Zhe', 'family': 'Wang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yuan-Hao', 'family': 'Wan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Shi-Shan', 'family': 'Yu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yongsheng', 'family': 'Che', 'sequence': 'additional', 'affiliation': []}, {'given': 'Chao-Yang', 'family': 'Wang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Chen', 'family': 'Wang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Qiangqian', 'family': 'Zhang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Li-Min', 'family': 'Zhao', 'sequence': 'additional', 'affiliation': []}, {'given': 'Xiao-Zhong', 'family': 'Peng', 'sequence': 'additional', 'affiliation': []}, {'given': 'Zhenshun', 'family': 'Cheng', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jun-Biao', 'family': 'Chang', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-1173-685X', 'authenticated-orcid': False, 'given': 'Jian-Dong', 'family': 'Jiang', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2021, 12, 6]]}, 'reference': [ { 'key': '835_CR1', 'doi-asserted-by': 'publisher', 'first-page': '418', 'DOI': '10.1002/jmv.25681', 'volume': '92', 'author': 'Y Chen', 'year': '2020', 'unstructured': 'Chen, Y., Liu, Q. & Guo, D. 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