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Ltd"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biomed Sci"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>SARS-CoV-2 remains a global health threat because ongoing viral evolution and immune evasion reduce the effectiveness of existing therapies. SNS812 is an inhaled small interfering RNA targeting a highly conserved region of the viral RNA-dependent RNA polymerase gene, representing a strategy that may enable broader antiviral activity against emerging variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this phase 2, double-blind, randomised, placebo-controlled trial, adults with mild-to-moderate COVID-19 within 3\u00a0days of symptom onset were randomly assigned (1:1:1) to receive placebo or inhaled SNS812 (100\u00a0mg or 200\u00a0mg) once daily for 7\u00a0days (ClinicalTrials.gov identifier: NCT05941793). Safety was the primary endpoint. Secondary endpoints included the time to sustained alleviation (TTSA) and resolution (TTSR) for prespecified composite target symptoms and individual symptoms. Virological outcomes were exploratory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 135 participants were enrolled, with more than 90% infected with immune-evasive SARS-CoV-2 variants. No treatment-related adverse events or serious adverse events were reported. In exploratory analyses, the 200\u00a0mg SNS812 group showed a shorter median time to SARS-CoV-2 antigen negativity (2.9 vs 3.6\u00a0days; p\u2009=\u20090.007) and a faster viral load reduction rate (\u2212\u20090.755 vs\u2009\u2212\u20090.652; p\u2009=\u20090.040), demonstrating dose-dependent virological effects. In the modified intention-to-treat population, exploratory symptom analyses showed shorter TTSA and TTSR for prespecified target symptoms with SNS812 200\u00a0mg compared with placebo (median TTSR 6.1 vs 8.1\u00a0days; adjusted hazard ratio 2.07, 95% CI 1.30\u20133.29; median TTSA 3.6 vs 6.5\u00a0days; adjusted hazard ratio 1.81, 95% CI 1.14\u20132.88).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inhaled SNS812 was safe and well tolerated and showed dose-dependent antiviral activity, with exploratory signals of symptomatic improvement in adults with mild-to-moderate COVID-19 infected with immune-evasive variants. These findings support further evaluation in larger, adequately powered trials, including older and higher-risk populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12929-026-01284-5","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:51:38Z","timestamp":1786686698000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and antiviral activity of inhaled siRNA SNS812 for treatment of mild-to-moderate COVID-19: a phase 2 randomized trial"],"prefix":"10.1186","volume":"33","author":[{"given":"Shey-Ying","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sui-Yuan","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chung","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Che","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Yuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jer-Hwa","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Pin","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Hao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhong-Lin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pai-Chien","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsong-Yih","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Wang","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Yi","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ju","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen-Fu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang-Yun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-6048","authenticated-orcid":false,"given":"Pan-Chyr","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"1284_CR1","doi-asserted-by":"publisher","first-page":"e82","DOI":"10.1016\/S1473-3099(23)00813-7","volume":"24","author":"Y Kaku","year":"2024","unstructured":"Kaku Y, Okumura K, Padilla-Blanco M, et al. 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