Publication date: Aug 14, 2026
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. In this phase 2, double-blind, randomised, placebo-controlled trial, adults with mild-to-moderate COVID-19 within 3 days of symptom onset were randomly assigned (1:1:1) to receive placebo or inhaled SNS812 (100 mg or 200 mg) once daily for 7 days (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. 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 mg SNS812 group showed a shorter median time to SARS-CoV-2 antigen negativity (2. 9 vs 3. 6 days; p = 0. 007) and a faster viral load reduction rate (- 0. 755 vs - 0. 652; p = 0. 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 mg compared with placebo (median TTSR 6. 1 vs 8. 1 days; adjusted hazard ratio 2. 07, 95% CI 1. 30-3. 29; median TTSA 3. 6 vs 6. 5 days; adjusted hazard ratio 1. 81, 95% CI 1. 14-2. 88). 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.
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Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | COVID-19 |
| pathway | KEGG | RNA polymerase |
| disease | MESH | included |
| pathway | REACTOME | Reproduction |
| disease | MESH | severe acute respiratory syndrome |
| disease | MESH | XFG |
| disease | MESH | reinfection |
| drug | DRUGBANK | Ritonavir |
| pathway | KEGG | Viral replication |
| drug | DRUGBANK | Nicotine |
| drug | DRUGBANK | Oxygen |
| drug | DRUGBANK | Medical air |
| disease | MESH | overweight |
| disease | MESH | hypertension |
| disease | MESH | hepatitis |
| drug | DRUGBANK | Creatine |
| disease | MESH | chronic condition |
| disease | MESH | obesity |
| disease | MESH | chronic hepatitis |
| drug | DRUGBANK | Methionine |
| disease | MESH | fever |
| disease | MESH | cough |
| disease | MESH | aches |
| disease | MESH | chills |
| disease | MESH | runny nose |
| disease | MESH | headache |
| disease | MESH | nausea |
| disease | MESH | vomiting |
| disease | MESH | diarrhea |
| disease | MESH | smell loss |
| disease | MESH | Diabetes mellitus |
| disease | MESH | Asthma |
| pathway | KEGG | Asthma |
| disease | MESH | Thalassemia |