Xiannuoxin for COVID-19: real-time analysis of 8 studies

Xiannuoxin is a combination of simnotrelvir and ritonavir. Simnotrelvir is a first generation SARS-CoV-2 3CL protease inhibitor1. Ritonavir is a HIV drug used to boost the levels of simnotrelvir in the body by inhibiting its metabolism. Xiannuoxin was adopted in 1 country.


Dec 1	Covid Analysis	Xiannuoxin for COVID-19: real-time meta analysis of 2 studies
	Meta analysis using the most serious outcome reported shows 38% [-46‑73%] lower risk, without reaching statistical significance. Currently all studies are RCTs. One study shows significant benefit. Studies to date are from only..
Jul 1	Li et al., BMC Infectious Diseases, doi:10.1186/s12879-025-11195-9	Real-world effectiveness of simnotrelvir-ritonavir versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the omicron wave in China: a retrospective cohort study
	Retrospective 585 hospitalized COVID-19 patients in China showing that xiannuoxin provided better clinical improvement than paxlovid. There were no significant differences for progression, mortality, or respiratory support.
Apr 2	Zhao et al., Antimicrobial Agents and Chemotherapy, doi:10.1128/aac.01556-24	Potent antiviral activity of simnotrelvir against key epidemic SARS-CoV-2 variants with a high resistance barrier
	In vitro and clinical study showing potent antiviral activity of simnotrelvir against SARS-CoV-2 variants with a high resistance barrier. Authors demonstrated simnotrelvir's efficacy against multiple Omicron variants including BA.1, BA.4,..
Jan 15 2024	Jung et al., Toxics, doi:10.3390/toxics12010073	Ritonavir Has Reproductive Toxicity Depending on Disrupting PI3K/PDK1/AKT Signaling Pathway
	In vitro study on boar spermatozoa showing that the HIV drug ritonavir (part of paxlovid and xiannuoxin) causes reproductive toxicity by disrupting the PI3K/PDK1/AKT signaling pathway. Ritonavir suppressed sperm functions including motili..
Dec 31 2023	Yang et al., European Journal of Pharmaceutical Sciences, doi:10.1016/j.ejps.2023.106598	A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects
	RCT 72 healthy subjects evaluating safety, tolerability, and pharmacokinetics of simnotrelvir (SSD8432, SIM0417), a 3CL protease inhibitor, alone or co-administered with ritonavir at various single and multiple ascending oral doses and un..
Dec 31 2023	Bischof, E., Aging and disease, doi:10.14336/AD.2023.0318	Mitigating COVID-19 Mortality and Morbidity in China's Aging Population: A Focus on Available Medications and Future Developments
	Review focusing on 3CL protease inhibitors. First generation inhibitors like paxlovid and simnotrelvir require boosting with ritonavir, which can cause drug-drug interactions and other issues. Second generation inhibitors like ensitrelvir..
Oct 13 2023	Jiang et al., Nature Communications, doi:10.1038/s41467-023-42102-y	Structure-based development and preclinical evaluation of the SARS-CoV-2 3C-like protease inhibitor simnotrelvir
	In vitro and mouse study showing the development and preclinical evaluation of the SARS-CoV-2 3C-like protease (3CL^pro) inhibitor simnotrelvir (SSD8432, SIM0417, part of xiannuoxin) as an orally bioavailable COVID-19 therapeutic agent...
Sep 30 2023	Wang et al., The Lancet Regional Health - Western Pacific, doi:10.1016/j.lanwpc.2023.100835	Efficacy and safety of SIM0417 (SSD8432) plus ritonavir for COVID-19 treatment: a randomised, double-blind, placebo-controlled, phase 1b trial
	68% faster recovery (p=0.06) and 38% improved viral clearance (p=0.11). RCT 32 adults with asymptomatic, mild or moderate COVID-19 in China showing greater viral load reduction and faster time to symptom alleviation with xuannuoxin (simnotrelvir plus ritonavir) compared to placebo. All adverse events were mild.
Jul 31 2023	Lu et al., Progress in Pharmaceutical Sciences, doi:10.20053/j.issn1001-5094.2023.07.002	XIANNUOXIN®: China’s First Anti-SARS-CoV-2 Drug Targeting 3C-like Protease
	Review of the development and approval of Xiannuoxin, the first domestic anti-COVID-19 drug targeting the 3C-like protease (3CL^pro) approved in China. Xiannuoxin was jointly developed by Simcere Pharmaceutical Group, Shanghai Institute of..
Jan 29 2023	Cao et al., New England Journal of Medicine, doi:10.1056/NEJMoa2301425 (press release 1/29/2023)	Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19
	17% faster recovery (p=0.003). RCT 1,208 outpatients with mild-moderate COVID-19 in China, showing faster symptom resolution (by 35.8 hours) and faster viral clearance with xiannuoxin (simnotrelvir plus ritonavir) twice daily for 5 days.

References

Bischof, E., Mitigating COVID-19 Mortality and Morbidity in China's Aging Population: A Focus on Available Medications and Future Developments, Aging and disease, doi:10.14336/AD.2023.0318.aginganddisease.org, doi.org.