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leritrelvir (RAY1216 / Le Ruiling / leritrelvir)

✓ Approved

Guangdong Raynovent Biotech Co., Ltd · · Small Molecule

What is leritrelvir?

leritrelvir is a small molecule developed by Guangdong Raynovent Biotech Co., Ltd. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesRAY1216, Le Ruiling, leritrelvir
CompanyGuangdong Raynovent Biotech Co., Ltd
Drug ClassSmall Molecule
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Guangdong Raynovent Biotech Co., Ltd

Mechanism of Action

Molecular Targets

leritrelvir acts on 1 molecular target:

(ORF1ab)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

leritrelvir is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Infections and infestationsCOVID-19✓ Approved

Related Research Articles

PubMedEuropean journal of medicinal chemistry2026-06-28

Exploring chemical space based on Transformation to design broad-spectrum 3CLpro inhibitors against coronavirus.

Gu Zhihao Z, Qi Zhenkai Z, Chen Zhenfei Z, Li Jiao J et al.

How to efficiently explore chemical space to discover new compounds remains an important challenge in drug discovery. In this work, we introduce a Transformation strategy that enables efficient, scaffold-guided exploration of sub-chemical space around known bioactive molecules to obtain broad-spectrum inhibitors capable of targeting multiple proteins with related binding pockets. The core concept is to retain a validated binding scaffold responsible for essential target interactions, while systematically modifying peripheral regions to rapidly access nearby chemical space associated with target variability and functional optimization. We applied this strategy to the 3C-like protease (3CLpro), a conserved enzyme present in multiple coronaviruses and a key target for broad-spectrum antiviral development. Key pharmacophoric features of the SARS-CoV-2 3CLpro inhibitor Leritrelvir were preserved as the core scaffold to maintain critical active-site interactions, while non-essential regions were iteratively transformed within a defined sub-chemical space to generate structurally diverse analogues. Using this, several novel compounds were designed, synthesized and evaluated. Compounds 7c and 7d exhibited potent inhibition of SARS-CoV-2 3CLpro. Notably, compound 7c showed broad-spectrum antiviral activity, maintaining potency comparable to Leritrelvir against β-coronavirus 3CLpro, while demonstrating improved inhibition against α-coronavirus HCoV-NL63 3CLpro. Its anti-SARS-CoV-2 activity was essentially equivalent to Leritrelvir, while its anti-HCoV-NL63 activity was superior. Overall, these results demonstrate that the Transformation strategy is an effective and generalizable framework for scaffold-guided chemical space exploration, particularly suitable for multi-target systems such as viral proteases, where conserved scaffolds maintain baseline activity, while sub-chemical space exploration enables optimization of potency, spectrum coverage, and resistance mitigation.

PMID 42364457
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PubMedClinical drug investigation2026-05-01

Pharmacokinetic Drug-Drug Interaction of Leritrelvir in Healthy Chinese Volunteers: A Single-Arm, Open-Label, Dual-Cohort Study.

Peng Jiao J, Chen Juan J, Du Xiao-Xiao XX, Li Hai-Jun HJ et al.

Preclinical studies have shown that leritrelvir, an anti-coronavirus disease 2019 (COVID-19) drug, is a substrate of CYP3A and P-gp. It also inhibits CYP3A, CYP2C19, and OATP1B3. This study systematically evaluated leritrelvir's pharmacokinetic interactions with sensitive substrates, inhibitors, or inducers of the aforementioned metabolic pathways. The short-term safety of co-administration was also assessed. We conducted a phase Ⅰ, single-arm, open-label, dual-cohort clinical trial in healthy Chinese adults. Cohort 1 evaluated the effect of multiple doses of leritrelvir on the pharmacokinetics of midazolam, omeprazole, and rosuvastatin. Serial blood samples were collected for the determination of midazolam and omeprazole concentrations at pre-dose and post-dose on days 1-2 (midazolam and omeprazole alone) and days 10-11 (midazolam and omeprazole co-administered with leritrelvir). For rosuvastatin, blood samples were collected at pre-dose and post-dose on days 3-6 (rosuvastatin alone) and days 12-15 (rosuvastatin co-administered with leritrelvir). Cohort 2 assessed the effect of multiple dose administration of verapamil and rifampicin on the pharmacokinetics of leritrelvir. Serial blood samples were collected for the determination of leritrelvir concentrations at pre-dose and post-dose on days 1-4 (leritrelvir alone), days 9-12(leritrelvir co-administered with verapamil), and days 28-31(leritrelvir co-administered with rifampicin). In cohort 1, leritrelvir minimally affected omeprazole and rosuvastatin exposure. The geometric mean ratios (GMRs) for their area under the plasma concentration-time curve from time zero to the lowest detectable plasma concentration (AUC0-t) were 98.3% and 113.2%, respectively, versus administration alone. In contrast, leritrelvir increased midazolam AUC0-t to 232.1% (GMR) versus administration alone. In cohort 2, verapamil increased leritrelvir AUC0-t to 251.8% (GMR) versus administration alone. Rifampicin decreased leritrelvir AUC0-t to 80.6% (GMR). The potential for drug-drug interactions between leritrelvir and CYP2C19 or OATP1B3 is low. The same applies to its interaction with a CYP3A inducer. However, as a moderate CYP3A inhibitor, leritrelvir requires caution when co-administered with CYP3A substrates, especially those with a narrow therapeutic index. Although moderate inhibitors of CYP3A and P-gp increased the leritrelvir exposure, this increase may not require dose adjustment on the basis of the phase I PK data of leritrelvir. NCT06031454.

PMID 42062754
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PubMedAntiviral research2026-02-19

The potential of leritrelvir repositioning for the treatment of coxsackievirus B4 and common enterovirus infections.

Liu Qian Q, Tang Bizhen B, Xuan Xianglin X, Wang Huan H et al.

Enteroviruses (EVs) pose major threats to human health, among which coxsackievirus B4 (CVB4) is particularly notable for its high lethality, increasing prevalence, and the absence of approved targeted therapeutics. Leritrelvir, an approved coronavirus disease 2019 (COVID-19) drug targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease (3CLpro), was investigated for repurposing due to structural and functional homology between the EV 3C protease (3Cpro) and SARS-CoV-2 3CLpro. Molecular docking analyses demonstrated that leritrelvir binds to the CVB4 3Cpro active site in a manner similar to that observed for SARS-CoV-2 3CLpro. In vitro experiments showed that leritrelvir inhibited CVB4 replication in HeLa cells, with a half-maximal effective concentration (EC50) of 12.64 nM. The half-maximal cytotoxic concentration (CC50) of leritrelvir in HeLa cells was 572.7 μM, yielding a selectivity index (SI=CC50/EC50) of 4.53 × 104. Among 3-day-old ICR mice infected with CVB4, leritrelvir suppressed viral replication in a dose-dependent manner. Administration of leritrelvir (12 mg/kg/day) prevented mortality, alleviated clinical symptoms and weight loss, and attenuated histopathological lesions in virus-targeted organs (e.g., brain, lungs, myocardium, and small intestine). Additionally, leritrelvir effectively suppressed CVB4-induced elevation of interleukin-6. Leritrelvir exhibited superior anti-CVB4 efficacy both in vitro and in vivo compared with the reference drug fluoxetine. Potent activity was observed against CVB4 clinical isolates and 3Cpro mutants, confirming broad-spectrum efficacy against CVB4 variants. In vitro and in silico analyses revealed that leritrelvir exerted robust antiviral effects against EVA71, CVA16, and human rhinovirus 2. These findings support the repurposing potential of leritrelvir against CVB4 and common EVs.

PMID 41707713
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PubMedBritish journal of clinical pharmacology2026-01-31

Tolerability and pharmacokinetics of leritrelvir in Chinese participants with severe renal impairment and healthy matched control subjects.

Zhou Zi-Yi ZY, Wen Xiao-Qing XQ, Zhang Wen-Rui WR, Huang Yue-Yuan YY et al.

The study's aim is to evaluate the pharmacokinetics (PK) and safety of leritrelvir, a novel 3-chymotrypsin-like cysteine protease (3CLpro) inhibitor, in patients with severe renal impairment (RI; n = 7) compared to healthy controls (n = 8). This nonrandomized, open-label, parallel-group, single-dose trial included primary PK endpoints (Cmax, AUC0-t, AUC0-∞, t1/2) and safety endpoints (AEs, vital signs, laboratory tests). Log-transformed PK parameters were analysed by ANOVA to calculate GMRs (90% confidence intervals [CIs]) for group comparisons, with statistical significance assessed for exposure differences. PK analysis revealed similar median time-to-peak concentration (Tmax) but a reduced elimination half-life (t1/2) in the RI group (4.20 h vs. 5.09 h). The geometric mean ratios (90% CI) of systemic exposure parameters indicated increases of 30.34% for Cmax, 54.19% for AUC0-t, and 56.83% for AUC0-∞ in the RI group compared to controls. Modest PK alterations in severe renal impairment are clinically insignificant given leritrelvir's wide therapeutic index. The drug is well-tolerated (mild-to-moderate, short-duration AEs), and no dose adjustment is needed for patients with renal impairment.

PMID 41617220
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PubMedExpert opinion on therapeutic patents2025-12-05

A patent review of Mpro protease inhibitors for the treatment of COVID-19 infections (2020 - present).

Mik Václav V, Benz Laila S LS, Voller Jiří J, Dunzendorfer-Matt Theresia T et al.

The SARS-CoV-2 main protease (Mpro, also known as 3CLpro or nsp5) is essential for viral replication. As there are no close human homologs, it represents an attractive and specific target for antiviral therapy against COVID-19. Its well-defined active site and conserved substrate specificity have enabled structure-guided drug design with high precision. This review examines the patent landscape for small-molecule inhibitors of SARS-CoV-2 Mpro published between 2020 and early 2025. Compounds were grouped by scaffold type and mechanism of action, covering covalent and non-covalent inhibitors, orthosteric and allosteric binders and unique modalities such as PROTACs. Clinically advanced agents including nirmatrelvir, ensitrelvir, simnotrelvir, zevotrelvir and leritrelvir are highlighted alongside structurally novel leads and broad-spectrum candidates. A number of Mpro inhibitors have progressed into preclinical and clinical stages, underscoring the rapid advancement in this field. The accumulation of structural knowledge, chemical diversity and mechanistic insight has laid a robust foundation for future antiviral development and may further enhance the utility of Mpro inhibitors against evolving coronaviruses.

PMID 41348159
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PubMedAntimicrobial agents and chemotherapy2024-12-17

Single-dose tolerability and pharmacokinetics of leritrelvir in Chinese patients with hepatic impairment and healthy matched controls.

Li Cuiyun C, Mai Jiajia J, Wu Min M, Zhang Hong H et al.

This study evaluated the safety and pharmacokinetics (PK) of a single dose of leritrelvir, a novel inhibitor of 3-chymotrypsin-like cysteine protease (3CLpro), in patients with hepatic impairment versus healthy participants with normal hepatic function. Eight participants with mild (Child-Pugh A) hepatic impairment, eight with moderate (Child-Pugh B) hepatic impairment, and eight healthy matched control participants were enrolled in this open-label, parallel clinical trial. After administration of leritrelvir of 400 mg, PK parameters were calculated and compared across groups. In total, 24 participants were enrolled and completed the study. Leritrelvir was generally well tolerated, with no serious adverse events or deaths reported during the study. Compared to the group with normal hepatic function, the geometric least-squares mean ratios (90% confidence intervals) for Cmax, AUC0-t, and AUC0-∞ of leritrelvir in participants with mild hepatic impairment were 96.9% (69.3%, 135%), 92.2% (69.6%, 122%), and 92.1% (69.7%, 122%), respectively. For moderate hepatic impairment, the corresponding ratios were 91.6% (61.7%, 136%), 113% (80.0%, 160%), and 113% (80.0%, 159%). Leritrelvir exposures were comparable among the three groups. Overall, there was no clinically relevant difference in leritrelvir exposure in participants with hepatic impairment compared to normal controls. No dose adjustment is required for leritrelvir in patients with mild or moderate hepatic impairment.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT06161259.

PMID 39688408
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