Deuremidevir

Deuremidevir
Clinical data
Trade names	民得维
Other names	VV116, JT001, mindeudesivir, renmindevir
Routes of; administration	oral
Legal status
Legal status	US: Investigational drug; CN: conditially Rx;
Identifiers
	IUPAC name [(2R,3R,4R,5R)-5-(4-amino-5-deuteriopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-bis(2-methylpropanoyloxy)oxolan-2-yl]methyl 2-methylpropanoate;
CAS Number	2647442-33-7;
PubChem CID	163358784;
ChemSpider	115285279;
UNII	MF2PS6XPS4;
Chemical and physical data
Formula	C24H30DN5O7
Molar mass	502.546 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES [2H]c2cc([C@]1(C#N)O[C@H](COC(=O)C(C)C)[C@@H](OC(=O)C(C)C)[C@H]1OC(=O)C(C)C)n3ncnc(N)c23;
	InChI InChI=InChI=1S/C24H31N5O7/c1-12(2)21(30)33-9-16-18(34-22(31)13(3)4)19(35-23(32)14(5)6)24(10-25,36-16)17-8-7-15-20(26)27-11-28-29(15)17/h7-8,11-14,16,18-19H,9H2,1-6H3,(H2,26,27,28)/t16-,18-,19-,24+/m1/s1/i7D; Key:RVSSLHFYCSUAHY-QXMJNOOVSA-N;

Deuremidevir, also known as VV116, is a nucleoside analogue antiviral drug. It is administrated through oral tablets, which contain the hydrobromide salt of this drug.^[1]

The drug is a deuterated tri-isobutyrate of GS-441524, the active metabolite of remdesivir. It was first described in a November 2020 preprint by a team including members of Wuhan Institute of Virology and Vigonvita.^[2] It completed a phase 3 trial in 2022.^[3] Results from a separate Phase 3 trial conducted in mainland China from October 2022 to January 2023 suggested that deuremidevir may shorten the duration of COVID-19 symptoms in non-hospitalized adults with mild-to-moderate disease compared to placebo.^[4] Junshi, which markets the drug, received conditional approval from China's National Medical Products Administration in January 2023.^[5]^[6]

In November 2023, in response to viral mutations and changing characteristics of infection, the WHO adjusted its treatment guidelines. Among other changes, the use of deuremidevir was recommended against, except for clinical trials.^[7]

Research

In preclinical studies, a single high dose of the drug (at least 1.0 g/kg) was shown to be tolerated in rats and dogs.^[8]

References

^ Zhu KW (September 2023). "Deuremidevir and Simnotrelvir-Ritonavir for the Treatment of COVID-19". ACS Pharmacology & Translational Science. 6 (9): 1306–1309. doi:10.1021/acsptsci.3c00134. PMC 10496140. PMID 37705591.
^ Yin W, Luan X, Li Z, Xie Y, Zhou Z, Liu J, et al. (November 2020). "Structural basis for repurpose and design of nucleoside drugs for treating COVID-19". bioRxiv. doi:10.1101/2020.11.01.363812. S2CID 226263471.
^ Cao Z, Gao W, Bao H, Feng H, Mei S, Chen P, et al. (February 2023). "VV116 versus Nirmatrelvir-Ritonavir for Oral Treatment of Covid-19". The New England Journal of Medicine. 388 (5): 406–417. doi:10.1056/NEJMoa2208822. PMC 9812289. PMID 36577095.
^ Fan X, Dai X, Ling Y, Wu L, Tang L, Peng C, et al. (February 2024). "Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study". The Lancet Infectious Diseases. 24 (2): 129–139. doi:10.1016/S1473-3099(23)00577-7. PMID 38006892.
^ Devarasetti H (2023-01-30). "China's NMPA conditionally approves two oral drugs for Covid-19". Pharmaceutical Technology. Retrieved 2023-02-04.
^ Liu W, Zhang M, Hu C, Song H, Mei Y, Liu Y, et al. (November 2023). "Remdesivir Derivative VV116 Is a Potential Broad-Spectrum Inhibitor of Both Human and Animal Coronaviruses". Viruses. 15 (12): 2295. doi:10.3390/v15122295. PMC 10748125. PMID 38140536.
^ "WHO updates its guidance on treatments for COVID-19". BMJ (Press release). 9 November 2023.
^ Xie Y, Yin W, Zhang Y, Shang W, Wang Z, Luan X, et al. (November 2021). "Design and development of an oral remdesivir derivative VV116 against SARS-CoV-2". Cell Research. 31 (11): 1212–1214. doi:10.1038/s41422-021-00570-1. PMC 8477624. PMID 34584244.

[Zhu23-1] Zhu KW (September 2023). "Deuremidevir and Simnotrelvir-Ritonavir for the Treatment of COVID-19". ACS Pharmacology & Translational Science. 6 (9): 1306–1309. doi:10.1021/acsptsci.3c00134. PMC 10496140. PMID 37705591.

[2] Yin W, Luan X, Li Z, Xie Y, Zhou Z, Liu J, et al. (November 2020). "Structural basis for repurpose and design of nucleoside drugs for treating COVID-19". bioRxiv. doi:10.1101/2020.11.01.363812. S2CID 226263471.

[3] Cao Z, Gao W, Bao H, Feng H, Mei S, Chen P, et al. (February 2023). "VV116 versus Nirmatrelvir-Ritonavir for Oral Treatment of Covid-19". The New England Journal of Medicine. 388 (5): 406–417. doi:10.1056/NEJMoa2208822. PMC 9812289. PMID 36577095.

[pmid38006892-4] Fan X, Dai X, Ling Y, Wu L, Tang L, Peng C, et al. (February 2024). "Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study". The Lancet Infectious Diseases. 24 (2): 129–139. doi:10.1016/S1473-3099(23)00577-7. PMID 38006892.

[5] Devarasetti H (2023-01-30). "China's NMPA conditionally approves two oral drugs for Covid-19". Pharmaceutical Technology. Retrieved 2023-02-04.

[pmid38140536-6] Liu W, Zhang M, Hu C, Song H, Mei Y, Liu Y, et al. (November 2023). "Remdesivir Derivative VV116 Is a Potential Broad-Spectrum Inhibitor of Both Human and Animal Coronaviruses". Viruses. 15 (12): 2295. doi:10.3390/v15122295. PMC 10748125. PMID 38140536.

[7] "WHO updates its guidance on treatments for COVID-19". BMJ (Press release). 9 November 2023.

[8] Xie Y, Yin W, Zhang Y, Shang W, Wang Z, Luan X, et al. (November 2021). "Design and development of an oral remdesivir derivative VV116 against SARS-CoV-2". Cell Research. 31 (11): 1212–1214. doi:10.1038/s41422-021-00570-1. PMC 8477624. PMID 34584244.

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