Other substances

N(4)-Hydroxycytidine

A ribonucleoside analogue.

Phase of research

Potential treatment - pre-clinical evidence

How it helps

Antiviral

Drug status

Experimental

Supporting references

Contradictory references

AI-suggested references

Clinical trials

General information

β-D-N4-hydroxycytidine is orally bioavailable ribonucleoside analogue, which displays antiviral activity against a broad spectrum of RNA viruses, including coronaviruses, by introducing mutations into the nascent replicated RNA. It is the active metabolite of the EIDD-2801 prodrug (Sheahan et al., 2020).

N(4)-Hydroxycytidine on DrugBank
N(4)-Hydroxycytidine on PubChem

Synonyms

NHC; Beta-D-N4-hydroxycytidine; EIDD-1931

C1=CN(C(=O)N=C1NO)[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O

Supporting references

Link	Tested on	Impact factor	Notes	Publication date
Repurposing Nucleoside Analogs for Human Coronaviruses Small molecule In vitro	PBM and CEM cells (cytotoxicity only), Huh-7 cells; Vero CCL-81 cells; RD cells; Caco-2 cells; Calu3 cells; SARS-CoV-2 (NR-52281: USA-WA/2020)	4.68	Inhibits SARS-CoV-2 in vitro. It could be cytotoxic in low-micromolar range, however.	Oct/29/2020
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice Small molecule In vitro	Vero cells; Calu-3 cells; primary human epithelial cells; SARS-CoV-2 strain 2019-nCoV/USA-WA1/2020	16.30	The compound inhibited SARS-CoV-2 infection in Vero cells with IC50 of 0.3 μM and facilitated dose-dependent reduction of viral titres and viral RNA in Calu-3 cells with IC50 of 0.08 μM and 0.09 μM, respectively.	Apr/29/2020
Molnupiravir promotes SARS-CoV-2 mutagenesis via the RNA template RdRpol Small molecule Enzyme assay In vitro	In vitro	5.16	In vitro enzyme assay data support a model where the drug’s mechanism of action is based on template strand-mediated RNA mutagenesis.	May/11/2021
Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern 3CLpro RdRpol Spike variant Small molecule In vitro	Vero E6(-GFP) cells; SARS-CoV-2 (various strains)	5.97	The compound retains its anti-SARS-CoV-2 activity in vitro against strains Alpha, Beta, Gamma, and Delta.	Jan/24/2021
Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant Spike protein Spike variant Protein factor In vitro Antibody	Vero E6-TMPRSS2 cells; SARS-CoV-2 strains (SARS-CoV-2/UT-NC002-1T/Human/2020/Tokyo, alpha, beta, gamma, delta, omicron)	91.25	The drug retained its anti-SARS-CoV-2 activity against all of the strains tested (WT-like, alpha, beta, gamma, delta, omicron).	Jan/26/2022
Different efficacies of neutralizing antibodies and antiviral drugs on SARS-CoV-2 Omicron subvariants, BA.1 and BA.2 RdRpol Spike variant Small molecule In vitro Antibody	VeroE6/TMPRSS2 cells		The compound displayed anti-SARS-CoV-2 Omicron activity in vitro.	Jul/04/2022

AI-suggested references

Link	Publication date
Role of different tautomers in the base-pairing abilities of some of the vital antiviral drugs used against COVID-19.	Sep/12/2020
PF-07321332 (Nirmatrelvir) Does Not Interact with Human ENT1 or ENT2: Implications for COVID-19 Patients.	May/16/2022
Analysis of hematological indexes of COVID-19 patients from fever clinics in Suzhou, China.	Apr/06/2020
Molnupiravir-A Novel Oral Anti-SARS-CoV-2 Agent.	Oct/23/2021
The Potential Bioactive Components of Nine TCM Prescriptions Against COVID-19 in Lung Cancer Were Explored Based on Network Pharmacology and Molecular Docking	Jan/20/2022
Composition, Clinical Efficiency, and Mechanism of NHC-Approved "Three Chinese Medicines and Three Chinese Recipes" for COVID-19 Treatment	Feb/04/2022
Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity	Aug/20/2021
Remdesivir and EIDD-1931 Interact with Human Equilibrative Nucleoside Transporters 1 and 2: Implications for Reaching SARS-CoV-2 Viral Sanctuary Sites.	Dec/30/2021
A robust SARS-CoV-2 replication model in primary human epithelial cells at the air liquid interface to assess antiviral agents	Jul/17/2021
Significant Inhibition of Porcine Epidemic Diarrhea Virus In Vitro by Remdesivir, Its Parent Nucleoside and beta-D-N4-hydroxycytidine.	Mar/22/2021
Viral polymerase binding and broad-spectrum antiviral activity of molnupiravir against human seasonal coronaviruses.	Oct/02/2021
A density functional theory study on silver and bis-silver complexes with lighter tetrylene: are silver and bis-silver carbenes candidates for SARS-CoV-2 inhibition? Insight from molecular docking simulation	Nov/01/2021
Molnupiravir; molecular and functional descriptors of mitochondrial safety	Dec/06/2021
Decoding molnupiravir-induced mutagenesis in SARS-CoV-2.	Jun/09/2021
Inhibitors of dihydroorotate dehydrogenase cooperate with molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication	Apr/25/2022
beta-D-N 4-hydroxycytidine (NHC) Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells	Apr/29/2020
Metallodrug Profiling against SARS-CoV-2 Target Proteins Identifies Highly Potent Inhibitors of the S/ACE2 interaction and the Papain-like Protease PLpro	Sep/16/2021
Molnupiravir and Its Antiviral Activity Against COVID-19	Oct/22/2021
Pharmacokinetics of ss-d-N4-hydroxycytidine, the parent nucleoside of prodrug molnupiravir, in non-plasma compartments of patients with SARS-CoV-2 infection	Nov/02/2021
Biostructural Models for the Binding of Nucleoside Analogs to SARS-CoV-2 RNA-Dependent RNA Polymerase	Mar/03/2021
Molecular modelling studies unveil potential binding sites on human serum albumin for selected experimental and in silico COVID-19 drug candidate molecules	Apr/19/2022

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