Nirmatrelvir

Summary

Nirmatrelvir (CHEMBL4802135) is an approved small-molecule EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor targeting TAS2R1; indicated across 7 conditions including severe acute respiratory syndrome and pneumonia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 1 (TAS2R1)
• Indications: 7 conditions
• Clinical trials: 59
• Chemistry: 499.5 Da · C23H32F3N5O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4802135
Name	Nirmatrelvir
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	155903259
ChEBI	CHEBI:170007
Molecular formula	C23H32F3N5O4
Molecular weight	499.5
InChIKey	LIENCHBZNNMNKG-OJFNHCPVSA-N

SMILES: CC1([C@@H]2[C@H]1[C@H](N(C2)C(=O)[C@H](C(C)(C)C)NC(=O)C(F)(F)F)C(=O)N[C@@H](C[C@@H]3CCNC3=O)C#N)C

IUPAC name: (1R,2S,5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl]-3-[(2S)-3,3-dimethyl-2-[(2,2,2-trifluoroacetyl)amino]butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide

ChEBI definition: An azabicyclohexane that is (1R,5S)-3-azabicyclo[3.1.0]hexane substituted by {(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}aminoacyl, 3-methyl-N-(trifluoroacetyl)-L-valinamide, methyl and methyl groups at positions 2S, 3, 6 and 6, respectively. It is the first orally administered inhibitor of SARS-CoV-2 main protease developed by Pfizer and used in combination with ritonavir for the treatment of COVID-19.

Pharmacological roles (ChEBI): EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor, anticoronaviral agent.

Also known as: Nirmatrelvir, Nirmatrelvir component of paxlovid, Pf-07321332, PF-07321332, PF07321332, NIRMATRELVIR, Paxlovid, Nirmatrevir, Nirmatrelvir; Lagevrio, Nirtamtrelvir

Patent coverage: 703 distinct patent families (1,262 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
	CoV 3C-like (main) protease	Inhibition	7.48
TAS2R1	TAS2R1	Agonist		0%	Q9NYW7

Broader ChEMBL bioactivity targets: 7 (assay-derived). Sample: Cathepsin K, Cathepsin S, Cathepsin L2, Cytochrome P450 3A4, Replicase polyprotein 1a, Replicase polyprotein 1ab, Replicase polyprotein 1ab.

Bioactivity

ChEMBL activities: 70 potent at pChembl ≥ 5 of 72 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P0DTD1	9.59	Ki	0.26	nM	CHEMBL_ACT_25974561
P0DTD1	9.1	IC50	0.79	nM	CHEMBL_ACT_24720793
P0DTD1	9	Ki	1	nM	CHEMBL_ACT_29132963
P0DTD1	8.52	Ki	3	nM	CHEMBL_ACT_24822814
P0DTD1	8.52	Ki	3	nM	CHEMBL_ACT_24875060
P0DTD1	8.52	Ki	3	nM	CHEMBL_ACT_24977644
P0DTD1	8.52	Ki	3	nM	CHEMBL_ACT_25493993
P0DTD1	8.52	Ki	3	nM	CHEMBL_ACT_25504729
P0DTD1	8.52	Ki	3	nM	CHEMBL_ACT_25516608
P0DTD1	8.52	Ki	3	nM	CHEMBL_ACT_26020171
P0DTD1	8.52	Ki	3	nM	CHEMBL_ACT_26154770
P0DTD1	8.52	Ki	3	nM	CHEMBL_ACT_26160746
P0DTD1	8.52	Ki	3	nM	CHEMBL_ACT_28709123
P0DTD1	8.52	Ki	3	nM	CHEMBL_ACT_29100957
P0DTD1	8.51	Ki	3.11	nM	CHEMBL_ACT_24823699
P0DTD1	8.51	Ki	3.1	nM	CHEMBL_ACT_24842628
P0DTD1	8.51	Ki	3.11	nM	CHEMBL_ACT_24875199
P0DTD1	8.51	Ki	3.11	nM	CHEMBL_ACT_25050992
P0DTD1	8.51	Ki	3.11	nM	CHEMBL_ACT_25061594
P0DTD1	8.51	Ki	3.11	nM	CHEMBL_ACT_25077564
P0DTD1	8.51	IC50	3.1	nM	CHEMBL_ACT_25081268
P0DTD1	8.51	Ki	3.11	nM	CHEMBL_ACT_25457408
P0DTD1	8.51	Ki	3.11	nM	CHEMBL_ACT_25871816
P0DTD1	8.51	Ki	3.1	nM	CHEMBL_ACT_25930824
P0DTD1	8.51	Ki	3.1	nM	CHEMBL_ACT_25974594
P0DTD1	8.51	Ki	3.11	nM	CHEMBL_ACT_26006270
P0DTD1	8.51	Ki	3.11	nM	CHEMBL_ACT_26046126
P0DTD1	8.51	Ki	3.11	nM	CHEMBL_ACT_29174908
P0DTD1	8.44	IC50	3.62	nM	CHEMBL_ACT_26046130
P0DTD1	8.39	Ki	4.04	nM	CHEMBL_ACT_25882613

Target pathways

Aggregated over 1 target gene(s): TAS2R1.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	1	TAS2R1
Signaling by GPCR	1	TAS2R1
GPCR downstream signalling	1	TAS2R1
G alpha (i) signalling events	1	TAS2R1
Class C/3 (Metabotropic glutamate/pheromone receptors)	1	TAS2R1
GPCR ligand binding	1	TAS2R1
Sensory Perception	1	TAS2R1
Sensory perception of taste	1	TAS2R1
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	TAS2R1

Dominant GO biological processes

GO term	Targets
detection of chemical stimulus involved in sensory perception of bitter taste	1
signal transduction	1
G protein-coupled receptor signaling pathway	1
sensory perception of taste	1

Indications & clinical

Indications

7 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
severe acute respiratory syndrome	3	MONDO:0005091	MONDO:0100096
pneumonia	3	MONDO:0005249	EFO:0003106
influenza	3	MONDO:0005812	EFO:0007328
long COVID-19	2	MONDO:0100233	MONDO:0100233
liver disorder	1	MONDO:0005154	EFO:0001421
kidney disorder	1	MONDO:0005240	EFO:0003086

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 59.

Phase distribution

Phase	Trials
PHASE1	16
Not specified	13
PHASE2	12
PHASE3	9
PHASE4	4
PHASE2/PHASE3	3
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06792214	PHASE4	RECRUITING	Antiviral Strategies in the Prevention of Long-term Cardiovascular Outcomes Following COVID-19: The paxloviD/Remdesivir Effectiveness For the prEvention of loNg coviD Clinical Trial
NCT05366192	PHASE4	COMPLETED	The Safety of Paxlovid in Hemodialysis Patients With Covid-19
NCT05690646	PHASE4	UNKNOWN	Prophylactic Effect of Nirmatrelvir/Ritonavir and Ursodeoxycholic Acid on Reducing Complications After Cardiac Surgery
NCT05938140	PHASE4	UNKNOWN	Efficiency and Safety of Paxlovid for COVID-19 Patients With Severe Chronic Kidney Disease
NCT02735707	PHASE3	RECRUITING	Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
NCT04381936	PHASE3	RECRUITING	Randomised Evaluation of COVID-19 Therapy
NCT05261139	PHASE3	RECRUITING	EPIC-Peds: A Study to Learn About the Study Medicine Called PF-07321332 (Nirmatrelvir)/Ritonavir in Patients Under 18 Years of Age With COVID-19 That Are Not Hospitalized But Are at Risk for Severe Disease
NCT05614349	PHASE3	ACTIVE_NOT_RECRUITING	Canadian Adaptive Platform Trial of Treatments for COVID-19 in Community Settings
NCT05852873	PHASE3	ACTIVE_NOT_RECRUITING	PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway
NCT04960202	PHASE2/PHASE3	COMPLETED	EPIC-HR: Study of Oral PF-07321332/Ritonavir Compared With Placebo in Nonhospitalized High Risk Adults With COVID-19
NCT05011513	PHASE2/PHASE3	TERMINATED	Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients (EPIC-SR).
NCT05047601	PHASE2/PHASE3	COMPLETED	A Study of a Potential Oral Treatment to Prevent COVID-19 in Adults Who Are Exposed to Household Member(s) With a Confirmed Symptomatic COVID-19 Infection
NCT05321394	PHASE3	COMPLETED	Non-inferiority Trial on Treatments in Early COVID-19
NCT05341609	PHASE3	COMPLETED	Efficacy and Safety of JT001 (VV116) Compared With Paxlovid
NCT05601167	PHASE3	COMPLETED	Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population
NCT05682586	PHASE3	UNKNOWN	UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients
NCT04746183	PHASE1/PHASE2	RECRUITING	AGILE (Early Phase Platform Trial for COVID-19)
NCT05041907	PHASE2	RECRUITING	Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)
NCT05587894	PHASE2	RECRUITING	OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial
NCT07157007	PHASE2	RECRUITING	Early-stage Trial to Determine a Safe and Effective Dose for Ratutrelvir in Patients With Mild to Moderate COVID-19
NCT07406217	PHASE2	RECRUITING	OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients
NCT07597902	PHASE2	NOT_YET_RECRUITING	SARS-CoV-2 and Herpesvirus Inhibition for Ending Long COVID Dysfunction
NCT05438602	PHASE2	COMPLETED	A Study to Learn About the Study Medicines (Nirmatrelvir Plus Ritonavir) in People Aged 12 Years or Older With COVID-19 and a Compromised Immune System
NCT05545319	PHASE2	WITHDRAWN	A Study to Learn About the Medicine Called Nirmatrelvir Used in Combination With Ritonavir in People With Weakened Immune Systems or at Increased Risk for Poor Outcomes Who Are Hospitalized Due to Severe COVID-19
NCT05567952	PHASE2	COMPLETED	A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir
NCT05576662	PHASE2	COMPLETED	Paxlovid for Treatment of Long Covid
NCT05668091	PHASE2	COMPLETED	A Decentralized, Randomized Phase 2 Efficacy and Safety Study of Nirmatrelvir/Ritonavir in Adults with Long COVID.
NCT05823896	PHASE2	COMPLETED	ImPROving Quality of LIFe in the Long COVID Patient
NCT05965726	PHASE2	COMPLETED	RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms
NCT04909853	PHASE1	COMPLETED	Renal Impairment Study of PF-07321332 Boosted With Ritonavir in Adult Participants With Renal Impairment and in Healthy Participants With Normal Renal Function.
NCT04962022	PHASE1	COMPLETED	Drug-Drug Interaction Study Assessing Effect of Itraconazole on PF-07321332/Ritonavir in Healthy Participants
NCT04962230	PHASE1	COMPLETED	Drug-Drug Interaction Study Assessing Effect of Carbamazepine on PF-07321332 Boosted With Ritonavir
NCT05005312	PHASE1	COMPLETED	Study to Estimate the Effects of Hepatic Impairment on the Pharmacokinetics (PK) of PF-07321332
NCT05032950	PHASE1	COMPLETED	Drug-Drug Interaction Study to Estimate the Effect of PF-07321332/Ritonavir and Ritonavir on Midazolam in Healthy Participants
NCT05064800	PHASE1	COMPLETED	PF-07321332/Ritonavir and Ritonavir on Dabigatran Study in Healthy Participants
NCT05129475	PHASE1	COMPLETED	Food Effect Study to Evaluate the Effect of High-Fat Meal on the Relative Bioavailability of PF-07321332 Boosted With Ritonavir in Healthy Adult Participants
NCT05263895	PHASE1	COMPLETED	Relative Bioavailability Study of 4 Different Formulations of PF-07321332 Relative to the Commercial Tablet Formulation
NCT05263921	PHASE1	COMPLETED	Relative Bioavailability Study of PF-07321332/Ritonavir Oral Powder Relative to the Commercial Tablets in Healthy Participants
NCT05339334	PHASE1	COMPLETED	A Study to Learn About the Study Medicine PF-07321332 and Ritonavir in Adult Healthy Chinese Participants.
NCT05386472	PHASE1	TERMINATED	A Study to Learn About the Study Medicine (Nirmatrelvir Plus Ritonavir) in Pregnant Women With COVID-19

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

1 molecules share ≥1 primary target. Top 1 by shared-target count:

Molecule	Source	Status	Shared targets
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	TAS2R1