Other substances

N3

A tripeptide SARS-CoV-2 3C-like protease inhibitor.

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

N3 is a SARS-CoV-2 3C-like protease covalent inhibitor with anti-SARS-CoV-2 properties (Jin et al., 2020).

N3 on PubChem

Synonyms

Inhibitor N3; E)-(4S,6S)-8-Methyl-6-((S)-3-methyl-2-{(S)-2-[(5-methyl-isoxazole-3-carbonyl)-amino]-propionylamino}-butyrylamino)-5-oxo-4-((R)-2-oxo-pyrrolidin-3-ylmethyl)-non-2-enoic acid benzyl ester

CC1=CC(=NO1)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@@H]2CCNC2=O)/C=C/C(=O)OCC3=CC=CC=C3

Supporting references

Link	Tested on	Impact factor	Notes	Publication date
Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors 3CLpro Crystallization Enzyme assay In vitro In silico	in silico; in vitro enzyme assay; crystallization; Vero E6 cells	42.78	Computationally predicted to form a covalent bond with the SARS-CoV-2 3C-like protease's active site. This bond was experimentally observed after co-crystallization of the compound with the protease. N3 inhibited SARS-CoV-2 infection in Vero E6 cells with EC50 of ca. 16.77 μM.	Jun/11/2020

AI-suggested references

Link	Publication date
Identifying the natural compound Catechin from tropical mangrove plants as a potential lead candidate against 3CLpro from SARS-CoV-2: An integrated in silico approach.	Oct/13/2021
Potential anti-viral activity of approved repurposed drug against main protease of SARS-CoV-2: an in silico based approach.	Apr/06/2022
First COVID-19 molecular docking with a chalcone-based compound: synthesis, single-crystal structure and Hirshfeld surface analysis study.	Mar/04/2021
Discovery of potent inhibitors for SARS-CoV-2's main protease by ligand-based/structure-based virtual screening, MD simulations, and binding energy calculations.	Mar/16/2021
Covalent and non-covalent binding free energy calculations for peptidomimetic inhibitors of SARS-CoV-2 main protease.	Mar/12/2021
Potential of 24-Propylcholestrol as Immunity Inducer against Infection of COVID-19 Virus: In Silico Study Immunomodulatory Drugs.	Dec/05/2022
Interactions Between Remdesivir, Ribavirin, Favipiravir, Galidesivir, Hydroxychloroquine and Chloroquine with Fragment Molecular of the COVID-19 Main Protease with Inhibitor N3 Complex (PDB ID:6LU7) Using Molecular Docking.	Dec/16/2020
In silico analysis of marine natural product from sponge (Clathria Sp.) for their activity as inhibitor of SARS-CoV-2 Main Protease.	Aug/02/2021
Pomegranate peel polyphenols prophylaxis against SARS-CoV-2 main protease by in-silico docking and molecular dynamics study.	Sep/27/2021
Computational studies on the design of NCI natural products as inhibitors to SARS-CoV-2 main protease.	Mar/25/2022
Phytonutrient Inhibitors of SARS-CoV-2/NSP5-Encoded Main Protease (Mpro) Autocleavage Enzyme Critical for COVID-19 Pathogenesis.	Apr/01/2022
In Silico Drug Repositioning to Target the SARS-CoV-2 Main Protease as Covalent Inhibitors Employing a Combined Structure-Based Virtual Screening Strategy of Pharmacophore Models and Covalent Docking.	Apr/03/2022
Discovery of a "Cocktail" of Potential SARS-COV-2 Main Protease Inhibitors through Virtual Screening of Known Chemical Components of Vitex negundo L. ("Lagundi").	Jun/22/2021
Natural metabolites from the soft coral Nephthea sp. as potential SARS-CoV-2 main protease inhibitors.	Dec/31/2020
Potential of Ficus microcarpa metabolites against SARS-CoV-2 main protease supported by docking studies.	Sep/01/2021
Identification of potential bioactive natural compounds from Indonesian medicinal plants against 3-chymotrypsin-like protease (3CLpro) of SARS-CoV-2: molecular docking, ADME/T, molecular dynamic simulations, and DFT analysis.	May/27/2020
Evaluation of the effects of chlorhexidine and several flavonoids as antiviral purposes on SARS-CoV-2 main protease: molecular docking, molecular dynamics simulation studies.	Feb/08/2022
Discovery of Potent SARS-CoV-2 Inhibitors from Approved Antiviral Drugs via Docking and Virtual Screening.	Mar/10/2022
Isolation, structural elucidation and molecular docking studies against SARS-CoV-2 main protease of new stigmastane-type steroidal glucosides isolated from the whole plants of Vernonia gratiosa.	Feb/28/2020
In silico discovery of novel inhibitors from Northern African natural products database against main protease (Mpro) of SARS-CoV-2.	Mar/15/2022
Natural Compounds as Inhibitors of SARS-CoV-2 Main Protease (3CLpro): A Molecular Docking and Simulation Approach to Combat COVID-19.	Nov/18/2020
In silico analysis and identification of antiviral coumarin derivatives against 3-chymotrypsin-like main protease of the novel coronavirus SARS-CoV-2	Apr/01/2022
Development of Effective Therapeutic Molecule from Natural Sources against Coronavirus Protease	May/27/2020
Identification of nut protein-derived peptides against SARS-CoV-2 spike protein and main protease	Jan/31/2022
Synthesis of Dihydrobenzofuro[3,2-b]chromenes as Potential 3CLpro Inhibitors of SARS-CoV-2: A Molecular Docking and Molecular Dynamics Study	Feb/16/2022
Computational Screening of Phenylamino-Phenoxy-Quinoline Derivatives against the Main Protease of SARS-CoV-2 Using Molecular Docking and the ONIOM Method	Sep/22/2021
Depicting the inhibitory potential of polyphenols from Isatis indigotica root against the main protease of SARS CoV-2 using computational approaches	Dec/09/2020
Inhibitor binding influences the protonation states of histidines in SARS-CoV-2 main protease	Nov/26/2020
A microscopic description of SARS-CoV-2 main protease inhibition with Michael acceptors. Strategies for improving inhibitor design	Feb/23/2021
New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity Aspects.	Sep/11/2021
Identification of Alkaloids from Terminalia chebula as Potent SARS- CoV-2 Main Protease Inhibitors: An In Silico Perspective.	Apr/11/2022
Alkamides and Piperamides as Potential Antivirals against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).	Aug/25/2020
Withanone and caffeic acid phenethyl ester are predicted to interact with main protease (Mpro) of SARS-CoV-2 and inhibit its activity	Oct/16/2021
In silico studies on structural inhibition of SARS-CoV-2 main protease Mpro by major secondary metabolites of Andrographis paniculata and Cinchona officinalis	Oct/27/2021
Evaluation of green tea polyphenols as novel corona virus (SARS CoV-2) main protease (Mpro) inhibitors - an in silico docking and molecular dynamics simulation study	Jun/22/2020
Potential of coronavirus 3C-like protease inhibitors for the development of new anti-SARS-CoV-2 drugs: Insights from structures of protease and inhibitors	Jun/11/2020
Repurposing drugs and identification of inhibitors of integral proteins (spike protein and main protease) of SARS-CoV-2	Apr/15/2020
Intranasal Coronavirus SARS-CoV-2 Immunization with Lipid Adjuvants Provides Systemic and Mucosal Immune Response against SARS-CoV-2 S1 Spike and Nucleocapsid Protein	Mar/25/2022
A possible potential COVID-19 drug candidate: Diethyl 2-(2-(2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetyl)hydrazono)malonate: Docking of disordered independent molecules of a novel crystal structure, HSA/DFT/XRD and cytotoxicity	Nov/28/2021
Fragment Molecular Orbital Based Interaction Analyses on COVID-19 Main Protease - Inhibitor N3 Complex (PDB ID: 6LU7)	Jun/25/2020
SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma	Apr/08/2021
In silico identification of potential inhibitors against main protease of SARS-CoV-2 6LU7 from Andrographis panniculata via molecular docking, binding energy calculations and molecular dynamics simulation studies	Dec/31/2020
SARS-CoV-2 main protease inhibition by compounds isolated from Luffa cylindrica using molecular docking.	Mar/19/2021
Computational insights into tetracyclines as inhibitors against SARS-CoV-2 Mpro via combinatorial molecular simulation calculations	Jul/09/2020
The potential effects of clinical antidiabetic agents on SARS-CoV-2	Apr/20/2020
Design, Microwave-Assisted Synthesis and In Silico Prediction Study of Novel Isoxazole Linked Pyranopyrimidinone Conjugates as New Targets for Searching Potential Anti-SARS-CoV-2 Agents	Oct/10/2021
Evaluation of SARS-CoV-2 main protease and inhibitor interactions using dihedral angle distributions and radial distribution function	Nov/16/2021
Repurposing of known anti-virals as potential inhibitors for SARS-CoV-2 main protease using molecular docking analysis.	Apr/30/2020
Mechanism of inhibition of SARS-CoV-2 Mpro by N3 peptidyl Michael acceptor explained by QM/MM simulations and design of new derivatives with tunable chemical reactivity	Nov/27/2020
Discovery of potent Covid-19 main protease inhibitors using integrated drug-repurposing strategy	Apr/14/2021
Investigation of angucycline compounds as potential drug candidates against SARS Cov-2 main protease using docking and molecular dynamic approaches	Apr/10/2021
COVID-19: inflammatory responses, structure-based drug design and potential therapeutics	Aug/20/2020
Reckoning a fungal metabolite, Pyranonigrin A as a potential Main protease (Mpro) inhibitor of novel SARS-CoV-2 virus identified using docking and molecular dynamics simulation	Jul/06/2020
In silico evaluation of the compounds of the ayurvedic drug, AYUSH-64, for the action against the SARS-CoV-2 main protease	Feb/25/2021
In-silico drug repurposing for targeting SARS-CoV-2 main protease (Mpro)	Feb/06/2022
Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 (COVID-19) through Computational Drug Repurposing Study	Mar/25/2022
Identification of potential plant-based inhibitor against viral proteases of SARS-CoV-2 through molecular docking, MM-PBSA binding energy calculations and molecular dynamics simulation.	Apr/15/2021
SARS-COV-2 Mpro conformational changes induced by covalently bound ligands	Jun/12/2020
SARS-CoV and SARS-CoV-2 main protease residue interaction networks change when bound to inhibitor N3	Apr/08/2022
Calendulaglycoside A Showing Potential Activity Against SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and SAR Studies.	May/17/2021
Structure-property relationship in thioxotriaza-spiro derivative: Crystal structure and molecular docking analysis against SARS-CoV-2 main protease	Oct/17/2021
Potential bioactive compounds as SARS-CoV-2 inhibitors from extracts of the marine red alga Halymenia durvillei (Rhodophyta) - A computational study.	Aug/23/2021
Are vanadium complexes druggable against the main protease Mpro of SARS-CoV-2? - A computational approach.	Feb/11/2021
In silico Analysis Revealed Potential Anti-SARS-CoV-2 Main Protease Activity by the Zonulin Inhibitor Larazotide Acetate	Sep/30/2021
Molecular mechanism of inhibition of COVID-19 main protease by beta-adrenoceptor agonists and adenosine deaminase inhibitors using in silico methods	Jul/06/2020
Structural insight into the recognition of S-adenosyl-L-homocysteine and sinefungin in SARS-CoV-2 Nsp16/Nsp10 RNA cap 2'-O-Methyltransferase.	Oct/01/2020
In-Silico approach for identification of effective and stable inhibitors for COVID-19 main protease (Mpro) from flavonoid based phytochemical constituents of Calendula officinalis	Apr/05/2022
Viral 3CLpro as a Target for Antiviral Intervention Using Milk-Derived Bioactive Peptides	Jan/29/2022
Identification of potential molecules against COVID-19 main protease through structure-guided virtual screening approach	Sep/03/2021
Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2	Oct/23/2021
Computational screening for potential drug candidates against the SARS-CoV-2 main protease.	Aug/04/2020
Structural modification of antineoplastic drug carmofur designed to the inhibition of SARS-CoV-2 main protease: A theoretical investigation	Dec/09/2021
Theobroma cacao L. compounds: Theoretical study and molecular modeling as inhibitors of main SARS-CoV-2 protease.	May/24/2021
Potential inhibitors of the main protease of SARS-CoV-2 and modulators of arachidonic acid pathway: Non-steroidal anti-inflammatory drugs against COVID-19.	Jul/29/2021
Molecular docking reveals the potential of Salvadora persica flavonoids to inhibit COVID-19 virus main protease	May/21/2020
Investigating the structure-activity relationship of marine natural polyketides as promising SARS-CoV-2 main protease inhibitors	Sep/22/2021
Molecular dynamics simulation of docking structures of SARS-CoV-2 main protease and HIV protease inhibitors.	Aug/23/2020

Clinical trials

ID	Title	Status	Start date	Completion date
NCT04924842	COVID-19 - SARS-CoV-2 Community Contamination in Children and Adults - Impact of Variants (Dyn3CEA - Nosocor Phase 2)	Completed	Jun/22/2021	Oct/28/2021
Alternative id - 69HCL21_0564 Interventions - Other: Review of medical file\|Other: Phone call interview Study type - Observational Study results - No Results Available Locations - Hôpital Femme Mère et enfant, Lyon, Auvergne Rhône Alpes, France Study designs - Observational Model: Case-Only\|Time Perspective: Prospective Enrollment - 87 Age - Child, Adult, Older Adult Outcome measures - Percentage of possible contaminants, adults, adolescents and children with Covid-19
NCT04664296	COVID-19 - SARS-CoV-2 Community Contamination in Children and Adults (Dyn3CEA_Nosocor)	Completed	Dec/21/2020	Mar/23/2021
Alternative id - 69HCL20_1100 Interventions - Other: Review of medical patient file\|Other: Phone call interview Study type - Observational Study results - No Results Available Locations - Service de Reanimation Pediatrique, Lyon, Rhone, France Study designs - Observational Model: Case-Only\|Time Perspective: Prospective Enrollment - 72 Age - Child, Adult, Older Adult Outcome measures - Percentage of possible contaminants, adults, adolescents and children with Covid-19

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