Other substances

Nafamostat mesylate

A serine protease inhibitor.

Phase of research

Potential treatment - pre-clinical evidence

How it helps

Antiviral

Drug status

Used to treat other disease

Supporting references

Contradictory references

AI-suggested references

Clinical trials

General information

Nafamostat mesylate is inhibits a broad-spectrum of serine proteases. It has anti-inflammatory, anticoagulant, mucus clearing, and potential antiviral activities. Nafamostat mesylate might inhibit the activity of transmembrane protease serine 2 (TMPRSS2), which mediates viral cell entry for SARS-CoV-2, thereby inhibiting viral infection (NCIt).

Nafamostat mesylate on DrugBank
Nafamostat mesylate on PubChem
Nafamostat mesylate on Wikipedia

Marketed as

BERABU; BUIPEL; BUSERON; COAHIBITOR; FAMOSET; FUTHAN; NAFASTON; NAFATAT; NAMOSTATT; NAOTAMIN; OPSUN; PATHRON; RONASTAT

CS(=O)(=O)O.CS(=O)(=O)O.C1=CC(=CC=C1C(=O)OC2=CC3=C(C=C2)C=C(C=C3)C(=N)N)N=C(N)N

Supporting references

Link	Tested on	Impact factor	Notes	Publication date
Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro	VERO E6 cell cultures		Blocked virus infection at low-micromolar concentration	Feb/04/2020
The anticoagulant nafamostat potently inhibits SARS-CoV-2 infection in vitro: an existing drug with multiple possible therapeutic effects Preprint	lung epithelium-derived Calu-3 cells		10-fold more active than camostat mesylate	Apr/23/2020
Systemic in Silico Screening in Drug Discovery for Coronavirus Disease (COVID-19) with an Online Interactive Web Server	in silico	4.55	Predicted to bind a SARS-CoV-2 protein structural feature.	Aug/11/2020
Comparative analysis of antiviral efficacy of FDA‐approved drugs against SARS‐CoV‐2 in human lung cells Small molecule In vitro	Calu-3 human airway epithelial cells	2.02	Displayed strong antiviral activity in human lung cells in vitro.	Aug/07/2020
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing Small molecule	in silico	42.78		Apr/30/2020
SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles Preprint	CaCo-2 cells		limited activity	Apr/05/2020
Comparative analysis of antiviral efficacy of FDA-approved drugs against SARS-CoV-2 in human lung cells: Nafamostat is the most potent antiviral drug candidate Preprint	Calu-3 human airway epithelial cells		the most potent antiviral activities in human lung cells, lower IC50 value in Calu-3 cells than VERO E6 cells	May/12/2020
Clinical improvement in a patient with severe coronavirus disease 2019 after administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate Severe severity Small molecule Case report	Patient	1.72	Used as an anticoagulant in continuous hemodiafiltration in parallel with hydroxychloroquine treatment. Clinical improvement in a severe COVID-19 patient not responding to the lopinavir/ritonavir therapy. Dosage: 0.2–0.4 mg/kg/hr.	Aug/06/2020
An Enzymatic TMPRSS2 Assay for Assessment of Clinical Candidates and Discovery of Inhibitors as Potential Treatment of COVID-19 Preprint	in vitro			Jun/23/2020
Structural Insights into the Binding Modes of Viral RNA-Dependent RNA Polymerases Using a Function-Site Interaction Fingerprint Method for RNA Virus Drug Discovery RdRpol Small molecule In silico	in silico	4.07	Predicted to inhibit the SARS-CoV-2 RNA-dependent RNA polymerase via subpocket 2 binding.	Sep/18/2020
Spontaneous binding of potential COVID-19 drugs (Camostat and Nafamostat) to human serine protease TMPRSS2 TMPRSS2 Small molecule In silico	in silico	6.02	Predicted to bind the active site of the TMPRSS2 protease (with more specificity than camostat).	Dec/28/2020
SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies Spike protein RNA Small molecule Peptide In vitro Antibody Mixed substance	Caco-2 cells; Vero cells; Sera of vaccinated individuals; (VSV) SARS-CoV-2 Spike-pseudotyped virus (WT, B.1.1.7, B.1.351, ant P.1 variants)	38.64	Nafamostat displayed in vitro inhibition of SARS-CoV-2 Spike-pseudotyped virus infection for all tested emergent Spike variants (B.1.1.7, B.1.351, and P.1).	Mar/20/2021

AI-suggested references

Link	Publication date
Nafamostat mesylate monotherapy in patients with moderate COVID-19 : A single-center retrospective study.	Feb/11/2022
Structural Basis of SARS-CoV-2- and SARS-CoV-Receptor Binding and Small-Molecule Blockers as Potential Therapeutics.	Jun/25/2020
Identification of potent inhibitors against transmembrane serine protease 2 for developing therapeutics against SARS-CoV-2	Sep/30/2021
Co-Spray Dried Nafamostat Mesylate with Lecithin and Mannitol as Respirable Microparticles for Targeted Pulmonary Delivery: Pharmacokinetics and Lung Distribution in Rats.	Sep/19/2021
Nafamostat mesylate-induced hyperkalemia in critically ill patients with COVID-19: Four case reports.	Nov/06/2020
Broad antiviral and anti-inflammatory efficacy of nafamostat against SARS-CoV-2 and seasonal coronaviruses in primary human bronchiolar epithelia	Jun/30/2021
The TMPRSS2 Inhibitor Nafamostat Reduces SARS-CoV-2 Pulmonary Infection in Mouse Models of COVID-19	Feb/11/2022
On a knife's edge of a COVID-19 pandemic: is containment still possible?	Mar/09/2020
Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: Phase 1b/2a experimental study to investigate safety, Pharmacokinetics and Pharmacodynamics	Apr/28/2020
Inhibition of SARS-CoV-2 entry through the ACE2/TMPRSS2 pathway: a promising approach for uncovering early COVID-19 drug therapies	Jul/21/2020
Treatment effect of nafamostat mesylate in patients with COVID-19 pneumonia: study protocol for a randomized controlled trial.	Nov/23/2021
Virtual Screening on Marine Natural Products for Discovering TMPRSS2 Inhibitors	Oct/12/2021
Effective drugs used to combat SARS-CoV-2 infection and the current status of vaccines.	Jan/28/2021
The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner	Oct/20/2021
Synergistic Block of SARS-CoV-2 Infection by Combined Drug Inhibition of the Host Entry Factors PIKfyve Kinase and TMPRSS2 Protease	Aug/18/2021
Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity	Mar/04/2021
Untapping host-targeting cross-protective efficacy of anticoagulants against SARS-CoV-2	Nov/03/2021
Association between Nafamostat Mesylate and In-Hospital Mortality in Patients with Coronavirus Disease 2019: A Multicenter Observational Study	Jun/09/2021

Clinical trials

ID	Title	Status	Phase	Start date	Completion date
NCT04418128	Clinical Efficacy of Nafamostat Mesylate for COVID-19 Pneumonia	Not yet recruiting	Phase 2\|Phase 3	Jun/10/2020	Apr/30/2021
Alternative id - 2020-04-012 Interventions - Drug: Nafamostat Mesylate Study type - Interventional Study results - No Results Available Locations - Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: None (Open Label)\|Primary Purpose: Treatment Enrollment - 84 Age - 18 Years to 85 Years (Adult, Older Adult) Outcome measures - Proportion of patients with clinical improvement\|Time to clinical improvement (TTCI)\|Clinical status assessed by 7-category ordinal scale\|Change in National Early Warning Score (NEWS)\|Time to National Early Warning Score (NEWS) of ≤ 2 and maintained for 24 hours\|Duration of hospitalization\|Duration of new non-invasive ventilation or high flow oxygen use\|Incidence of new non-invasive ventilation or high flow oxygen use\|Duration of new supplement oxygen use\|Incidence of new supplement oxygen use\|Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use\|Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use\|Mortality at day 28\|Time (days) from treatment initiation to death\|Proportions of patients with a negative nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR\|Viral load change (log10 viral load) of nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR\|Adverse events that occurred during treatment

Export (.csv)