Other substances

Amantadine

An anti-influenza drug.

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

Amantadine is a tricyclic amine anti-influenza drug. It displays also antiparkinsonian (through dopaminergic activity) and anti-hyperalgesic (likely through anti-cholinergic activity) properties (NCIt). It was also shown to inhibit cathepsin L activity in cell culture, which might be linked to SARS-CoV-2 infection outcome (Zhao et al., 2021).

Amantadine on DrugBank
Amantadine on PubChem
Amantadine on Wikipedia

Marketed as

AMANTADINE HYDROCHLORIDE; ENDANTADINE; GOCOVRI; OSMOLEX ER; PK-MERZ; SYMADINE; SYMMETREL; VIREGYT; VIROSOL

C1C2CC3CC1CC(C2)(C3)N

Supporting references

Link	Tested on	Impact factor	Notes	Publication date
Amantadine Inhibits SARS-CoV-2 In Vitro Small molecule In vitro	Vero E6 cells; SARS-CoV-2 strain hCoV-19/Italy/INMI1-isl/2020; SARS-CoV-2 strain INMI1	3.82	The drug inhibited SARS-CoV-2 infection in Vero E6 cells with an IC50 of 83 μM or 119 μM (two separate experiments). It did not inhibit Spike-ACE2 binding. Despite a rather low potency, the drug was hypothesized to be applicable for topical use.	Mar/24/2021
Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development Cathepsin L Small molecule Animal model In vitro Mechanism	Huh-7 cells; hACE2-mice; (VSV) SARS-CoV-2 Spike-pseudotyped virus	13.49	Amantadine inhibited SARS-CoV-2 pseudovirus infection without significant cytotoxicity in vitro. It was shown to decrease cathepsin L activity in the treated cells. The drug appears to suppress the infection in a mouse model; although, the measured effect was not statistically significant.	Mar/27/2021

AI-suggested references

Link	Publication date
Are central nervous system drugs displaying anti-inflammatory activity suitable for early treatment of COVID-19?	Nov/10/2021
Targeting COVID-19 in Parkinson's Patients: Drugs Repurposed.	Sep/28/2021
Fluvoxamine and amantadine: central nervous system acting drugs repositioned for COVID-19 as early intervention.	Oct/17/2021
Effect of Pre-exposure Use of Amantadine on COVID-19 Infection: A Hospital-Based Cohort Study in Patients With Parkinson's Disease or Multiple Sclerosis	Oct/07/2021
Chemical Probes for Blocking of Influenza A M2 WT and S31N Channels	Feb/25/2022
Amantadine Treatment for People with COVID-19	Jun/12/2020
Potential for the Repurposing of Adamantane Antivirals for COVID-19	Apr/29/2020
Amantadine disrupts lysosomal gene expression: A hypothesis for COVID19 treatment	Apr/30/2020
Efficacy of Ion-Channel Inhibitors Amantadine, Memantine and Rimantadine for the Treatment of SARS-CoV-2 In Vitro	Mar/17/2021
Docking Prediction of Amantadine in the Receptor Binding Domain of Spike Protein of SARS-CoV-2.	Nov/03/2020
Amantadine-assembled nanostimulator enhances dimeric RBD antigen-elicited cross-neutralization against SARS-CoV-2 strains	Jan/12/2022
Amantadine in the prevention of clinical symptoms caused by SARS-CoV-2	Dec/23/2020
Determination of Ligand Binding Modes in Hydrated Viral Ion Channels to Foster Drug Design and Repositioning	Dec/01/2021
Adamantanes might be protective from COVID-19 in patients with neurological diseases: multiple sclerosis, parkinsonism and cognitive impairment	Oct/12/2021
Prominent Efficacy of Amantadine against Human Borna Disease Virus Infection In Vitro and In Vivo. Comment on Fink et al. Amantadine Inhibits SARS-CoV-2 In Vitro. Viruses 2021, 13, 539	Dec/04/2020
All-cause mortality among patients treated with repurposed antivirals and antibiotics for COVID-19 in Mexico City: A real-world observational study	Jun/24/2021
Anti-Inflammatory Effects of Amantadine and Memantine: Possible Therapeutics for the Treatment of Covid-19?	Nov/09/2020
Amantadine inhibits known and novel ion channels encoded by SARS-CoV-2 in vitro	Dec/01/2021
Observational study of people infected with SARS-Cov-2, treated with amantadine	Oct/10/2020
The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design	Oct/12/2021
Amantadine-Induced Cardiac Arrest in a Patient With COVID-19	Jan/17/2022
Amantadine as a drug to mitigate the effects of COVID-19	Apr/25/2020
Inhibition of SARS CoV Envelope Protein by Flavonoids and Classical Viroporin Inhibitors.	Jul/08/2021

Clinical trials

ID	Title	Status	Phase	Start date	Completion date
NCT04894617	Amantadine for COVID-19	Recruiting	Phase 3	Jun/01/2021	Apr/01/2022
Alternative id - 02032021\|2021-001177-22 Interventions - Drug: Amantadine\|Drug: Lactose monohydrate Study type - Interventional Study results - No Results Available Locations - Copenhagen University Hospital, Hvidovre, Hvidovre, Denmark Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Triple (Participant, Investigator, Outcomes Assessor)\|Primary Purpose: Treatment Enrollment - 226 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Clinical status on day 14\|Mortality\|Mechanical ventilation\|Hospitalization\|Duration of hospitalization\|PCR SARS-CoV-2\|Adverse events\|Severe adverse events
NCT04952519	Efficacy of Amantadine Treatment in COVID-19 Patients	Recruiting	Phase 3	Mar/30/2021	Apr/30/2022
Alternative id - 00980.045\|2021-000981-13 Interventions - Drug: Amantadine Study type - Interventional Study results - No Results Available Locations - Oddział Chorób Płuc i Niewydolności Oddychania z Pododdziałem NWM i Pododdziałem Zaburzeń Oddychania w Czasie Snu, Kujawsko - Pomorskie Centrum Pulmonologii w Bydgoszczy, Bydgoszcz, Poland\|Oddział Pneumonologii Górnośląskie Centrum Medyczne im. prof. Leszka Gieca Śląskiego Uniwersytetu Medycznego w Katowicach, Katowice, Poland Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Triple (Participant, Care Provider, Investigator)\|Primary Purpose: Treatment Enrollment - 500 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Time to recovery
NCT04854759	The Use of Amantadine in the Prevention of Progression and Treatment of COVID-19 Symptoms	Recruiting	Phase 3	Mar/15/2021	May/31/2022
Alternative id - LUB-COV-2021-01 Interventions - Drug: Amantadine Hydrochloride\|Drug: Placebo Study type - Interventional Study results - No Results Available Locations - Regionalny Szpital Specjalistyczny im. dr Władysława Biegańskiego Oddział Neurologii i Neuroimmunologii Klinicznej, Grudziądz, Poland\|Samodzielny Publiczny Zakład Opieki Zdrowotnej w Kalwarii Zebrzydowskiej, Kalwaria Zebrzydowska, Poland\|Oddział Obserwacyjno-Zakaźny SPSz Woj. Im. Jana Bożego Lublin, Lublin, Poland\|Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie, Lublin, Poland\|Klinika Chorób Wewnętrznych Nefrologii i Endokrynologii Klinicznego Szpitala Wojewódzkiego nr 2 im. Św. Jadwigi Królowej, Rzeszów, Poland\|Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Szpital Kliniczny Dzieciątka Jezus, Warszawa, Poland\|Centralny Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji w Warszawie, Warszawa, Poland\|Oddział Kardiologiczny Samodzielny Publiczny Zespół Zakładów Opieki Zdrowotnej w Wyszkowie, Wyszków, Poland Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Double (Participant, Investigator)\|Primary Purpose: Treatment Enrollment - 200 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Development of clinical deterioration\|Clinical deterioration occurs\|General Health Scale (PROMIS® Global Health Scale)\|The neurological assessment\|Time to clinical deterioration\|Survival time

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