Adamantanes for the prevention of COVID-19

Dear Editor,

In the midst of the new coronavirus pandemic which originated in Wuhan (China) at the end of 2019, all types of treatment, prevention and patient care strategies for those infected by SARS-CoV-2 have been proposed. People are working incessantly to obtain a drug or combination of drugs which would be capable of defeating the virus and dealing with the infection: hydroxychloroquine, remdesivir, favipravir and merimepodib, lopinavir, ritonavir, dexamethasone anti-inflammatory agents, anticoagulants, astemizole and clofazamine among others. In the very short time since SARS-CoV-2 began many types of drugs have been tried and unfortunately, many of them have been ruled out for their inefficacy against the virus. Furthermore, different vaccines are being developed, now in clinical research phases.

At a virological level, SARS-CoV-2 can cause acute, highly lethal pneumonia (COVID-19) with one of the most common symptoms being difficulty in breathing, sustained fever and fatigue; and the great majority of patients in intensive care units require mechanical ventilation. It has also been reported that SARS-CoV-2 has a neurotropical activity with neurological consequences, leading to breathing difficulties due to the invasion of the virus in the brain stem. The highest mortality rates are among the geriatric population and people with comorbidities and immunological dysfunction.

In the midst of the pandemic, amantadine has recovered particular interest, since several authors suggest the hypothesis that it may be protective against SARS-CoV-2 infection. Amantadine is an inexpensive drug, compared with others. It is an antiviral against influenza type A which inhibits the attachment of viral particles and subsequent release of nucleic acid, preventing the fusion of the viral envelope with the vacuole membrane, which interferes with the penetration of the virus through the cell membrane. It may be used for the treatment of symptoms and as prophylaxis of the flu virus. It is also used in patients with Parkinson’s disease, for the treatment of symptoms such as stiffness, shaking, hypokinesia and akinesia, since it is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist which acts on glutamatergic transmission, correcting the imbalance between glutamatergic and dopaminergic pathways. As such, it improves dopaminergic response of the central nervous system (CNS), releases stored dopamine and norepinyphrine, and prevents re-uptake.

Aranda suggested that amantadine blocks the viroporin channel of COVID-19, preventing the release of the viral nucleus to the cell cytoplasm.¹ Redjak et al.² assessed the severity of COVID-19 in patients with multiple sclerosis, Parkinson’s disease and cognitive impairment, with infection by SARS-CoV-2 confirmed by the polymerase chain reaction (PCR), all of whom received treatment with amantadine or memantine and none of whom developed clinical COVID-19 symptoms. Tipton et al.³ proposed amantadine and memantine as two potential candidates for their cost-effectiveness and low risk. Cimolai⁴ suggests that the laboratories should include adamantanes for assessment against COVID-19. Smieszek et al.⁵ put forward the hypothesis that amantadine could reduce the viral load in patients testing positive for SARS-CoV-2, since it reduces the replication and infectiousness of the virus. Araújo et al.⁶ considered that amantadinae could reduce the effects of COVID-19, including acute respiratory distress syndrome (ARDS), viral replication and ventilator-dependency. Wiwanitkit⁷ affirmed that there are many standard drugs which would be useful for the treatment of COVID-19, among which are amantadinae. Cortés-Borra⁸ commented on a clinical case study of a patient who was taking amantadine to mitigate the effects of Parkinson’s and did not contract the coronavirus disease, despite being in close and continuous contact with her husband, who did contract COVID-19 and died from it.

Support for father research and an exchange of knowledge are therefore needed to provide healthcare systems with useful tools in the prevention and treatment of this serious health crisis. A low risk and affordable strategy would be the re-use of inexpensive and easily available drugs such as the adamantanes. Amantadine may prevent the development of symptoms in people who are asymptomatic and reduce the number of deaths. At this current time of uncertainty when hundreds of deaths are due to infection by COVID-19, alternatives must be found to mitigate the effects of the coronavirus, in the absence of any available vaccine.