The potential of memantine and related adamantanes such as amantadine, to reduce the neurotoxic effects of COVID‐19, including ARDS and to reduce viral replication through lysosomal effects

Brenner, Steven R.

doi:10.1002/jmv.26030

Cited by 24 publications

(21 citation statements)

References 10 publications

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“…Three of the patients in this series were on amantadine as part of the management of their parkinsonism, and three were on memantine for dementia. There has been an interest in the potential of adamantanes to alter the course of COVID-19 based on their ability to interfere with viroporin protein channels responsible for the release of RNA-viruses from infected cells [ 22 ]. Amantadine in particular was also recently discovered to downregulate the expression CTSL gene coding for the cathepsin L, a lysosomal protease involved in SARS-CoV-2 entry into cells [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics of Coronavirus Disease 2019 (COVID-19) among Patients at a Movement Disorders Center

et al. 2020

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It is not established whether SARS-CoV-2 (COVID-19) patients with movement disorders, are at greater risk for more serious outcomes than the larger COVID-19 population beyond the susceptibility associated with greater age. We reviewed electronic health records and conducted telephone interviews to collect the demographics and clinical outcomes of patients seen at our Movement Disorders Center who tested positive for COVID-19 from 8 March 2020 through 6 June 2020. Thirty-six patients were identified, 23 men and 13 women, median age of 74.5 years. They primarily carried diagnoses of idiopathic Parkinson disease (n = 22; 61%) and atypical parkinsonism (n = 7; 19%) with the balance having other diagnoses. Twenty-seven patients (75%) exhibited alteration in mental status and fifteen (42%) had abnormalities of movement as common manifestations of COVID-19; in 61% and 31%, respectively, these were the presenting symptoms of the disease. Sixty-seven percent of patients in our cohort required hospitalization, and the mortality rate was 36%. These data demonstrate that in patients with movement disorders, the likelihood of hospitalization and death after contracting COVID-19 was greater than in the general population. Patients with movement disorders frequently presented with altered mental status, generalized weakness, or worsening mobility but not anosmia.

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Section: Discussionmentioning

confidence: 99%

Clinical Characteristics of Coronavirus Disease 2019 (COVID-19) among Patients at a Movement Disorders Center

et al. 2020

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“…Podophyllotoxin is highly active against HIV and human papillomavirus (HPV) in vitro (Hensel et al, 2020). Amantadine and acyclovir, as antiviral agents, are also predicted to treat COVID-19, and amantadine has shown therapeutic effects in other studies on COVID-19 treatment (Aranda Abreu et al, 2020;Brenner, 2020;Rejdak and Grieb, 2020). However, the therapeutic effects of candidate drugs identified by Cmap predictions must be further investigated to generate empirical evidence.…”

Section: Discussionmentioning

confidence: 99%

Underlying Mechanisms and Candidate Drugs for COVID-19 Based on the Connectivity Map Database

Yang

2020

Front. Genet.

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Background: The coronavirus disease 2019 (COVID-19) has become a worldwide public health crisis. At present, there are no effective antiviral drugs to treat COVID-19. Although some vaccines have been developed, late-stage clinical trials that allow licensure by regulatory agencies are still needed. Previous reports have indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV are highly homologous and both use angiotensin-converting enzyme 2 (ACE2) as the receptor to enter cells, and SARS-CoV infection reduces the ACE2 expression in the lung. Therefore, the analysis of genes co-expressed with ACE2 in the lung may uncover the underlying mechanism of COVID-19. Finally, we used the Connectivity map (Cmap) database to search for candidate drugs using transcriptome profiles of patients with COVID-19. Method: Based on the differentially expressed genes (DEGs), indicated by the expression of RNAs isolated from bronchoalveolar lavage fluid (BALF) cells of patients with COVID-19, we performed functional enrichment analysis and hub gene cluster analysis. Furthermore, we identified genes co-expressed with ACE2 in healthy lung samples and analyzed the significant genes. Additionally, to identify several candidate drugs for the treatment of COVID-19, we queried Cmap using DEGs and genes co-expressed with ACE2. Results and Conclusion: The up-regulated genes in the BALF cells of patients with COVID-19 are related to viral mRNA translation. The down-regulated genes are related to immune response functions. Genes positively correlated with ACE2 are related to immune defense and those negatively correlated are enriched in synaptic transmission functions. The results reflected prosperous viral proliferation and immune dysfunction in patients. Furthermore, ACE2 may not only mediate viral entrance, but also play an important role in immune defense. By using Cmap with transcriptome profiles of patients with COVID-19, we identified candidate drugs for the treatment of COVID-19, such as amantadine and acyclovir.

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“…We read with interest the papers by Brenner 1 with NMDA activity and inhibits excess glutamate release in the medulla, which is a potential neurotoxic effect resulting from ACE2 depletion and which contributes to the development of acute respiratory distress syndrome via activating the sympathetic nervous system, thereby leading to increased blood pressure, systemic vasoconstriction, and pulmonary capillary leakage. 1,2 Memantine also directly inhibits viral replication through potential interaction with viral E protein and lysosomal function. 3 A recent study reported that 22 patients with the neurologic disorder who were diagnosed with polymerase chain reaction-confirmed SARS-CoV-2 infection and treated with memantine or related adamantanes did not develop clinical symptoms of COVID-19.…”

Section: A Retrospective Review Of Memantine Use and Covid-19-associamentioning

confidence: 99%

A retrospective review of memantine use and COVID‐19‐associated mortality from a national database

Park

Kwon

2020

Journal of Medical Virology

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who are at higher risk of COVID-19, and, therefore, ideal candidates for retrospective investigations aimed at determining whether memantine has therapeutic effects on COVID-19. In conclusion, our analysis revealed no association between memantine treatment and mortality in patients with COVID-19. However, we must explore all feasible options for preventing and treating COVID-19 due to the current lack of licensed vaccines or therapeutics for the disease. A low-risk and cost-effective strategy could be trial repurposing of medications that are inexpensive and readily available. Future studies should analyze whether memantine can shorten the clinical course and/or improve patient outcomes according to disease severity as well as overall mortality of COVID-19.

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The potential of memantine and related adamantanes such as amantadine, to reduce the neurotoxic effects of COVID‐19, including ARDS and to reduce viral replication through lysosomal effects

Cited by 24 publications

References 10 publications

Clinical Characteristics of Coronavirus Disease 2019 (COVID-19) among Patients at a Movement Disorders Center

Clinical Characteristics of Coronavirus Disease 2019 (COVID-19) among Patients at a Movement Disorders Center

Underlying Mechanisms and Candidate Drugs for COVID-19 Based on the Connectivity Map Database

A retrospective review of memantine use and COVID‐19‐associated mortality from a national database

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