Amantadine as a drug to mitigate the effects of COVID-19

Aranda-Abreu, Gonzálo Emiliano; Aguilar, María Elena Hernández; Herrera-Covarrubias, Deissy; Rojas-Durán, Fausto

doi:10.1016/j.mehy.2020.109755

Cited by 55 publications

(33 citation statements)

References 10 publications

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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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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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“…Adamantanes (i.e. amantadine, rimantadine) are thought to disrupt lysosomal trafficking, thereby impeding the release of SARS-CoV-2 ribonucleic acid (RNA) into the cell (Araújo et al, 2020[ 2 ]), and by inhibiting conductance of the envelope (E) protein (Aranda Abreu et al, 2020[ 1 ]). Acyclovir, a nucleotide analog antiviral, was found as a candidate drug for COVID-19 by potentially counteracting gene expression changes observed after SARS-CoV-2 infection (Li and Yang, 2020[ 16 ]).…”

Section: Introductionmentioning

confidence: 99%

All-cause mortality among patients treated with repurposed antivirals and antibiotics for COVID-19 in Mexico City: A real-world observational study

Mancilla-Galindo

García-Méndez

Márquez-Sánchez

et al. 2021

EXCLI Journal; 20:Doc199; ISSN 1611-2156

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“…Molecular docking studies have shown that amantadine could enter the SARS-Cov-2 E-channel and interfere with the release of its viral content into the cell, thus inhibiting its propagation [ 12 ]. Other studies have shown that amantadine as a treatment for COVID-19 infection has been effective, and the patients have recovered successfully, without the necessity to go to a hospital [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Observational study of people infected with SARS-Cov-2, treated with amantadine

Aranda-Abreu

Aranda-Martínez²,

Araújo³

et al. 2020

Pharmacol. Rep

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Background We conducted an observational study of 15 patients from a Southeastern area of Mexico with symptoms compatible with SARS-Cov-2, which were treated with the antiviral amantadine. Methodology In this study, data were collected from 15 individuals with clinical symptoms of COVID-19 infection, which were treated on an ambulatory basis with 100 mg of amantadine for a period of 14 days. Results This drug demonstrated its effectiveness, as patients recovered successfully with this treatment without the necessity of attending a hospital to use mechanical ventilation. All patients developed IgG antibodies to SARS-Cov-2. Conclusion Amantadine can be used as a viable and cost-effective alternative for treating people with severe acute respiratory syndrome (SARS-Cov-2) on an ambulatory basis, while the vaccine is not available.

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Amantadine as a drug to mitigate the effects of COVID-19

Cited by 55 publications

References 10 publications

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

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

All-cause mortality among patients treated with repurposed antivirals and antibiotics for COVID-19 in Mexico City: A real-world observational study

Observational study of people infected with SARS-Cov-2, treated with amantadine

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