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

Aranda-Abreu, Gonzálo Emiliano; Aranda-Martínez, José Dolores; Araújo, Ramiro; Hernández-Aguilar, María Elena; Herrera-Covarrubias, Deissy; Rojas-Durán, Fausto

doi:10.1007/s43440-020-00168-1

Cited by 36 publications

(29 citation statements)

References 20 publications

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“…Only three observational clinical case reports with small numbers of patients ( n ≤ 15 for all) speculated that amantadine may be used for COVID-19 treatment, no systematic clinical trial in a human population was performed. 47 – 49 Some other papers only raised a hypothesis but without any validation experiment. 50 , 51 In this study, we systematically investigated the role of amantadine in the treatment of COVID-19 and found that amantadine inhibited CTSL enzyme activity in the setting of SARS-CoV-2 pseudovirus infection.…”

Section: Discussionmentioning

confidence: 99%

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

Zhao

Yang

et al. 2021

Sig Transduct Target Ther

401

377

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To discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

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Section: Discussionmentioning

confidence: 99%

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

Zhao

Yang

et al. 2021

Sig Transduct Target Ther

401

377

View full text Add to dashboard Cite

show abstract

“…In 1976, amantadine was developed for the treatment of influenza H1N1; however, this drug is not recommended for the treatment of influenza, because it mutates and loses sensitivity to the drug [ 112 ]. A small observational study of amantadine in COVID-19 gave some promising results [ 112 ]. The potential utility of memantine and other adamantane derivatives in COVID-19 has been recently discussed.…”

Section: The Lessons From the Immunomodulatory Therapy Of Covid-19 Fomentioning

confidence: 99%

Influenza infection, SARS, MERS and COVID-19: Cytokine storm – The common denominator and the lessons to be learned

Ryabkova

Чурилов

Shoenfeld

2021

Clinical Immunology

114

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“…For instance, the drugs amantadine and rimantadine, formerly approved as anti-Influenza A virus agents, have gained attention as possible antiviral agents for other virus-driven infections [ 14 ]. In this respect, an observational study described the amantadine as a possible repurposing drug for patients with Coronavirus disease 2019 (COVID-19) [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Memantine hydrochloride: a drug to be repurposed against Chikungunya virus?

et al. 2021

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Background Chikungunya fever is an endemic disease caused by the Chikungunya virus (CHIKV) to which there is no vaccine or effective antiviral drug treatment so far. Our study aimed to evaluate the potential anti-CHIKV activity of memantine hydrochloride (mtnH), a drug from the class of the aminoadamantanes approved for the treatment of Alzheimer´s disease, as a possible drug to be repurposed to the treatment of Chikungunya fever. Methods MtnH antiviral activity against CHIKV was determined by infecting BHK-21 cells with CHIKV-nanoluc, a virus carrying the marker nanoluciferase reporter, in the presence or absence of mtnH at concentrations ranging from 500 to 1.45 µM. The effective concentration of 50% inhibition (EC 50 ) was calculated. Cell viability assay (determination of CC 50 ) was also performed employing BHK-21 cells. Mutagenic assays were performed by the Salmonella Typhimurium/microsome assay (Ames test). Results MtnH presented a CC 50 of 248.4 ± 31.9 µM and an EC 50 of 32.4 ± 4 µM against CHIKV in vitro. The calculated selectivity index (SI) was 7.67. MtnH did not induce genetic mutation in Salmonella strains with or without an external metabolizing system. Conclusion With the data herein presented, it is possible to hypothesize mtnH as a viable candidate to be repurposed as an anti-CHIKV drug. Clinical assays are, therefore, encouraged due to the promising in vitro results.

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

Cited by 36 publications

References 20 publications

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 plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

Influenza infection, SARS, MERS and COVID-19: Cytokine storm – The common denominator and the lessons to be learned

Memantine hydrochloride: a drug to be repurposed against Chikungunya virus?

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