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In Vivo ; 34(3 Suppl): 1593-1596, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-536995

ABSTRACT

The Covid-19 pandemic is a world-wide crisis without an effective therapy. While most approaches to therapy are using repurposed drugs that were developed for other diseases, it is thought that targeting the biology of the SARS-CoV-2 virus, which causes Covid-19, can result in an effective therapeutic treatment. The coronavirus RNA cap structure is methylated by two viral methyltransferases that transfer methyl groups from S-adenosylmethionine (SAM). The proper methylation of the virus depends on the level of methionine in the host to form SAM. Herein, we propose to restrict methionine availability by treating the patient with oral recombinant methioninase, aiming to treat Covid-19. By restricting methionine we not only interdict viral replication, which depends on the viral RNA cap methyaltion, but also inhibit the proliferation of the infected cells, which have an increased requirement for methionine. Most importantly, the virally-induced T-cell- and macrophage-mediated cytokine storm, which seems to be a significant cause for Covid-19 deaths, can also be inhibited by restricting methionine, since T-cell and macrophrage activation greatly increases the methionine requirement for these cells. The evidence reviewed here suggests that oral recombinant methioninase could be a promising treatment for coronavirus patients.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Carbon-Sulfur Lyases/therapeutic use , Coronavirus Infections/drug therapy , Methionine/metabolism , Pneumonia, Viral/drug therapy , RNA Caps/drug effects , RNA Processing, Post-Transcriptional/drug effects , RNA, Viral/drug effects , Administration, Oral , Antiviral Agents/administration & dosage , Bacterial Proteins/administration & dosage , Bacterial Proteins/therapeutic use , Betacoronavirus/physiology , COVID-19 , Carbon-Sulfur Lyases/administration & dosage , Clinical Trials as Topic , Coronavirus Infections/complications , Coronavirus Infections/immunology , Cytokine Release Syndrome/prevention & control , Humans , Lymphocyte Activation/drug effects , Macrophage Activation/drug effects , Meta-Analysis as Topic , Methylation/drug effects , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Pseudomonas putida/enzymology , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , S-Adenosylmethionine/metabolism , SARS-CoV-2 , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunology , Virus Replication/drug effects
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