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1.
Biochimie ; 177: 50-52, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-713261

ABSTRACT

Various interferon (IFN)-inducible transmembrane (IFITM) proteins are known to be expressed in human tissues though only IFITM 1-3 are inducible by IFN. Numerous studies have shown that activation of IFITM3 could suppress infection by influenza and coronaviruses such as the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). In view of the potential application of IFITM proteins' induction to target SARS-CoV-2 infection that causes COVID-19, this article layout insights into the known antiviral mechanisms and therapeutic agents related to IFITM. Blocking viral entry through various mechanisms and the potential application of the FDA approved immunosuppressant agent, mycophenolic acid, as inducer of IFITM3 are among those discussed.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Interferons/pharmacology , Membrane Proteins/drug effects , Mycophenolic Acid/pharmacology , Pneumonia, Viral/drug therapy , RNA-Binding Proteins/drug effects , Animals , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/metabolism , Humans , Immunosuppressive Agents/pharmacology , Membrane Proteins/immunology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/metabolism , RNA-Binding Proteins/immunology , SARS-CoV-2
2.
Gastroenterol Hepatol ; 43(8): 457-463, 2020 Oct.
Article in English, Spanish | MEDLINE | ID: covidwho-639589

ABSTRACT

SARS-CoV-2 infection has produced a pandemic with serious consequences for our health care system. Although liver transplant patients represent only a minority of the population, the hepatologists who follow these patients have tried to coordinate efforts to produce a protocol the management of immunosuppression during SARS-CoV-2 infection. Although there are no solid studies to support general recommendations, experiences with other viral infections (hepatitis C, cytomegalovirus) suggest that management of immunosuppression without mycophenolate mofetil or m-Tor inhibitors (drugs that are also associated with leukopenia and lymphopenia) may be beneficial. It is also important to pay attention to possible drug interactions, especially in the case of tacrolimus, with some of the treatments with antiviral effect given in the context of COVID 19 (lopinavir/ritonavir, azithromycin). Finally, the immunosuppressive effect of immunomodulating drugs (tocilizumab and similar) administered to patients with severe lung disease should be taken into account. The mechanisms of action of the different immunosuppressive drugs are reviewed in this article, as well as their potential effect on SARS-CoV-2 infection, and suggests guidelines for the management of immunosuppression.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Immunosuppressive Agents/adverse effects , Liver Transplantation , Pandemics , Pneumonia, Viral/epidemiology , Adaptive Immunity , Antiviral Agents/pharmacology , Betacoronavirus/immunology , Betacoronavirus/physiology , COVID-19 , Calcineurin Inhibitors/adverse effects , Calcineurin Inhibitors/pharmacology , Calcineurin Inhibitors/therapeutic use , Contraindications, Drug , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Disease Susceptibility , Drug Interactions , Everolimus/adverse effects , Everolimus/pharmacology , Everolimus/therapeutic use , Glucocorticoids/adverse effects , Glucocorticoids/pharmacology , Glucocorticoids/therapeutic use , Humans , Immunity, Innate , Immunocompromised Host , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/adverse effects , Mycophenolic Acid/pharmacology , Mycophenolic Acid/therapeutic use , Pneumonia, Viral/immunology , Postoperative Complications/immunology , Postoperative Complications/prevention & control , SARS-CoV-2 , Sirolimus/adverse effects , Sirolimus/pharmacology , Sirolimus/therapeutic use , TOR Serine-Threonine Kinases/antagonists & inhibitors
3.
Microbiol Immunol ; 64(9): 635-639, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-613452

ABSTRACT

In this study, the anti-severe acute respiratory syndrome coronavirus-2 (anti-SARS-CoV-2) activity of mycophenolic acid (MPA) and IMD-0354 was analyzed. These compounds were chosen based on their antiviral activities against other coronaviruses. Because they also inhibit dengue virus (DENV) infection, other anti-DENV compounds/drugs were also assessed. On SARS-CoV-2-infected VeroE6/TMPRSS2 monolayers, both MPA and IMD-0354, but not other anti-DENV compounds/drugs, showed significant anti-SARS-CoV-2 activity. Although MPA reduced the viral RNA level by only approximately 100-fold, its half maximal effective concentration was as low as 0.87 µ m, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets the coronaviral papain-like protease and an in-depth study on its mechanism of action would be useful in the development of novel anti-SARS-CoV-2 drugs.


Subject(s)
Antiviral Agents/pharmacology , Benzamides/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Mycophenolic Acid/pharmacology , Pneumonia, Viral/drug therapy , Animals , COVID-19 , Chlorocebus aethiops , Coronavirus Infections/virology , Dengue Virus/drug effects , Humans , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Vero Cells , Virus Replication/drug effects
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