Antiviral activity of amiodarone in SARS-CoV-2 disease.

Amiodarone seems to exhibit some antiviral activity in the disease caused by SARS-CoV-2. Here we have examined the SARS-CoV-2 disease course in the entire population of the Czech Republic and compared it with the course of the disease in patients treated with amiodarone in two major Prague's hospitals. In the whole population of the Czech Republic SARS-CoV-2 infected 1665070 persons (15.6 %) out of 10694000 (100 %) between 1 April 2020 and 30 June 2021. In the same time period only 35 patients (3.4 %) treated with amiodarone were infected with SARS-CoV-2 virus out of 1032 patients (100 %) who received amiodarone. It appears that amiodarone can prevent SARS-CoV-2 virus infection by multiple mechanisms. In in-vitro experiments it exhibits SARS-CoV-2 virus replication inhibitions. Due to its anti-inflammatory and antioxidant properties, it may have beneficial effect on the complications caused by SARS-CoV-2 as well. Additionally, inorganic iodine released from amiodarone can be converted to hypoiodite (IO-), which has antiviral and antibacterial activity, and thus can affect the life cycle of the virus.

[1]  Ľ. Stárka,et al.  Androgens in SARS-CoV-2 Coronavirus Infections , 2021, Physiological Research.

[2]  T. Links,et al.  Use of Salivary Iodine Concentrations to Estimate the Iodine Status of Adults in Clinical Practice , 2021, The Journal of nutrition.

[3]  Li Yang,et al.  Identification of SARS-CoV-2 entry inhibitors among already approved drugs , 2020, Acta Pharmacologica Sinica.

[4]  Daniel P. Morin,et al.  Amiodarone in the COVID-19 Era: Treatment for Symptomatic Patients Only, or Drug to Prevent Infection? , 2020, American Journal of Cardiovascular Drugs.

[5]  P. Gurbel,et al.  Ion channel inhibition against COVID-19: A novel target for clinical investigation. , 2020, Cardiology journal.

[6]  G. Lippi,et al.  COVID-19: unravelling the clinical progression of nature’s virtually perfect biological weapon , 2020, Annals of translational medicine.

[7]  Michele Emdin,et al.  Safety and Efficacy of Amiodarone in a Patient With COVID-19 , 2020, JACC: Case Reports.

[8]  Michele Emdin,et al.  Amiodarone as a possible therapy for coronavirus infection , 2020, European journal of preventive cardiology.

[9]  Susan Daniel,et al.  Coronavirus membrane fusion mechanism offers a potential target for antiviral development , 2020, Antiviral Research.

[10]  Linqi Zhang,et al.  Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor , 2020, Nature.

[11]  T. Efferth,et al.  Identification of novel compounds against three targets of SARS CoV-2 coronavirus by combined virtual screening and supervised machine learning , 2020, Computers in Biology and Medicine.

[12]  K. Shi,et al.  Structural basis of receptor recognition by SARS-CoV-2 , 2020, Nature.

[13]  Mandeep R. Mehra,et al.  COVID-19 illness in native and immunosuppressed states: A clinical–therapeutic staging proposal , 2020, The Journal of Heart and Lung Transplantation.

[14]  D. Raoult,et al.  Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial , 2020, International Journal of Antimicrobial Agents.

[15]  G. Herrler,et al.  SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor , 2020, Cell.

[16]  P. Santisteban,et al.  Role of iodide metabolism in physiology and cancer. , 2018, Endocrine-related cancer.

[17]  J. Freed,et al.  The SARS-CoV Fusion Peptide Forms an Extended Bipartite Fusion Platform that Perturbs Membrane Order in a Calcium-Dependent Manner , 2017, Journal of Molecular Biology.

[18]  C. Salata,et al.  Antiviral activity of cationic amphiphilic drugs , 2017, Expert review of anti-infective therapy.

[19]  C. Mammucari,et al.  Calcium at the Center of Cell Signaling: Interplay between Endoplasmic Reticulum, Mitochondria, and Lysosomes. , 2016, Trends in biochemical sciences.

[20]  Peter B. Madrid,et al.  Evaluation of Ebola Virus Inhibitors for Drug Repurposing. , 2015, ACS infectious diseases.

[21]  F. Fabris,et al.  Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process , 2015, Pathogens and disease.

[22]  P. Kopp,et al.  Iodide transport: implications for health and disease , 2014, International Journal of Pediatric Endocrinology.

[23]  M. Manns,et al.  The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry , 2014, The Journal of antimicrobial chemotherapy.

[24]  L. Braverman,et al.  Consequences of excess iodine , 2014, Nature Reviews Endocrinology.

[25]  Y. Bayir,et al.  The protective effect of amiodarone in lung tissue of cecal ligation and puncture-induced septic rats: a perspective from inflammatory cytokine release and oxidative stress , 2013, Naunyn-Schmiedeberg's Archives of Pharmacology.

[26]  D. Dobrev,et al.  Pleiotropic actions of amiodarone: still puzzling after half a century , 2013, Naunyn-Schmiedeberg's Archives of Pharmacology.

[27]  C. Weber,et al.  Presence of luminal neutrophil extracellular traps in atherosclerosis , 2012, Thrombosis and Haemostasis.

[28]  Ari Helenius,et al.  Endosome maturation , 2011, The EMBO journal.

[29]  S. K. Narayana,et al.  Management of amiodarone-related thyroid problems , 2011, Therapeutic advances in endocrinology and metabolism.

[30]  H. Nakaya Does anti-inflammatory action of amiodarone explain the high efficacy in patients with heart failure? , 2009, Circulation journal : official journal of the Japanese Circulation Society.

[31]  Marco Schiavon,et al.  Amiodarone alters late endosomes and inhibits SARS coronavirus infection at a post-endosomal level. , 2008, American journal of respiratory cell and molecular biology.

[32]  S. Inoue,et al.  Clathrin-Dependent Entry of Severe Acute Respiratory Syndrome Coronavirus into Target Cells Expressing ACE2 with the Cytoplasmic Tail Deleted , 2007, Journal of Virology.

[33]  D. Bruttomesso,et al.  Effects of metabolites and analogs of amiodarone on alveolar macrophages: structure-activity relationship. , 2004, American journal of physiology. Lung cellular and molecular physiology.

[34]  G. Naccarelli,et al.  Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation: comparative efficacy and results of trials. , 2003, The American journal of cardiology.

[35]  L. Braverman,et al.  The effects of amiodarone on the thyroid. , 2001, Endocrine reviews.

[36]  T. Bouillon,et al.  Population pharmacokinetics of long‐term oral amiodarone therapy , 2000, Clinical pharmacology and therapeutics.

[37]  A. Weetman,et al.  Amiodarone and the thyroid: a practical guide to the management of thyroid dysfunction induced by amiodarone therapy , 1998, Heart.

[38]  A. Matsumori,et al.  Amiodarone inhibits production of tumor necrosis factor-alpha by human mononuclear cells: a possible mechanism for its effect in heart failure. , 1997, Circulation.