Subject(s)
COVID-19 , Hospital Mortality , Hospitalization , Humans , Retrospective Studies , SARS-CoV-2ABSTRACT
Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.
Subject(s)
COVID-19/immunology , COVID-19/pathology , Cytokine Release Syndrome/pathology , Venous Thrombosis/immunology , Venous Thrombosis/pathology , Blood Coagulation/immunology , Blood Platelets/immunology , Critical Illness/therapy , Cytokine Release Syndrome/immunology , Endothelium, Vascular/pathology , Fibrinolytic Agents/therapeutic use , Humans , Immunity, Innate/immunology , Lung/blood supply , Lung/pathology , Lung/virology , Monocytes/immunology , Neutrophils/immunology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Venous Thrombosis/prevention & controlSubject(s)
COVID-19 , Decision Making , Editorial Policies , Periodicals as Topic , Humans , Manuscripts, Medical as Topic , Peer Review, Research , SARS-CoV-2Subject(s)
Blood Coagulation Disorders/blood , Coronavirus Infections/blood , Pneumonia, Viral/blood , Thrombotic Microangiopathies/blood , Venous Thromboembolism/blood , Anticoagulants/therapeutic use , Betacoronavirus , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/metabolism , COVID-19 , Coronavirus Infections/metabolism , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/metabolism , Endothelium, Vascular/metabolism , Fibrin Fibrinogen Degradation Products/metabolism , Heparin/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lipid Metabolism , Pandemics , Pneumonia, Viral/metabolism , Prothrombin Time , Pulmonary Embolism/blood , Pulmonary Embolism/drug therapy , Pulmonary Embolism/metabolism , SARS-CoV-2 , Thrombocytopenia/blood , Thrombocytopenia/metabolism , Thrombotic Microangiopathies/drug therapy , Thrombotic Microangiopathies/metabolism , Triglycerides/metabolism , Venous Thromboembolism/drug therapy , Venous Thromboembolism/metabolismABSTRACT
INTRODUCTION: No proven drug and no immunisation are yet available for COVID-19 disease. The SARS-CoV-2 main protease (Mpro), a key coronavirus enzyme, which is a potential drug target, has been successfully crystallised. There is evidence suggesting that statins exert anti-viral activity and may block the infectivity of enveloped viruses. The aim of this study was to assess whether statins are potential COVID-19 Mpro inhibitors, using a molecular docking study. MATERIAL AND METHODS: Molecular docking was performed using AutoDock/Vina, a computational docking program. SARS-CoV-2 Mpro was docked with all statins, while antiviral and antiretroviral drugs - favipiravir, nelfinavir, and lopinavir - were used as standards for comparison. RESULTS: The binding energies obtained from the docking of 6LU7 with native ligand favipiravir, nelfinavir, lopinavir, simvastatin, rosuvastatin, pravastatin, pitavastatin, lovastatin, fluvastatin, and atorvastatin were -6.8, -5.8, -7.9, -7.9, -7.0, -7.7, -6.6, -8.2, -7.4, -7.7, and -6.8 kcal/mol, respectively. The number of hydrogen bonds between statins and amino acid residues of Mpro were 7, 4, and 3 for rosuvastatin, pravastatin, and atorvastatin, respectively, while other statins had two hydrogen bonds. CONCLUSIONS: These results indicate, based upon the binding energy of pitavastatin, rosuvastatin, lovastatin, and fluvastatin, that statins could be efficient SARS-CoV-2 Mpro inhibitors. This is supported by the fact that the effects of some statins, especially pitavastatin, have a binding energy that is even greater than that of protease or polymerase inhibitors. However, further research is necessary to investigate their potential use as drugs for COVID-19.