In silico evidence of Remdesivir action in blood coagulation cascade modulation in COVID-19 treatment  

作　　者：Luis Gustavo Pagliarin Lucca Miketen de Oliveira Valentina Nunes Fontoura dos Anjos Cristiano de Bem Torquato de Souza Gabrielle Caroline Peiter Cinthia Façanha Wendel Anderson Dillmann Groto Fabrício Freire de Melo Kádima Nayara Teixeira 

机构地区：[1]Campus Toledo,Universidade Federal do Paraná,Toledo 85.919-899,Paraná,Brazil [2]Programa Multicêntrico de Pós-graduação em Bioquímica e Biologia Molecular-Setor Palotina,Universidade Federal do Paraná,Palotina 85.950-000,Paraná,Brazil [3]Instituto Multidisciplinar em Saúde-Campus Anísio Teixeira,Universidade Federal da Bahia,Vitória da Conquista 45.029-094,Bahia,Brazil

出　　处：《World Journal of Biological Chemistry》2023年第4期72-83,共12页世界生物化学杂志（英文版）（电子版）

摘　　要：BACKGROUND Coronavirus disease 2019(COVID-19)has demonstrated several clinical manifestations which include not only respiratory system issues but also liver,kidney,and other organ injuries.One of these abnormalities is coagulopathies,including thrombosis and disseminated intravascular coagulation.Because of this,the administration of low molecular weight heparin is required for patients that need to be hospitalized.In addition,Remdesivir is an antiviral that was used against Middle East Acute Respiratory Syndrome,Ebola,Acute Respiratory Syndrome,and other diseases,showing satisfactory results on recovery.Besides,there is evidence suggesting that this medication can provide a better prognosis for patients with COVID-19.AIM To investigate in silico the interaction between Remdesivir and clotting factors,pursuing a possibility of using it as medicine.METHODS In this in silico study,the 3D structures of angiotensin-converting enzyme 2(ACE2),Factor I(fibrinogen),Factor II(prothrombin),Factor III(thromboplastin),Factor V(proaccelerin),Factor VII(proconvertin),Factor VIII(antihemophilic factor A),Factor IX(antihemophilic factor B),Factor X(Stuart-Prower factor),and Factor XI(precursor of thromboplastin(these structures are technically called receptors)were selected from the Protein Data Bank.The structures of the antivirals Remdesivir and Osetalmivir(these structures are called ligands)were selected from the PubChem database,while the structure of Atazanavir was selected from the ZINC database.The software AutoDock Tools(ADT)was used to prepare the receptors for molecular docking.Ions,peptides,water molecules,and other ones were removed from each ligand,and then,hydrogen atoms were added to the structures.The grid box was delimited and calculated using the same software ADT.A physiological environment with pH 7.4 is needed to make the ligands interact with the receptors,and still the software Marvin sketch®(ChemAxon®)was used to forecast the protonation state.To perform molecular docking,ADT and Vina software was con

关 键 词：Clotting factors Coagulating blood cascade COVID-19 treatment Remdesivir SARS-CoV-2 

分 类 号：R563.1[医药卫生—呼吸系统]