The acute respiratory syndrome caused by the SARS-CoV-2, known as COVID-19, has been ruthlessly tormenting the world population for more than six months. However, so far no effective drug or vaccine against this plague have emerged yet, despite the huge effort in course by researchers and pharmaceutical companies worldwide. Willing to contribute with this fight to defeat COVID-19, we performed a virtual screening study on a library containing Food and Drug Administration (FDA) approved drugs, in a search for molecules capable of hitting three main molecular targets of SARS-CoV-2 currently available in the Protein Data Bank (PDB). Our results were refined with further molecular dynamics (MD) simulations and MM-PBSA calculations and pointed to 7 multi-target hits which we propose here for experimental evaluation and repurposing as potential drugs against COVID-19. Additional rounds of docking, MD simulations and MM-PBSA calculations with remdesivir suggested that this compound can also work as a multi-target drug against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Coordination of Chemistry Federal Institute of Education Science and Technology of Rio de Janeiro Rio de Janeiro RJ Brazil

Department of Chemical Engineering Instituto Militar de Engenharia Rio de Janeiro RJ Brazil

Department of Chemistry Federal Institute of Espírito Santo Unit Vila Velha Vila Velha ES Brazil

Department of Chemistry Pontifical Catholic University of Rio de Janeiro Rio de Janeiro RJ Brazil

Faculty of Science Department of Chemistry University of Hradec Kralove Hradec Kralove Czech Republic

INRS Centre Armand Frappier Santé Biotechnologie 531 Boulevard des Prairies Laval QC Canada

Institute of Chemical Biological Radiological and Nuclear Defense Rio de Janeiro RJ Brazil

Laboratory of Molecular Modeling Applied to Chemical and Biological Defense Military Institute of Engineering Rio de Janeiro RJ Brazil

PPGQUI Federal University of Espirito Santo Vitoria ES Brazil

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Molecular modeling study of natural products as potential bioactive compounds against SARS-CoV-2

Modeling studies on the role of vitamins B1 (thiamin), B3 (nicotinamide), B6 (pyridoxamine), and caffeine as potential leads for the drug design against COVID-19