eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2020-06-25 13 2 933 941 10.13005/bpj/1962 33851 article Neyder Contreras-Puentes 1 Antistio Alvíz-Amador 2 GINUMED, Faculty of Medicine, Rafael Nuñez Universitary Corporation, Cartagena D.T y C, Colombia Pharmacology and Therapeutic Group, University of Cartagena, Cartagena D.T y C., Colombia Aims: COVID-19 is a global pandemic that has affected around 186 countries in the world, related to clinical signs as fever, cough and pneumonia. The disease is caused by SARS-CoV-2, in the pathophysiology of SARS-CoV-2 it presents the importance of different structural and functional proteins. Some of these mechanisms are based on proteases such as 3CL-PRO and PL-PRO related to the specific cleavage of polypeptides to replication. Materials and Methods: In order to search for alternatives to counteract the virus, computational screening tools have been used, employing molecular docking methodologies through natural ligands, drugs and analogues against SARS-CoV-2 proteases. Subsequently, were tested by ligand-protein interaction employed AutoDock-Vina and PyRx 0.8. Results: From 93 molecules (38 drugs and analogues with antiviral activity and 55 of natural origin with protease inhibitory activity) selected, the ligands with highest affinity indicated to saikosaponin D and SCHEMBL3057328 for 3CL-PRO; Conversely, for PL-PRO were indicated amentoflavone and MK-3207. The presence of potential inhibitors was contrasted with data from previous studies, in which its capacity in vitro and in vivo was determined to inhibit the development of coronavirus. Thus, substantial contributions in silico in the search for promising alternatives of nature and antiviral drugs, which contributes to the validation and establishment of possible candidates for the inhibition of SARS-CoV-2 proteins, favoring the study of new lines of treatments. https://biomedpharmajournal.org/vol13no2/virtual-screening-of-natural-metabolites-and-antiviral-drugs-with-potential-inhibitory-activity-against-3cl-pro-and-pl-pro/ COVID-19 Drugs Molecular Docking Natural Metabolites SARS-CoV-2