Natural Products-Based Drug Design against SARS-CoV-2 Mpro 3CLpro Silva, Rai C. Campos Rosa, Joaquín María COVID-19 3CLpro Natural products Docking Molecular dynamics Molecular dynamics ADMET properties Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has received global attention due to the serious threat it poses to public health. Since the outbreak in December 2019, millions of people have been affected and its rapid global spread has led to an upsurge in the search for treatment. To discover hit compounds that can be used alone or in combination with repositioned drugs, we first analyzed the pharmacokinetic and toxicological properties of natural products from Brazil’s semiarid region. After, we analyzed the site prediction and druggability of the SARS-CoV-2 main protease (Mpro), followed by docking and molecular dynamics simulation. The best SARS-CoV-2 Mpro complexes revealed that other sites were accessed, confirming that our approach could be employed as a suitable starting protocol for ligand prioritization, reinforcing the importance of catalytic cysteine-histidine residues and providing new structural data that could increase the antiviral development mainly against SARSCoV-2. Here, we selected 10 molecules that could be in vitro assayed in response to COVID-19. Two compounds (b01 and b02) suggest a better potential for interaction with SARS-CoV-2 Mpro and could be further studied. 2021-11-05T11:17:26Z 2021-11-05T11:17:26Z 2021 info:eu-repo/semantics/article Silva, R.C.; Freitas, H.F.; Campos, J.M.; Kimani, N.M.; Silva, C.H.T.P.; Borges, R.S.; Pita, S.S.R.; Santos, C.B.R. Natural ProductsBased Drug Design against SARS-CoV-2 Mpro 3CLpro. Int. J. Mol. Sci. 2021, 22, 11739. https:// doi.org/10.3390/ijms222111739 http://hdl.handle.net/10481/71310 10.3390/ijms222111739 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI