Silva, Rai C.Freitas, Humberto F.Campos, Joaquín M.Kimani, Njogu M.Silva, Carlos H. T. P.Borges, Rosivaldo S.Pita, Samuel S. R.Santos, Cleydson B. R.2023-01-102023-01-102021-10-29Silva RC, Freitas HF, Campos JM, Kimani NM, Silva CHTP, Borges RS, et al. Natural Products-Based Drug Design against SARS-CoV-2 Mpro 3CLpro. Int J Mol Sci. 2021 Oct 29;22(21):117391661-6596http://hdl.handle.net/10668/4554Coronavirus 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 SARS-CoV-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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/COVID-193CLproNatural productsDockingMolecular dynamicsDruggabilityADMET propertiesAntiviralLigandsDrug discoveryDrug designProteasas 3C de coronavirusProductos biológicosSimulación del acoplamiento molecularSimulación de dinámica molecularAntiviralesLigandosDescubrimiento de drogasDiseño de fármacosMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral AgentsMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Binding SitesMedical Subject Headings::Chemicals and Drugs::Complex Mixtures::Biological ProductsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug DiscoveryMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery::Drug RepositioningMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Molecular::Molecular Docking SimulationMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Molecular::Molecular Dynamics SimulationMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Molecular Conformation::Protein ConformationMedical Subject Headings::Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus InfectionsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Viral Proteins::Viral Nonstructural ProteinsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery::Drug DesignMedical Subject Headings::Geographical Locations::Geographic Locations::Americas::South America::BrazilMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::HistidineMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::LigandsMedical Subject Headings::Health Care::Environment and Public Health::Public Health::Disease Outbreaksresearch article34769170Acceso abierto10.3390/ijms2221117391422-0067PMC8583940