Natural Products-Based Drug Design against SARS-CoV-2 Mpro 3CLpro
| Autor: | Humberto Fonseca de Freitas, Samuel S. R. Pita, Rosivaldo S. Borges, Cleydson B. R. Santos, Njogu M. Kimani, Rai C. Silva, Joaquín M. Campos, Carlos Henrique Tomich de Paula da Silva |
|---|---|
| Přispěvatelé: | [Silva,RC, Silva,CHTP, Santos,CBR] Graduate Program on Medicinal Chemistry and Molecular Modeling, Institute of Health Science, Federal University of Pará, Belém, PA, Brazil. [Silva,RC, Silva,CHTP] Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil. [Freitas,HF] Graduate Program on Pharmacy (PPGFAR-UFBA), Pharmacy College, Federal University of Bahia, Salvador, Brazil. [Freitas,HF, Pita,SR] Laboratory of Bioinformatics and Molecular Modeling (LaBiMM), Pharmacy College, Federal University of Bahia, Salvador, Brazil. [Campos,JM] Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Campus of Cartuja, University of Granada, Granada, Spain. [Campos,JM] Biosanitary Institute of Granada (ibs.GRANADA), University of Granada, Granada, Spain. [Kimani,NM] Department of Physical Sciences, University of Embu, Kenya. [Silva,CHTP] School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil. [Santos,CBR] Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá, Brazil, This work was supported by the Research Dean and Graduate Studies of the Federal University of Pará (PROPESP/UFPA), Brazilian National Council for Scientific and Technological Development (CNPq), Brazilian Coordination for Improvement of Personnel Higher Education (CAPES), and Bahia Research Foundation (FAPESB, grant numbers APP071/2011, JCB-0039/2013, and RED-008/2013). |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Protein Conformation
Computer science natural products Druggability Viral Nonstructural Proteins Ligands Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::Ligands [Medical Subject Headings] Docking Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents [Medical Subject Headings] Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] Simulación del acoplamiento molecular Drug Discovery Chemicals and Drugs::Amino Acids Peptides and Proteins::Amino Acids::Amino Acids Cyclic::Histidine [Medical Subject Headings] Biology (General) Coronavirus 3C Proteases Spectroscopy media_common Natural products Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models Theoretical::Models Molecular::Molecular Dynamics Simulation [Medical Subject Headings] Drug discovery Simulación de dinámica molecular 3CLpro General Medicine Computer Science Applications Molecular Docking Simulation Drug repositioning Chemistry docking Proteasas 3C de coronavirus Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery::Drug Repositioning [Medical Subject Headings] druggability Drug 2019-20 coronavirus outbreak Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery [Medical Subject Headings] Coronavirus disease 2019 (COVID-19) QH301-705.5 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) media_common.quotation_subject Health Care::Environment and Public Health::Public Health::Disease Outbreaks [Medical Subject Headings] Diseño de fármacos Molecular Dynamics Simulation Molecular dynamics Antiviral Agents Catalysis Drug design Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models Theoretical::Models Molecular::Molecular Docking Simulation [Medical Subject Headings] Article Inorganic Chemistry ANÁLISE TOXICOLÓGICA Geographical Locations::Geographic Locations::Americas::South America::Brazil [Medical Subject Headings] Productos biológicos Humans Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery::Drug Design [Medical Subject Headings] Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Viral Proteins::Viral Nonstructural Proteins [Medical Subject Headings] Physical and Theoretical Chemistry Antiviral Ligandos Molecular Biology QD1-999 ADMET properties Biological Products Binding Sites SARS-CoV-2 Organic Chemistry Drug Repositioning COVID-19 Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Molecular Conformation::Protein Conformation [Medical Subject Headings] Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Binding Sites [Medical Subject Headings] Virology Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings] molecular dynamics COVID-19 Drug Treatment Chemicals and Drugs::Complex Mixtures::Biological Products [Medical Subject Headings] Drug Design Descubrimiento de drogas Antivirales |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 11739, p 11739 (2021) International Journal of Molecular Sciences Volume 22 Issue 21 Digibug. Repositorio Institucional de la Universidad de Granada instname Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | 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. Research Dean and Graduate Studies of the Federal University of Pará (PROPESP/UFPA) Brazilian National Council for Scientific and Technological Development (CNPq) Brazilian Coordination for Improvement of Personnel Higher Education (CAPES) Bahia Research Foundation (FAPESB, grant numbers APP071/2011, JCB-0039/2013, and RED-008/2013) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|