Natural Products-Based Drug Design against SARS-CoV-2 Mpro 3CLpro

International Journal of Molecular Sciences

Joaquín M. Campos¹  Njogu M. Kimani²  Rai C. Silva³  Carlos H. T. P. Silva³  Rosivaldo S. Borges³  Cleydson B. R. Santos³  Humberto F. Freitas⁴  Samuel S. R. Pita⁵ 

[1] Department of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Campus of Cartuja, University of Granada, 18071 Granada, Spain;Department of Physical Sciences, University of Embu, Embu 6-60100, Kenya;Graduate Program on Medicinal Chemistry and Molecular Modeling, Institute of Health Science, Federal University of Pará, Augusto Corrêa 01-Guamá, Belém 66075-110, PA, Brazil;Graduate Program on Pharmacy (PPGFAR-UFBA), Pharmacy College, Federal University of Bahia, Salvador 40170-115, BA, Brazil;Laboratory of Bioinformatics and Molecular Modeling (LaBiMM), Pharmacy College, Federal University of Bahia, Av. Barão de Jeremoabo, 147 Ondina, Salvador 40170-115, BA, Brazil;

关键词: COVID-19;    3CLpro;    natural products;    docking;    molecular dynamics;    druggability;   

DOI  :  10.3390/ijms222111739

来源: DOAJ

【 摘 要 】

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 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.

【 授权许可】

Unknown