TY - JOUR
T1 - In silico evaluation of flavonoids as potential inhibitors of SARS-CoV-2 main nonstructural proteins (Nsps)—amentoflavone as a multitarget candidate
AU - Portilla-Martínez, Andrés
AU - Ortiz-Flores, Miguel
AU - Hidalgo, Isabel
AU - Gonzalez-Ruiz, Cristian
AU - Meaney, Eduardo
AU - Ceballos, Guillermo
AU - Nájera, Nayelli
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2022/12
Y1 - 2022/12
N2 - Despite the development of vaccines against COVID-19 disease and the multiple efforts to find efficient drugs as treatment for this virus, there are too many social, political, economic, and health inconveniences to incorporate a fully accessible plan of prevention and therapy against SARS-CoV-2. In this sense, it is necessary to find nutraceutical/pharmaceutical drugs as possible COVID-19 preventives/treatments. Based on their beneficial effects, flavonoids are one of the most promising compounds. Therefore, using virtual screening, 478 flavonoids obtained from the KEGG database were evaluated against non-structural proteins Nsp1, Nsp3, Nsp5, Nsp12, and Nsp15, which are essential for the virus-host cell infection, searching for possible multitarget flavonoids. Amentoflavone, a biflavonoid found mainly in Ginkgo biloba, Lobelia chinensis, and Byrsonima intermedia, can interact and bind with the five proteins, suggesting its potential as a multitarget inhibitor. Molecular docking calculations and structural analysis (RMSD, number of H bonds, and clustering) performed from molecular dynamics simulations of the amentoflavone-protein complex support this potential. The results shown here are theoretical evidence of the probable multitarget inhibition of non-structural proteins of SARS-CoV-2 by amentoflavone, which has wide availability, low cost, no side effects, and long history of use. These results are solid evidence for future in vitro and in vivo experiments aiming to validate amentoflavone as an inhibitor of the Nsp1, 3, 5, 12, and 15 of SARS-CoV-2. Graphical Abstract: [Figure not available: see fulltext.]
AB - Despite the development of vaccines against COVID-19 disease and the multiple efforts to find efficient drugs as treatment for this virus, there are too many social, political, economic, and health inconveniences to incorporate a fully accessible plan of prevention and therapy against SARS-CoV-2. In this sense, it is necessary to find nutraceutical/pharmaceutical drugs as possible COVID-19 preventives/treatments. Based on their beneficial effects, flavonoids are one of the most promising compounds. Therefore, using virtual screening, 478 flavonoids obtained from the KEGG database were evaluated against non-structural proteins Nsp1, Nsp3, Nsp5, Nsp12, and Nsp15, which are essential for the virus-host cell infection, searching for possible multitarget flavonoids. Amentoflavone, a biflavonoid found mainly in Ginkgo biloba, Lobelia chinensis, and Byrsonima intermedia, can interact and bind with the five proteins, suggesting its potential as a multitarget inhibitor. Molecular docking calculations and structural analysis (RMSD, number of H bonds, and clustering) performed from molecular dynamics simulations of the amentoflavone-protein complex support this potential. The results shown here are theoretical evidence of the probable multitarget inhibition of non-structural proteins of SARS-CoV-2 by amentoflavone, which has wide availability, low cost, no side effects, and long history of use. These results are solid evidence for future in vitro and in vivo experiments aiming to validate amentoflavone as an inhibitor of the Nsp1, 3, 5, 12, and 15 of SARS-CoV-2. Graphical Abstract: [Figure not available: see fulltext.]
KW - Amentoflavone
KW - Docking
KW - Molecular dynamics
KW - Multitarget
KW - Non-structural protein
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85142938184&partnerID=8YFLogxK
U2 - 10.1007/s00894-022-05391-6
DO - 10.1007/s00894-022-05391-6
M3 - Artículo
C2 - 36445575
AN - SCOPUS:85142938184
SN - 1610-2940
VL - 28
JO - Journal of Molecular Modeling
JF - Journal of Molecular Modeling
IS - 12
M1 - 404
ER -