TY - JOUR
T1 - Molecular docking and dynamics simulation reveal withanolides as potent antivirals against dengue virus
AU - Lee, Michelle Felicia
AU - Tan, Sang Loon
AU - Ahemad, Nafees
AU - Hamid, Azzmer Azzar Abdul
AU - Hishamuddin, Siti Aishah Sufira Nor
AU - Batumalaie, Kalaivani
AU - Afzal, Sheryar
AU - Wu, Yuan Seng
N1 - Funding Information:
This work was financially supported by the Sunway University research grants, project no. GRTIN-IGS-CVVR[S]-03-2022 and GRTIN-IGS(02)-CVVR-13-2023.
Publisher Copyright:
© 2024 SAAB
PY - 2024/6
Y1 - 2024/6
N2 - The prevalence of dengue remains a significant global threat to public health with millions of infections reported annually due to the lack of effective treatment options. Natural resources such as plants contain phytochemicals with desirable therapeutic effects. For instance, the Indian ginseng, Withania somnifera L. (Solanaceae), contains steroidal lactones, saponins, glycosides, and alkaloids which possessed antiviral activities against various viruses. In this study, docking analysis of seven compounds and phytochemicals were performed against the structural and non-structural (NS) proteins of all four dengue virus (DENV) serotypes as well as host cell receptors such as DC-SIGN and CLEC5A. Withanolide A (L5) was selected as the best inhibitor with high binding affinities towards ten targets consisting of DENV structural and NS proteins as well as the CLEC5A receptor. L5 also showed a fair stability with DENV1, DENV2, and DENV3 over a time span of 100 ns via molecular dynamics simulation. L5 demonstrated good drug-likeness properties, a moderate bioavailability score of 0.55, and is predicted to have high gastrointestinal absorptivity. The data from this in silico study revealed the potential of withanolide A to be further developed as an antiviral against dengue. This is the first study to report the in silico analyses of phytochemicals derived from W. somnifera L. (Solanaceae) against the viral proteins of DENV1 to 4 and their respective host cell receptors.
AB - The prevalence of dengue remains a significant global threat to public health with millions of infections reported annually due to the lack of effective treatment options. Natural resources such as plants contain phytochemicals with desirable therapeutic effects. For instance, the Indian ginseng, Withania somnifera L. (Solanaceae), contains steroidal lactones, saponins, glycosides, and alkaloids which possessed antiviral activities against various viruses. In this study, docking analysis of seven compounds and phytochemicals were performed against the structural and non-structural (NS) proteins of all four dengue virus (DENV) serotypes as well as host cell receptors such as DC-SIGN and CLEC5A. Withanolide A (L5) was selected as the best inhibitor with high binding affinities towards ten targets consisting of DENV structural and NS proteins as well as the CLEC5A receptor. L5 also showed a fair stability with DENV1, DENV2, and DENV3 over a time span of 100 ns via molecular dynamics simulation. L5 demonstrated good drug-likeness properties, a moderate bioavailability score of 0.55, and is predicted to have high gastrointestinal absorptivity. The data from this in silico study revealed the potential of withanolide A to be further developed as an antiviral against dengue. This is the first study to report the in silico analyses of phytochemicals derived from W. somnifera L. (Solanaceae) against the viral proteins of DENV1 to 4 and their respective host cell receptors.
KW - Antiviral
KW - Dengue virus
KW - Flavivirus
KW - Phytochemicals
KW - Withanolides
UR - http://www.scopus.com/inward/record.url?scp=85192101190&partnerID=8YFLogxK
U2 - 10.1016/j.sajb.2024.04.045
DO - 10.1016/j.sajb.2024.04.045
M3 - Article
AN - SCOPUS:85192101190
SN - 0254-6299
VL - 169
SP - 426
EP - 434
JO - South African Journal of Botany
JF - South African Journal of Botany
ER -
