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Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2

Rampogu et al., International Journal of Molecular Sciences, doi:10.3390/ijms23031771
Feb 2022  
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Curcumin for COVID-19
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In Silico molecular dynamics simulation study finding a curcumin analogue (curA) as a promising dual inhibitor for SARS-CoV-2.
In Silico studies predict inhibition of SARS-CoV-2 with curcumin or metabolites via binding to the spike Note A, Nag, Moschovou, Kandeil, Singh (B) (and specifically the receptor binding domain Note B, Kant, Srivastava, Eleraky), Mpro Note C, Moschovou, Kandeil, Srivastava, Naderi Beni, Rajagopal, Rampogu, Sekiou, Singh, Winih Kinasih, Thapa, Bahun, Eleraky, RNA-dependent RNA polymerase Note D, Singh (C), Eleraky, ACE2 Note E, Singh (B), Thapa, Alkafaas, nucleocapsid Note F, Hidayah, Suravajhala, and nsp10 Note G, Suravajhala proteins. In Vitro studies demonstrate inhibition of the spike Note A, Mohd Abd Razak (and specifically the receptor binding domain Note B, Goc (B)), Mpro Note C, Bahun, Guijarro-Real, Mohd Abd Razak, Wu, ACE2 Note E, Goc (B), and TMPRSS2 Note H, Goc (B) proteins. In Vitro studies demonstrate efficacy in Calu-3 Note I, Bormann, A549 Note J, Mohd Abd Razak, 293T Note K, Zhang, HEK293-hACE2 Note L, Nittayananta, Wu, 293T/hACE2/TMPRSS2 Note M, Septisetyani, and Vero E6 Note N, Bormann, Eleraky, Kandeil, Leka, Mohd Abd Razak, Nittayananta, Singh, Teshima, Marín-Palma cells. Curcumin is predicted to inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain and the human ACE2 receptor for the delta and omicron variants Kant, decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells Marín-Palma, and alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress Zhang.
Rampogu et al., 4 Feb 2022, peer-reviewed, 5 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2
Shailima Rampogu, Gihwan Lee, Jun Sung Park, Keun Woo Lee, Myeong Ok Kim
International Journal of Molecular Sciences, doi:10.3390/ijms23031771
Recently, the world has been witnessing a global pandemic with no effective therapeutics yet, while cancer continues to be a major disease claiming many lives. The natural compound curcumin is bestowed with multiple medicinal applications in addition to demonstrating antiviral and anticancer activities. In order to elucidate the impact of curcumin on COVID-19 and cancer, the current investigation has adapted several computational techniques to unfold its possible inhibitory activity. Accordingly, curcumin and similar compounds and analogues were retrieved and assessed for their binding affinities at the binding pocket of SARS-CoV-2 main protease and DDX3. The best binding pose was escalated to molecular dynamics simulation (MDS) studies to assess the time dependent stability. Our findings have rendered one compound that has demonstrated good molecular dock score complemented by key residue interactions and have shown stable MDS results inferred by root mean square deviation (RMSD), radius of gyration (Rg), binding mode, hydrogen bond interactions, and interaction energy. Essential dynamics results have shown that the systemadapts minimum energy conformation to attain a stable state. The discovered compound (curA) could act as plausible inhibitor against SARS-CoV-2 and DDX3. Furthermore, curA could serve as a chemical scaffold for designing and developing new compounds.
Supplementary Materials: The following supporting information can be downloaded at: https: // Conflicts of Interest: The authors declare no conflict of interest.
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