Conference abstract
3CL-pro inhibitors from discoglypremna caloneura and Pterocarpus erinaceus and their molecular docking investigation
Pan African Medical Journal - Conference Proceedings. 2023:18(79).03
Oct 2023.
doi: 10.11604/pamj-cp.2023.18.79.2033
Archived on: 03 Oct 2023
Contact the corresponding author
Keywords: NSP5 inhibitors, compounds, molecular docking, baicalin
Poster
3CL-pro inhibitors from discoglypremna caloneura and Pterocarpus erinaceus and their molecular docking investigation
Toukam Djouonzo Paul1,&, Dae-Geun Song2, Nangmo Kemda Pamela1, Sayan Dutta Gupta2, Kopa Kowa Theodora1, Tchinda Tiabou Alembert1, Agbor Agbor Gabriel1
1Institute of Medical Research and Medicinal Plant Studies (IMPM), Douala, Cameroon, 2Korea Institute of Science and Technology (KIST), South Korea
&Corresponding author
Introduction: the COVID-19 pandemic, which has emerged in Wuhan City since March 2019, has already caused more than 6,539,058 deaths (WHO, 12 October 2022). All coronaviruses require the proteolytic activity of the nsp5 protease (3CLpro/Mpro) during virus replication, making it a valuable target for the development of anti-coronavirus therapeutics. The objective was to discover nsp5 inhibitors from Discoglypremna caloneura and Pterocarpus erinaceus.
Methods: compounds were isolated with ordinary column chromatography over silica gel with gradient solvent systems of hexane: ethyl acetate, ethyl acetate: methanol and dichloromethane: methanol. Hemi–synthesis reactions were carried out in a single-step closed system and sometimes with reflux. To identify inhibitors of nsp5, the FRET-based nsp5 activity assay was used to screen isolated and hemi-synthetic compounds as described by Zeng et al. (2021) with slight modification. AutoDock and FlexX were used to evaluate ligand-receptor interactions in molecular docking.
Results: a total of thirteen compounds isolated from D. caloneura and P. erinaceus together with four derivatives were screened. Two derivatized compounds displayed significant improvement in the activity from the starting material, friedelin through the act reduced to the acetoxy product with respective IC50 values of 100, 69, and 41 µM. The latter displayed the highest activity although lower as compared to that of baicalin, the positive control which is 22 µM. The molecular docking was also investigated to abide by the observed in vitro assay. A newly characterized glycerolated ceramide is also reported.
Conclusion: our findings confirm the hypothesis that more potent scaffolds for coronaviruses could be found in our medicinal plants. Plant natural products and molecular docking for the discovery of nsp5 inhibitors are complementary studies whose further exploration is relevant for the prevention and treatment of future emerging and/or re-emerging viral diseases.
3CL-pro inhibitors from discoglypremna caloneura and Pterocarpus erinaceus and their molecular docking investigation
Toukam Djouonzo Paul1,&, Dae-Geun Song2, Nangmo Kemda Pamela1, Sayan Dutta Gupta2, Kopa Kowa Theodora1, Tchinda Tiabou Alembert1, Agbor Agbor Gabriel1
1Institute of Medical Research and Medicinal Plant Studies (IMPM), Douala, Cameroon, 2Korea Institute of Science and Technology (KIST), South Korea
&Corresponding author
Introduction: the COVID-19 pandemic, which has emerged in Wuhan City since March 2019, has already caused more than 6,539,058 deaths (WHO, 12 October 2022). All coronaviruses require the proteolytic activity of the nsp5 protease (3CLpro/Mpro) during virus replication, making it a valuable target for the development of anti-coronavirus therapeutics. The objective was to discover nsp5 inhibitors from Discoglypremna caloneura and Pterocarpus erinaceus.
Methods: compounds were isolated with ordinary column chromatography over silica gel with gradient solvent systems of hexane: ethyl acetate, ethyl acetate: methanol and dichloromethane: methanol. Hemi–synthesis reactions were carried out in a single-step closed system and sometimes with reflux. To identify inhibitors of nsp5, the FRET-based nsp5 activity assay was used to screen isolated and hemi-synthetic compounds as described by Zeng et al. (2021) with slight modification. AutoDock and FlexX were used to evaluate ligand-receptor interactions in molecular docking.
Results: a total of thirteen compounds isolated from D. caloneura and P. erinaceus together with four derivatives were screened. Two derivatized compounds displayed significant improvement in the activity from the starting material, friedelin through the act reduced to the acetoxy product with respective IC50 values of 100, 69, and 41 µM. The latter displayed the highest activity although lower as compared to that of baicalin, the positive control which is 22 µM. The molecular docking was also investigated to abide by the observed in vitro assay. A newly characterized glycerolated ceramide is also reported.
Conclusion: our findings confirm the hypothesis that more potent scaffolds for coronaviruses could be found in our medicinal plants. Plant natural products and molecular docking for the discovery of nsp5 inhibitors are complementary studies whose further exploration is relevant for the prevention and treatment of future emerging and/or re-emerging viral diseases.
