In silico and in vitro inhibition of host-based viral entry targets and cytokine storm in COVID-19 by ginsenoside compound K
SARS-CoV-2 is a novel coronavirus that emerged as an epidemic, causing a respiratory disease with multiple severe symptoms and deadly consequences. ACE-2 and TMPRSS2 play crucial and synergistic roles in the membrane fusion and viral entry of SARS-CoV-2 (COVID-19). The spike (S) protein of SARS-CoV-...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023065490 |
| _version_ | 1797669926919471104 |
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| author | Vinothini Boopathi Jinnatun Nahar Mohanapriya Murugesan Sathiyamoorthy Subramaniyam Byoung Man Kong Sung-Keun Choi Chang-Soon Lee Li Ling Dong Uk Yang Deok Chun Yang Ramya Mathiyalagan Se Chan Kang |
| author_facet | Vinothini Boopathi Jinnatun Nahar Mohanapriya Murugesan Sathiyamoorthy Subramaniyam Byoung Man Kong Sung-Keun Choi Chang-Soon Lee Li Ling Dong Uk Yang Deok Chun Yang Ramya Mathiyalagan Se Chan Kang |
| author_sort | Vinothini Boopathi |
| collection | DOAJ |
| description | SARS-CoV-2 is a novel coronavirus that emerged as an epidemic, causing a respiratory disease with multiple severe symptoms and deadly consequences. ACE-2 and TMPRSS2 play crucial and synergistic roles in the membrane fusion and viral entry of SARS-CoV-2 (COVID-19). The spike (S) protein of SARS-CoV-2 binds to the ACE-2 receptor for viral entry, while TMPRSS2 proteolytically cleaves the S protein into S1 and S2 subunits, promoting membrane fusion. Therefore, ACE-2 and TMPRSS2 are potential drug targets for treating COVID-19, and their inhibition is a promising strategy for treatment and prevention. This study proposes that ginsenoside compound K (G-CK), a triterpenoid saponin abundant in Panax Ginseng, a dietary and medicinal herb highly consumed in Korea and China, effectively binds to and inhibits ACE-2 and TMPRSS2 expression. We initially conducted an in-silico evaluation where G-CK showed a high affinity for the binding sites of the two target proteins of SARS-CoV-2. Additionally, we evaluated the stability of G-CK using molecular dynamics (MD) simulations for 100 ns, followed by MM-PBSA calculations. The MD simulations and free energy calculations revealed that G-CK has stable and favorable energies, leading to strong binding with the targets. Furthermore, G-CK suppressed ACE2 and TMPRSS2 mRNA expression in A549, Caco-2, and MCF7 cells at a concentration of 12.5 μg/mL and in LPS-induced RAW 264.7 cells at a concentration of 6.5 μg/mL, without significant cytotoxicity.ACE2 and TMPRSS2 expression were significantly lower in A549 and RAW 264.7 cells following G-CK treatment. These findings suggest that G-CK may evolve as a promising therapeutic against COVID-19. |
| first_indexed | 2024-03-11T20:52:05Z |
| format | Article |
| id | doaj.art-c049dc7b962c4237bb28be25b27d1890 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-11T20:52:05Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-c049dc7b962c4237bb28be25b27d18902023-10-01T05:59:14ZengElsevierHeliyon2405-84402023-09-0199e19341In silico and in vitro inhibition of host-based viral entry targets and cytokine storm in COVID-19 by ginsenoside compound KVinothini Boopathi0Jinnatun Nahar1Mohanapriya Murugesan2Sathiyamoorthy Subramaniyam3Byoung Man Kong4Sung-Keun Choi5Chang-Soon Lee6Li Ling7Dong Uk Yang8Deok Chun Yang9Ramya Mathiyalagan10Se Chan Kang11Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South KoreaGraduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South KoreaGraduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South KoreaResearch and Development Center, Insilicogen Inc., Yongin, Republic of KoreaDepartment of Oriental Medicinal Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South KoreaDaedong Korea Ginseng Co., Ltd, 86, Gunbuk-ro, Gunbuk-myeon, Geumsan-gun, Chungcheongnam-do 32718 Republic of KoreaDaedong Korea Ginseng Co., Ltd, 86, Gunbuk-ro, Gunbuk-myeon, Geumsan-gun, Chungcheongnam-do 32718 Republic of KoreaDepartment of Oriental Medicinal Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South KoreaGraduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South KoreaGraduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea; Department of Oriental Medicinal Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South KoreaGraduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea; Corresponding author.Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea; Department of Oriental Medicinal Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea; Corresponding author. Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, South Korea.SARS-CoV-2 is a novel coronavirus that emerged as an epidemic, causing a respiratory disease with multiple severe symptoms and deadly consequences. ACE-2 and TMPRSS2 play crucial and synergistic roles in the membrane fusion and viral entry of SARS-CoV-2 (COVID-19). The spike (S) protein of SARS-CoV-2 binds to the ACE-2 receptor for viral entry, while TMPRSS2 proteolytically cleaves the S protein into S1 and S2 subunits, promoting membrane fusion. Therefore, ACE-2 and TMPRSS2 are potential drug targets for treating COVID-19, and their inhibition is a promising strategy for treatment and prevention. This study proposes that ginsenoside compound K (G-CK), a triterpenoid saponin abundant in Panax Ginseng, a dietary and medicinal herb highly consumed in Korea and China, effectively binds to and inhibits ACE-2 and TMPRSS2 expression. We initially conducted an in-silico evaluation where G-CK showed a high affinity for the binding sites of the two target proteins of SARS-CoV-2. Additionally, we evaluated the stability of G-CK using molecular dynamics (MD) simulations for 100 ns, followed by MM-PBSA calculations. The MD simulations and free energy calculations revealed that G-CK has stable and favorable energies, leading to strong binding with the targets. Furthermore, G-CK suppressed ACE2 and TMPRSS2 mRNA expression in A549, Caco-2, and MCF7 cells at a concentration of 12.5 μg/mL and in LPS-induced RAW 264.7 cells at a concentration of 6.5 μg/mL, without significant cytotoxicity.ACE2 and TMPRSS2 expression were significantly lower in A549 and RAW 264.7 cells following G-CK treatment. These findings suggest that G-CK may evolve as a promising therapeutic against COVID-19.http://www.sciencedirect.com/science/article/pii/S2405844023065490GinsenosideCompound KACE-2TMPRSS2Molecular dockingMolecular dynamics simulation |
| spellingShingle | Vinothini Boopathi Jinnatun Nahar Mohanapriya Murugesan Sathiyamoorthy Subramaniyam Byoung Man Kong Sung-Keun Choi Chang-Soon Lee Li Ling Dong Uk Yang Deok Chun Yang Ramya Mathiyalagan Se Chan Kang In silico and in vitro inhibition of host-based viral entry targets and cytokine storm in COVID-19 by ginsenoside compound K Heliyon Ginsenoside Compound K ACE-2 TMPRSS2 Molecular docking Molecular dynamics simulation |
| title | In silico and in vitro inhibition of host-based viral entry targets and cytokine storm in COVID-19 by ginsenoside compound K |
| title_full | In silico and in vitro inhibition of host-based viral entry targets and cytokine storm in COVID-19 by ginsenoside compound K |
| title_fullStr | In silico and in vitro inhibition of host-based viral entry targets and cytokine storm in COVID-19 by ginsenoside compound K |
| title_full_unstemmed | In silico and in vitro inhibition of host-based viral entry targets and cytokine storm in COVID-19 by ginsenoside compound K |
| title_short | In silico and in vitro inhibition of host-based viral entry targets and cytokine storm in COVID-19 by ginsenoside compound K |
| title_sort | in silico and in vitro inhibition of host based viral entry targets and cytokine storm in covid 19 by ginsenoside compound k |
| topic | Ginsenoside Compound K ACE-2 TMPRSS2 Molecular docking Molecular dynamics simulation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023065490 |
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