The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship
The main protease (M<sup>pro</sup>) is a major protease having an important role in viral replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that caused the pandemic of 2020. Here, active M<sup>pro</sup> was obtained as a 34...
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doaj-3728e3ba5fd64f0ea1d2bb46397542dc2021-03-30T23:00:05ZengMDPI AGMolecules1420-30492021-03-01261924192410.3390/molecules26071924The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity RelationshipThi Thanh Hanh Nguyen0Jong-Hyun Jung1Min-Kyu Kim2Sangyong Lim3Jae-Myoung Choi4Byoungsang Chung5Do-Won Kim6Doman Kim7Institutes of Green Bioscience and Technology, Seoul National University, Pyeongchang-gun 25354, Gang-won-do, KoreaRadiation Research Division, Korea Atomic Engery Research Institute, Jeongeup 56212, Jeollabuk-do, KoreaRadiation Research Division, Korea Atomic Engery Research Institute, Jeongeup 56212, Jeollabuk-do, KoreaRadiation Research Division, Korea Atomic Engery Research Institute, Jeongeup 56212, Jeollabuk-do, KoreaOttogi Sesame Mills Co., Ltd., Eumseong-gun 27623, Chungcheongbuk-do, KoreaOttogi Sesame Mills Co., Ltd., Eumseong-gun 27623, Chungcheongbuk-do, KoreaDepartment of Physics, Gangneung-Wonju National University, Gangneung 25457, Gangwon-do, KoreaInstitutes of Green Bioscience and Technology, Seoul National University, Pyeongchang-gun 25354, Gang-won-do, KoreaThe main protease (M<sup>pro</sup>) is a major protease having an important role in viral replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that caused the pandemic of 2020. Here, active M<sup>pro</sup> was obtained as a 34.5 kDa protein by overexpression in <i>E. coli</i> BL21 (DE3). The optimal pH and temperature of M<sup>pro</sup> were 7.5 and 37 °C, respectively. M<sup>pro</sup> displayed a <i>K<sub>m</sub></i> value of 16 μM with Dabcyl-KTSAVLQ↓SGFRKME-Edans. Black garlic extract and 49 polyphenols were studied for their inhibitory effects on purified M<sup>pro</sup>. The IC<sub>50</sub> values were 137 μg/mL for black garlic extract and 9–197 μM for 15 polyphenols. The mixtures of tannic acid with puerarin, daidzein, and/or myricetin enhanced the inhibitory effects on M<sup>pro</sup>. The structure–activity relationship of these polyphenols revealed that the hydroxyl group in C3′, C4′, C5′ in the B-ring, C3 in the C-ring, C7 in A-ring, the double bond between C2 and C3 in the C-ring, and glycosylation at C8 in the A-ring contributed to inhibitory effects of flavonoids on M<sup>pro</sup>.https://www.mdpi.com/1420-3049/26/7/1924main proteaseSARS-CoV-2polyphenolkineticstructure–activity relationshipblack garlic |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Thi Thanh Hanh Nguyen Jong-Hyun Jung Min-Kyu Kim Sangyong Lim Jae-Myoung Choi Byoungsang Chung Do-Won Kim Doman Kim |
spellingShingle |
Thi Thanh Hanh Nguyen Jong-Hyun Jung Min-Kyu Kim Sangyong Lim Jae-Myoung Choi Byoungsang Chung Do-Won Kim Doman Kim The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship Molecules main protease SARS-CoV-2 polyphenol kinetic structure–activity relationship black garlic |
author_facet |
Thi Thanh Hanh Nguyen Jong-Hyun Jung Min-Kyu Kim Sangyong Lim Jae-Myoung Choi Byoungsang Chung Do-Won Kim Doman Kim |
author_sort |
Thi Thanh Hanh Nguyen |
title |
The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship |
title_short |
The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship |
title_full |
The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship |
title_fullStr |
The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship |
title_full_unstemmed |
The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship |
title_sort |
inhibitory effects of plant derivate polyphenols on the main protease of sars coronavirus 2 and their structure–activity relationship |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2021-03-01 |
description |
The main protease (M<sup>pro</sup>) is a major protease having an important role in viral replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that caused the pandemic of 2020. Here, active M<sup>pro</sup> was obtained as a 34.5 kDa protein by overexpression in <i>E. coli</i> BL21 (DE3). The optimal pH and temperature of M<sup>pro</sup> were 7.5 and 37 °C, respectively. M<sup>pro</sup> displayed a <i>K<sub>m</sub></i> value of 16 μM with Dabcyl-KTSAVLQ↓SGFRKME-Edans. Black garlic extract and 49 polyphenols were studied for their inhibitory effects on purified M<sup>pro</sup>. The IC<sub>50</sub> values were 137 μg/mL for black garlic extract and 9–197 μM for 15 polyphenols. The mixtures of tannic acid with puerarin, daidzein, and/or myricetin enhanced the inhibitory effects on M<sup>pro</sup>. The structure–activity relationship of these polyphenols revealed that the hydroxyl group in C3′, C4′, C5′ in the B-ring, C3 in the C-ring, C7 in A-ring, the double bond between C2 and C3 in the C-ring, and glycosylation at C8 in the A-ring contributed to inhibitory effects of flavonoids on M<sup>pro</sup>. |
topic |
main protease SARS-CoV-2 polyphenol kinetic structure–activity relationship black garlic |
url |
https://www.mdpi.com/1420-3049/26/7/1924 |
work_keys_str_mv |
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