Cargando…

The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship

The main protease (M(pro)) 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(pro) was obtained as a 34.5 kDa protein by overexpression in E. col...

Descripción completa

Detalles Bibliográficos
Autores principales: Nguyen, Thi Thanh Hanh, Jung, Jong-Hyun, Kim, Min-Kyu, Lim, Sangyong, Choi, Jae-Myoung, Chung, Byoungsang, Kim, Do-Won, Kim, Doman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036510/
https://www.ncbi.nlm.nih.gov/pubmed/33808054
http://dx.doi.org/10.3390/molecules26071924
_version_ 1783676926990221312
author Nguyen, Thi Thanh Hanh
Jung, Jong-Hyun
Kim, Min-Kyu
Lim, Sangyong
Choi, Jae-Myoung
Chung, Byoungsang
Kim, Do-Won
Kim, Doman
author_facet Nguyen, Thi Thanh Hanh
Jung, Jong-Hyun
Kim, Min-Kyu
Lim, Sangyong
Choi, Jae-Myoung
Chung, Byoungsang
Kim, Do-Won
Kim, Doman
author_sort Nguyen, Thi Thanh Hanh
collection PubMed
description The main protease (M(pro)) 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(pro) was obtained as a 34.5 kDa protein by overexpression in E. coli BL21 (DE3). The optimal pH and temperature of M(pro) were 7.5 and 37 °C, respectively. M(pro) displayed a K(m) value of 16 μM with Dabcyl-KTSAVLQ↓SGFRKME-Edans. Black garlic extract and 49 polyphenols were studied for their inhibitory effects on purified M(pro). The IC(50) 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(pro). 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(pro).
format Online
Article
Text
id pubmed-8036510
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80365102021-04-12 The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship Nguyen, Thi Thanh Hanh Jung, Jong-Hyun Kim, Min-Kyu Lim, Sangyong Choi, Jae-Myoung Chung, Byoungsang Kim, Do-Won Kim, Doman Molecules Article The main protease (M(pro)) 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(pro) was obtained as a 34.5 kDa protein by overexpression in E. coli BL21 (DE3). The optimal pH and temperature of M(pro) were 7.5 and 37 °C, respectively. M(pro) displayed a K(m) value of 16 μM with Dabcyl-KTSAVLQ↓SGFRKME-Edans. Black garlic extract and 49 polyphenols were studied for their inhibitory effects on purified M(pro). The IC(50) 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(pro). 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(pro). MDPI 2021-03-30 /pmc/articles/PMC8036510/ /pubmed/33808054 http://dx.doi.org/10.3390/molecules26071924 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Nguyen, Thi Thanh Hanh
Jung, Jong-Hyun
Kim, Min-Kyu
Lim, Sangyong
Choi, Jae-Myoung
Chung, Byoungsang
Kim, Do-Won
Kim, Doman
The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036510/
https://www.ncbi.nlm.nih.gov/pubmed/33808054
http://dx.doi.org/10.3390/molecules26071924
work_keys_str_mv AT nguyenthithanhhanh theinhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT jungjonghyun theinhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT kimminkyu theinhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT limsangyong theinhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT choijaemyoung theinhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT chungbyoungsang theinhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT kimdowon theinhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT kimdoman theinhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT nguyenthithanhhanh inhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT jungjonghyun inhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT kimminkyu inhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT limsangyong inhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT choijaemyoung inhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT chungbyoungsang inhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT kimdowon inhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship
AT kimdoman inhibitoryeffectsofplantderivatepolyphenolsonthemainproteaseofsarscoronavirus2andtheirstructureactivityrelationship