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

• Main Authors: Thi Thanh Hanh Nguyen, Jong-Hyun Jung, Min-Kyu Kim, Sangyong Lim, Jae-Myoung Choi, Byoungsang Chung, Do-Won Kim, Doman Kim
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Molecules
• Subjects: main protease; SARS-CoV-2; polyphenol; kinetic; structure–activity relationship; black garlic
• Online Access: https://www.mdpi.com/1420-3049/26/7/1924

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 <i>E. coli</i> BL21 (DE3). The optimal pH and temperature of M^pro were 7.5 and 37 °C, respectively. M^pro displayed a <i>K_m</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^pro. The IC₅₀ 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.