Discovery of 4′-O-methylscutellarein as a potent SARS-CoV-2 main protease inhibitor

Wu, Qianqian; Yan, Shiqiang; Wang, Yujie; Li, Maotian; Xiao, Yibei; Li, Yingxia

doi:10.1016/j.bbrc.2022.03.052

Cited by 11 publications

(10 citation statements)

References 40 publications

(47 reference statements)

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“…Further SAR study demonstrated that the replacement of hydroxyl groups at the A-ring was indispensable, and hydrophobicity of the B-ring might be beneficial to inhibitory activity. 179 Xiong et al 96 identified myricetin, dihydromyricetin, and isodihydromyricetin as covalent inhibitors for SARS-CoV-2 3CL pro , whose orthoquinone form could modify the key cysteines near the catalytic site (Cys145) or dimeric interface (Cys300) of the target enzyme. Meanwhile, Su et al 180 also demonstrated that myricetin could covalently bind to Cys145 of SARS-CoV-2 3CL pro by using crystal structure analysis of the complex.…”

Section: Flavonoids and Their Derivativesmentioning

confidence: 99%

“…4′‐ O ‐methylscutellarein was characterized as a potent noncovalent 3CL pro inhibitor (IC 50 = 0.40 μM). Further SAR study demonstrated that the replacement of hydroxyl groups at the A‐ring was indispensable, and hydrophobicity of the B‐ring might be beneficial to inhibitory activity 179 . Xiong et al 96 .…”

Section: Naturally Derived Sars‐cov‐2 3clpro Inhibitorsmentioning

confidence: 99%

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The SARS‐CoV‐2 main protease (M^pro): Structure, function, and emerging therapies for COVID‐19

Xiong

Zhu

et al. 2022

MedComm

115

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The main proteases (Mpro), also termed 3‐chymotrypsin‐like proteases (3CLpro), are a class of highly conserved cysteine hydrolases in β‐coronaviruses. Increasing evidence has demonstrated that 3CLpros play an indispensable role in viral replication and have been recognized as key targets for preventing and treating coronavirus‐caused infectious diseases, including COVID‐19. This review is focused on the structural features and biological function of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) main protease Mpro (also known as 3CLpro), as well as recent advances in discovering and developing SARS‐CoV‐2 3CLpro inhibitors. To better understand the characteristics of SARS‐CoV‐2 3CLpro inhibitors, the inhibition activities, inhibitory mechanisms, and key structural features of various 3CLpro inhibitors (including marketed drugs, peptidomimetic, and non‐peptidomimetic synthetic compounds, as well as natural compounds and their derivatives) are summarized comprehensively. Meanwhile, the challenges in this field are highlighted, while future directions for designing and developing efficacious 3CLpro inhibitors as novel anti‐coronavirus therapies are also proposed. Collectively, all information and knowledge presented here are very helpful for understanding the structural features and inhibitory mechanisms of SARS‐CoV‐2 3CLpro inhibitors, which offers new insights or inspiration to medicinal chemists for designing and developing more efficacious 3CLpro inhibitors as novel anti‐coronavirus agents.

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Section: Flavonoids and Their Derivativesmentioning

confidence: 99%

Section: Naturally Derived Sars‐cov‐2 3clpro Inhibitorsmentioning

confidence: 99%

The SARS‐CoV‐2 main protease (M^pro): Structure, function, and emerging therapies for COVID‐19

Xiong

Zhu

et al. 2022

MedComm

115

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“…Thus, it was described that flavanoids—plant polyphenols Scutellarein, Dihydromyricetin, Quercetagetin, and Myricetin—are active against 3CLPro at a dose of 1.2–5.8 μM [ 50 ]. It has recently been shown that Scutellarein methylated at the 4′ position exhibits activity against the main protease at submicromolar concentrations [ 51 ]. In addition, it is known that the phenolic groups of polyphenols can be converted into orthoquinone under oxidizing conditions, which can be easily attacked by nucleophiles (e.g., the S-H group of the main protease) [ 52 ].…”

Section: Resultsmentioning

confidence: 99%

(+)-Usnic Acid and Its Derivatives as Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses

Filimonov

Yarovaya

Zaykovskaya

et al. 2022

Viruses

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In order to test the antiviral activity, a series of usnic acid derivatives were synthesized, including new, previously undescribed compounds. The activity of the derivatives against three strains of SARS-CoV-2 virus was studied. To understand the mechanism of antiviral action, the inhibitory activity of the main protease of SARS-CoV-2 virus was studied using the developed model as well as the antiviral activity against the pseudoviral system with glycoprotein S of SARS-CoV-2 virus on its surface. It was shown that usnic acid exhibits activity against three strains of SARS-CoV-2 virus: Wuhan, Delta, and Omicron. Compounds 10 and 13 also showed high activity against the three strains. The performed biological studies and molecular modeling allowed us to assume that the derivatives of usnic acid bind in the N-terminal domain of the surface glycoprotein S at the binding site of the hemoglobin decay metabolite.

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“…could effectively treat COVID-19, highlighting an important contributor to the active components (such as licorice-saponin A3, glycyrrhetinic acid, and so on) in herbal medicine treatment. (Wu et al, 2022b). Importantly, the results provided valuable data on the "multi-components, multiple-pathways, and multi-targets" feature of traditional herbal medicine.…”

Section: Promising Bioactive Natural Products In Covid-19 Therapymentioning

confidence: 92%

Bioactive natural products in COVID-19 therapy

Wang

Wang²,

Yang

et al. 2022

Front. Pharmacol.

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The devastating COVID-19 pandemic has caused more than six million deaths worldwide during the last 2 years. Effective therapeutic agents are greatly needed, yet promising magic bullets still do not exist. Numerous natural products (cordycepin, gallinamide A, plitidepsin, telocinobufagin, and tylophorine) have been widely studied and play a potential function in treating COVID-19. In this paper, we reviewed published studies (from May 2021 to April 2022) relating closely to bioactive natural products (isolated from medicinal plants, animals products, and marine organisms) in COVID-19 therapy in vitro to provide some essential guidance for anti-SARS-CoV-2 drug research and development.

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Discovery of 4′-O-methylscutellarein as a potent SARS-CoV-2 main protease inhibitor

Cited by 11 publications

References 40 publications

The SARS‐CoV‐2 main protease (M^pro): Structure, function, and emerging therapies for COVID‐19

The SARS‐CoV‐2 main protease (M^pro): Structure, function, and emerging therapies for COVID‐19

(+)-Usnic Acid and Its Derivatives as Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses

Bioactive natural products in COVID-19 therapy

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Discovery of 4′-O-methylscutellarein as a potent SARS-CoV-2 main protease inhibitor

Cited by 11 publications

References 40 publications

The SARS‐CoV‐2 main protease (Mpro): Structure, function, and emerging therapies for COVID‐19

The SARS‐CoV‐2 main protease (Mpro): Structure, function, and emerging therapies for COVID‐19

(+)-Usnic Acid and Its Derivatives as Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses

Bioactive natural products in COVID-19 therapy

Contact Info

Product

Resources

About

The SARS‐CoV‐2 main protease (M^pro): Structure, function, and emerging therapies for COVID‐19

The SARS‐CoV‐2 main protease (M^pro): Structure, function, and emerging therapies for COVID‐19