Inhibition of SARS-CoV-2 main protease by phenolic compounds from <i>Manilkara hexandra</i> (Roxb.) Dubard assisted by metabolite profiling and <i>in silico</i> virtual screening

El-Mordy, Fatma M. Abd; El-Hamouly, M.M.A.; Ibrahim, Magda T.; El-Rheem, Gehad Abd; Aly, Omar M.; El-kader, Adel M. Abd; Youssif, Khayrya A.; Abdelmohsen, Usama Ramadan

doi:10.1039/d0ra05679k

Cited by 35 publications

(26 citation statements)

References 43 publications

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“…The COVID-19 pandemic started in December 2019 and has extended until now; there are no approved therapeutics for this disease. Although numerous researchers performed computational chemistry [ 45 ] and virtual screening of FDA-approved drugs [ 46 ] and flavonoid compounds [ 47 , 48 , 49 , 50 ] with M pro , their efficiencies against M pro need to be confirmed by in vitro and in vivo experiments. To the best of our knowledge, among our tested polyphenols, EGCG and tannic acid have been reported to have inhibitory effects on M pro with IC 50 values of 7.6 μg/mL and 2.1 μM, respectively [ 23 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…For example, Jang et al, (2020) performed the EGCG inhibition assay at 37 °C for 5 h using the same substrate; however, Coelho et al, (2020) conducted the inhibition assay using MCA-AVLQSGFR-K(Dnp)-K-NH 2 . Although we did not perform experiments to study the binding mode of these compounds by molecular docking, there are several reports that predict the inhibition mode of these compounds [ 48 , 49 , 50 ]. Molecular docking studies with M pro protein showed that some compounds, such as rutin (–9.2 kcal/mol), hesperidin (–8.1 kcal/mol), naringin (–8.1 kcal/mol), EGCG (–7.9 kcal/mol), catechin (–5.8 kcal/mol), myricetin (–5.9 kcal/mol), and caffeic acid (–5.1 kcal/mol), had the highest binding energy and hydrogen-bonding interactions with key amino acid residues of M pro [ 31 , 48 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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The main protease (Mpro) 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 Mpro was obtained as a 34.5 kDa protein by overexpression in E. coli BL21 (DE3). The optimal pH and temperature of Mpro were 7.5 and 37 °C, respectively. Mpro displayed a Km value of 16 μM with Dabcyl-KTSAVLQ↓SGFRKME-Edans. Black garlic extract and 49 polyphenols were studied for their inhibitory effects on purified Mpro. 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 Mpro. 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 Mpro.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Moreover, scientists are searching for possible drug targets to develop effective therapeutics to rapidly control this pandemic. The recent findings gave the scientific community a lot of information about SARS CoV-2 structural proteins, as well as those involved in viral nucleic acid replication and other host-specific proteins that have a vital role in the disease pathogenesis [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Cnicin as an Anti-SARS-CoV-2: An Integrated In Silico and In Vitro Approach for the Rapid Identification of Potential COVID-19 Therapeutics

et al. 2021

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Since the emergence of the SARS-CoV-2 pandemic in 2019, it has remained a significant global threat, especially with the newly evolved variants. Despite the presence of different COVID-19 vaccines, the discovery of proper antiviral therapeutics is an urgent necessity. Nature is considered as a historical trove for drug discovery, especially in global crises. During our efforts to discover potential anti-SARS CoV-2 natural therapeutics, screening our in-house natural products and plant crude extracts library led to the identification of C. benedictus extract as a promising candidate. To find out the main chemical constituents responsible for the extract’s antiviral activity, we utilized recently reported SARS CoV-2 structural information in comprehensive in silico investigations (e.g., ensemble docking and physics-based molecular modeling). As a result, we constructed protein–protein and protein–compound interaction networks that suggest cnicin as the most promising anti-SARS CoV-2 hit that might inhibit viral multi-targets. The subsequent in vitro validation confirmed that cnicin could impede the viral replication of SARS CoV-2 in a dose-dependent manner, with an IC50 value of 1.18 µg/mL. Furthermore, drug-like property calculations strongly recommended cnicin for further in vivo and clinical experiments. The present investigation highlighted natural products as crucial and readily available sources for developing antiviral therapeutics. Additionally, it revealed the key contributions of bioinformatics and computer-aided modeling tools in accelerating the discovery rate of potential therapeutics, particularly in emergency times like the current COVID-19 pandemic.

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“…Regarding 3CL pro , recent efforts, have identified potential inhibitors among: alkaloids [ 133 , 134 , 135 , 136 , 137 , 138 ], and especially indole alkaloids [ 139 , 140 , 141 , 142 , 143 , 144 ]; terpenoids [ 138 ], and especially diterpenes [ 133 , 145 ]; sesquiterpenes [ 134 , 146 , 147 ], sesquiterpene lactones [ 148 ], and triterpenes [ 133 , 136 , 140 , 149 ]; anthocyanins [ 150 , 151 ] and proanthocyanidins [ 152 , 153 ]; ellagitannins [ 153 , 154 ]; flavonoids [ 133 , 137 , 140 , 144 , 147 , 148 , 152 , 155 , 156 , 157 , 158 , 159 , 160 , 161 ], biflavonoids [ 162 ], and macrocyclic flavonoids [ 148 ]; isoflavones [ 144 , 148 ]; chalcones […”

Section: Nps With Anti-hcov Potentialmentioning

confidence: 99%

Natural and Nature-Derived Products Targeting Human Coronaviruses

et al. 2021

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The ongoing pandemic of severe acute respiratory syndrome (SARS), caused by the SARS-CoV-2 human coronavirus (HCoV), has brought the international scientific community before a state of emergency that needs to be addressed with intensive research for the discovery of pharmacological agents with antiviral activity. Potential antiviral natural products (NPs) have been discovered from plants of the global biodiversity, including extracts, compounds and categories of compounds with activity against several viruses of the respiratory tract such as HCoVs. However, the scarcity of natural products (NPs) and small-molecules (SMs) used as antiviral agents, especially for HCoVs, is notable. This is a review of 203 publications, which were selected using PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar, evaluates the available literature since the discovery of the first human coronavirus in the 1960s; it summarizes important aspects of structure, function, and therapeutic targeting of HCoVs as well as NPs (19 total plant extracts and 204 isolated or semi-synthesized pure compounds) with anti-HCoV activity targeting viral and non-viral proteins, while focusing on the advances on the discovery of NPs with anti-SARS-CoV-2 activity, and providing a critical perspective.

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Inhibition of SARS-CoV-2 main protease by phenolic compounds from Manilkara hexandra (Roxb.) Dubard assisted by metabolite profiling and in silico virtual screening

Abstract: SARS-CoV-2 is a novel coronavirus that was first identified during the outbreak in Wuhan, China in 2019.

Cited by 35 publications

References 43 publications

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

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

Cnicin as an Anti-SARS-CoV-2: An Integrated In Silico and In Vitro Approach for the Rapid Identification of Potential COVID-19 Therapeutics

Natural and Nature-Derived Products Targeting Human Coronaviruses

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