Phytonutrient Inhibitors of SARS-CoV-2/NSP5-Encoded Main Protease (Mpro) Autocleavage Enzyme Critical for COVID-19 Pathogenesis
The genomic reshuffling, mutagenicity, and high transmission rate of the SARS-CoV-2 pathogen highlights an urgent need for effective antiviral interventions for COVID-19 control. Targeting the highly conserved viral genes and/or gene-encoded viral proteins such as main proteinase (Mpro), RNA-dependent RNA polymerase (RdRp) and helicases are plausible antiviral approaches to prevent replication and propagation of the SARS-CoV-2 infection. Coronaviruses (CoVs) are prone to extensive mutagenesis; however, any genetic alteration to its highly conserved Mpro enzyme is often detrimental to the viral pathogen. Therefore, inhibitors that target the Mpro enzyme could reduce the risk of mutation-mediated drug resistance and provide effective antiviral protection. Several existing antiviral drugs and dietary bioactives are currently repurposed to treat COVID-19. Dietary bioactives from three ayurvedic medicinal herbs, 18 β-glycyrrhetinic acid (ΔG = 8.86 kcal/mol), Solanocapsine (ΔG = 8.59 kcal/mol), and Vasicoline (ΔG = 7.34 kcal/mol), showed high-affinity binding to Mpro enzyme than the native N3 inhibitor (ΔG = 5.41 kcal/mol). Flavonoids strongly inhibited SARS-CoV-2 Mpro with comparable or higher potency than the antiviral drug, remdesivir. Several tannin hydrolysates avidly bound to the receptor-binding domain and catalytic dyad (His41 and Cys145) of SARS-CoV-2 Mpro through H-bonding forces. Quercetin binding to Mpro altered the thermostability of the viral protein through redox-based mechanism and inhibited the viral enzymatic activity. Interaction of quercetin-derivatives with the Mpro seem to be influenced by the 7-OH group and the acetoxylation of sugar moiety on the ligand molecule. Based on pharmacokinetic and ADMET profiles, several phytonutrients could serve as a promising redox nutraceutical for COVID-19 management.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
---|---|
Enthalten in: |
Journal of dietary supplements - 20(2023), 2 vom: 01., Seite 284-311 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Naidu, Sreus A G [VerfasserIn] |
---|
Links: |
---|
Themen: |
9IKM0I5T1E |
---|
Anmerkungen: |
Date Completed 21.03.2023 Date Revised 21.03.2023 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1080/19390211.2021.2006388 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM33358693X |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM33358693X | ||
003 | DE-627 | ||
005 | 20231225221941.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1080/19390211.2021.2006388 |2 doi | |
028 | 5 | 2 | |a pubmed24n1111.xml |
035 | |a (DE-627)NLM33358693X | ||
035 | |a (NLM)34821532 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Naidu, Sreus A G |e verfasserin |4 aut | |
245 | 1 | 0 | |a Phytonutrient Inhibitors of SARS-CoV-2/NSP5-Encoded Main Protease (Mpro) Autocleavage Enzyme Critical for COVID-19 Pathogenesis |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 21.03.2023 | ||
500 | |a Date Revised 21.03.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a The genomic reshuffling, mutagenicity, and high transmission rate of the SARS-CoV-2 pathogen highlights an urgent need for effective antiviral interventions for COVID-19 control. Targeting the highly conserved viral genes and/or gene-encoded viral proteins such as main proteinase (Mpro), RNA-dependent RNA polymerase (RdRp) and helicases are plausible antiviral approaches to prevent replication and propagation of the SARS-CoV-2 infection. Coronaviruses (CoVs) are prone to extensive mutagenesis; however, any genetic alteration to its highly conserved Mpro enzyme is often detrimental to the viral pathogen. Therefore, inhibitors that target the Mpro enzyme could reduce the risk of mutation-mediated drug resistance and provide effective antiviral protection. Several existing antiviral drugs and dietary bioactives are currently repurposed to treat COVID-19. Dietary bioactives from three ayurvedic medicinal herbs, 18 β-glycyrrhetinic acid (ΔG = 8.86 kcal/mol), Solanocapsine (ΔG = 8.59 kcal/mol), and Vasicoline (ΔG = 7.34 kcal/mol), showed high-affinity binding to Mpro enzyme than the native N3 inhibitor (ΔG = 5.41 kcal/mol). Flavonoids strongly inhibited SARS-CoV-2 Mpro with comparable or higher potency than the antiviral drug, remdesivir. Several tannin hydrolysates avidly bound to the receptor-binding domain and catalytic dyad (His41 and Cys145) of SARS-CoV-2 Mpro through H-bonding forces. Quercetin binding to Mpro altered the thermostability of the viral protein through redox-based mechanism and inhibited the viral enzymatic activity. Interaction of quercetin-derivatives with the Mpro seem to be influenced by the 7-OH group and the acetoxylation of sugar moiety on the ligand molecule. Based on pharmacokinetic and ADMET profiles, several phytonutrients could serve as a promising redox nutraceutical for COVID-19 management | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Antiviral | |
650 | 4 | |a Ayurvedic Medicine | |
650 | 4 | |a COVID-19 | |
650 | 4 | |a Mpro | |
650 | 4 | |a Phytonutrients | |
650 | 4 | |a Quercetin | |
650 | 4 | |a Redox nutraceutical | |
650 | 4 | |a SARS-CoV-2 | |
650 | 7 | |a Quercetin |2 NLM | |
650 | 7 | |a 9IKM0I5T1E |2 NLM | |
650 | 7 | |a Antiviral Agents |2 NLM | |
650 | 7 | |a Peptide Hydrolases |2 NLM | |
650 | 7 | |a EC 3.4.- |2 NLM | |
650 | 7 | |a Phytochemicals |2 NLM | |
700 | 1 | |a Tripathi, Yamini B |e verfasserin |4 aut | |
700 | 1 | |a Shree, Priya |e verfasserin |4 aut | |
700 | 1 | |a Clemens, Roger A |e verfasserin |4 aut | |
700 | 1 | |a Naidu, A Satyanarayan |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Journal of dietary supplements |d 2008 |g 20(2023), 2 vom: 01., Seite 284-311 |w (DE-627)NLM192571656 |x 1939-022X |7 nnns |
773 | 1 | 8 | |g volume:20 |g year:2023 |g number:2 |g day:01 |g pages:284-311 |
856 | 4 | 0 | |u http://dx.doi.org/10.1080/19390211.2021.2006388 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 20 |j 2023 |e 2 |b 01 |h 284-311 |