Identification of potent COVID-19 main protease (MPRO) inhibitors from flavonoids

Chauhan, Anita; Kalra, Seema

doi:10.21203/rs.3.rs-34497/v1

Cited by 11 publications

(10 citation statements)

References 13 publications

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“…Recent interest as an anti-influenza agent has been raised for this molecule, although no further development has been recorded 34 . Interestingly, the hypotheses that flavonoids could act as privileged scaffold for both SARS CoV and SARS CoV-2 3CL-Pro ligands 35,12 was confirmed in our investigations. In addition to baicalein, a series of flavonoids with IC50 ranging 180 nM to 3.6 μM (Table S3) were identified, and within this group myricetin derivatives were well represented.…”

Section: Compounds Inhibiting Sars-cov-2 3cl-prosupporting

confidence: 81%

Identification of inhibitors of SARS-CoV-2 3CL-Pro enzymatic activity using a small molecule in-vitro repurposing screen

Kuzikov

Costanzi

Reinshagen

et al. 2020

Preprint

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Compound repurposing is an important strategy for the identification of effective treatment options against SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (3CL-Pro), also termed M-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyproteins pp1a and pp1ab at multiple distinct cleavage sites. We here report the results of a repurposing program involving 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and small molecules regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, and have identified 62 additional compounds with IC50 values below 1 uM and profiled their selectivity towards Chymotrypsin and 3CL-Pro from the MERS virus. A subset of 8 inhibitors showed anti-cytopathic effect in a Vero-E6 cell line and the compounds thioguanosine and MG-132 were analysed for their predicted binding characteristics to SARS-CoV-2 3CL-Pro. The X-ray crystal structure of the complex of myricetin and SARS-Cov-2 3CL-Pro was solved at a resolution of 1.77 Angs., showing that myricetin is covalently bound to the catalytic Cys145 and therefore inhibiting its enzymatic activity.

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Section: Compounds Inhibiting Sars-cov-2 3cl-prosupporting

confidence: 81%

Identification of inhibitors of SARS-CoV-2 3CL-Pro enzymatic activity using a small molecule in-vitro repurposing screen

Kuzikov

Costanzi

Reinshagen

et al. 2020

Preprint

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“…With this regard many in silico studies were conducted to show and evaluate the efficacy of some active ingredients like flavonoids and some other natural products against SARS-CoV-2 M pro utilizing molecular docking technique. Taking in consideration the relative safe profile of these natural ingredients, these compounds could be be held in future as an outset for new therapeutics against COVID-19 [6,21]. In our previous study on the efficacy of vitamin D as is a potential inhibitor of SARS-CoV-2 endoribonuclease Nsp15, we found that Vitamin D is uniquely suppressed the three active sites in Nsp15 with significant advantageousness when compared to the other drugs utilized in treatment of COVID-19 like Remdesivir, Chloroquine, and Hydroxychloroquine [20].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D is a New Promising Inhibitor to the Main Protease (Mpro) of COVID-19 by Molecular Docking

Al-Mazaideh

Shalayel

Alswailmi

et al. 2021

JPRI

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In this study, vitamin D has shown greater efficacy of binding with Mpro of COVID-19 compared to the recently recommended drugs. The docking study was simulated to streamline interaction effects of Vitamin D, Remdesivir, Chloroquine, Hydroxychloroquine, Aspirin, and Azithromycin complexes with the active site of Mpro. Vitamin D is found to have the highest potential interaction in terms of total H-bond, van der Waal, torsional, and desolvation energy which were the lowest among all the selected drugs. The hydroxyl group of vitamin D and the thiol group of Mpro cysteine had played a leading role in increasing Vitamin D binding and stability with the Mpro pocket by contribution to the inception of three hydrogen bonds. The study recommend that vitamin D can be added to the COVID-19 treatment protocol, which may have the desired effect on viral replication inhibition and decreases mortality.

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“…Different virtual screening studies carried against Mpro enzyme have proposed several flavonoids like azithromycin, mangiferin, procyanidin-β-2,7-dimethoxyflavaN-4′-O-β-D-glucopyranoside, amentoflavone, hidrosmin, diosmin, gallocathechin gallate, elsamitrucin, pectolinaren, quercetin and isoquercetin having high binding affinities and thus could be used to combat the current situation. Along with the Mpro, ACE-2 is also a potential therapeutic target and flavonoids including hesperetin, myricetin, linebacker and caflanone have shown high binding affinity against ACE-2 making them important points of study against SARS-CoV-2 [ 119 , 120 ].…”

Section: Various Phytoconstituents That Are Being Studied For the Trementioning

confidence: 99%

Role of phytoconstituents in the management of COVID-19

Das

Pandita

Jain

et al. 2021

Chemico-Biological Interactions

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Background COVID-19, a severe global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as one of the most threatening transmissible disease. As a great threat to global public health, the development of treatment options has become vital, and a rush to find a cure has mobilized researchers globally from all areas. Scope and approach This review focuses on deciphering the potential of different secondary metabolites from medicinal plants as therapeutic options either as inhibitors of therapeutic targets of SARS-CoV-2 or as blockers of viral particles entry through host cell receptors. The use of medicinal plants containing specific phytomoieties could be seen in providing a safer and long-term solution for the population with lesser side effects. Key Findings and Conclusions : Considering the high cost and time-consuming drug discovery process, therapeutic repositioning of existing drugs was explored as treatment option in COVID-19, however several molecules have been retracted as therapeutics either due to no positive outcomes or the severe side effects. These effects call for exploring the alternate treatment options which are therapeutically effective as well as safe. Keeping this in mind, phytopharmaceuticals derived from medicinal plants could be explored as important resources in the development of COVID-19 treatment, as their role in the past for treatment of viral diseases like HIV, MERS-CoV, and influenza has been well reported. Considering this fact, different phytoconstituents such as flavonoids, alkaloids, tannins and glycosides etc. possessing antiviral properties against coronaviruses and possessing potential against SARS-CoV-2 have been reviewed in the present work.

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Identification of potent COVID-19 main protease (MPRO) inhibitors from flavonoids

Cited by 11 publications

References 13 publications

Identification of inhibitors of SARS-CoV-2 3CL-Pro enzymatic activity using a small molecule in-vitro repurposing screen

Identification of inhibitors of SARS-CoV-2 3CL-Pro enzymatic activity using a small molecule in-vitro repurposing screen

Vitamin D is a New Promising Inhibitor to the Main Protease (Mpro) of COVID-19 by Molecular Docking

Role of phytoconstituents in the management of COVID-19

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