Shortlisting Phytochemicals Exhibiting Inhibitory Activity against Major Proteins of SARS-CoV-2 through Virtual Screening

Abstract Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) declared as a pandemic by WHO that has affected more than 40 lakh peoples and caused death of more than 2 lakh individuals across the globe. Limited availability of genomic information of SARS-CoV-2 and non-availability of vaccines and effective drugs are major problems responsible for the ineffective control and management of this pandemic. Several attempts have been made to explore repurposing existing drugs known for their anti-viral activities, and test the traditional herbal medicines known for their health benefiting and immune boosting activity against SARS-CoV-2.In this study, efforts were made to examine the potential of 721 phytochemicals of 37 plant species in inhibiting major protein targets namely, spike glycoprotein, main protease (MPro), NSP3, NSP9, NSP15, NSP10-NSP16 and RNA dependent RNA polymerase of SARS-CoV-2 through virtual screening approach. Results of our experiments revealed that SARS-CoV-2 MPro shared significant dissimilarities against SARS-CoVMPro and MERS-CoVMPro indicating the need for discovering novel drugs. This study has identified the phytochemical cyanin (Zingiber officinale) exhibiting broad spectrum inhibitory activity against main proteases of all the three Coronaviruses. Amentoflavone, agathisflavone, catechin-7-o-gallate and chlorogeninwere shown to exhibit multi target inhibitory activity. This study has identified Mangifera indica, Anacardium occidentale, Vitex negundo, Solanum nigrum, Pedalium murex, Terminalia chebula, Azadirachta indica, Cissus quadrangularis, Clerodendrum serratum and Ocimum basilicum as potential sources of phytochemicals combating nCOVID-19. More interestingly, this study has generated evidences for the anti-viral properties of the traditional herbal formulation “Kabasura kudineer” recommended by AYUSH, a unit of Government of India. Testing of short listed phytochemicals through clinical trials will help in developing effective formulation for management of this pandemic disease. Genomic analysis of identified herbal plants will help in unravelling molecular complexity of therapeutic and anti-viral properties and will pave way for designing synthetic drugs.

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Exploring Phytochemicals of Traditional Medicinal Plants Exhibiting Inhibitory Activity Against Main Protease, Spike Glycoprotein, RNA-dependent RNA Polymerase and Non-Structural Proteins of SARS-CoV-2 Through Virtual Screening

Frontiers in Pharmacology ◽

10.3389/fphar.2021.667704 ◽

2021 ◽

Vol 12 ◽

Author(s):

Saranya Nallusamy ◽

Jayakanthan Mannu ◽

Caroline Ravikumar ◽

Kandavelmani Angamuthu ◽

Bharathi Nathan ◽

...

Keyword(s):

Virtual Screening ◽

Inhibitory Activity ◽

Mangifera Indica ◽

Herbal Medicines ◽

Genomic Analysis ◽

Zingiber Officinale ◽

Binding Energies ◽

New Drugs ◽

Cissus Quadrangularis ◽

Scientific Attention

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) being a causative agent for global pandemic disease nCOVID’19, has acquired much scientific attention for the development of effective vaccines and drugs. Several attempts have been made to explore repurposing existing drugs known for their anti-viral activities, and test the traditional herbal medicines known for their health benefiting and immune-boosting activity against SARS-CoV-2. In this study, efforts were made to examine the potential of 605 phytochemicals from 37 plant species (of which 14 plants were endemic to India) and 139 antiviral molecules (Pubchem and Drug bank) in inhibiting SARS-CoV-2 multiple protein targets through a virtual screening approach. Results of our experiments revealed that SARS-CoV-2 MPro shared significant disimilarities against SARS-CoV MPro and MERS-CoV MPro indicating the need for discovering novel drugs. This study has screened the phytochemical cyanin (Zingiber officinale) which may exhibit broad-spectrum inhibitory activity against main proteases of SARS-CoV-2, SARS-CoV and MERS-CoV with binding energies of (−) 8.3 kcal/mol (−) 8.2 kcal/mol and (−) 7.7 kcal/mol respectively. Amentoflavone, agathisflavone, catechin-7-o-gallate and chlorogenin were shown to exhibit multi-target inhibitory activity. Further, Mangifera indica, Anacardium occidentale, Vitex negundo, Solanum nigrum, Pedalium murex, Terminalia chebula, Azadirachta indica, Cissus quadrangularis, Clerodendrum serratum and Ocimum basilicumaree reported as potential sources of phytochemicals for combating nCOVID’19. More interestingly, this study has highlighted the anti-viral properties of the traditional herbal formulation “Kabasura kudineer” recommended by AYUSH, a unit of Government of India. Short listed phytochemicals could be used as leads for future drug design and development. Genomic analysis of identified herbal plants will help in unraveling molecular complexity of therapeutic and anti-viral properties which proffer lot of chance in the pharmaceutical field for researchers to scout new drugs in drug discovery.

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EVALUATION OF XANTHINE OXIDASE INHIBITORY ACTIVITY BY FLAVONOIDS FROM PONGAMIA PINNATA LINN

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i3.16303 ◽

2017 ◽

Vol 10 (3) ◽

pp. 360 ◽

Cited By ~ 1

Author(s):

Vanishree Bambrana ◽

Dayanand Cd ◽

Sheela Sr

Keyword(s):

Xanthine Oxidase ◽

Plant Extracts ◽

Inhibitory Activity ◽

Mangifera Indica ◽

Zingiber Officinale ◽

Pongamia Pinnata ◽

Morinda Citrifolia ◽

Dried Fruit ◽

Fruit Powder ◽

Inhibitory Potential

ABSTRACTObjective: Flavonoids from the crude seeds extract of Pongamia pinnata L., dried fruit powder of Morinda citrifolia L., bark of Mangifera indica L., andrhizome of Zingiber officinale Rosc. were screened for xanthine oxidase (XO) inhibition at different concentration. The inhibitory potential of quercetinand allopurinol were used for the determination of 50% inhibitory concentration (IC50) and Ki values.Methods: Isolation of flavonoids from the plant extracts was processed by column chromatography and tested for XO inhibitory activity in the rangeof 6-800 μg/ml.Results: The results demonstrated that optimized flavonoids extract of P. pinnata L. exhibited promising XO inhibition. P. pinnata L., M. indica L., andZ. officinale Rosc. had IC50 in the concentration of 8.74 mM, 1.09 mM, 5.4 mM and Ki 0.35 mM, 1.73 mM, 2.7 mM, respectively.Conclusion: The study showed that plant species under investigation exhibited XO inhibition by optimized flavonoid extract. P. pinnata L. indicatedpromising XO inhibition compared to other plant extracts. Flavonoids can be used as a potent inhibitor of XO an alternative to allopurinol.Keywords: Xanthine oxidase, Quercetin, Allopurinol, Pongamia pinnata, Oxidative stress.

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Nephrotoxicity of Herbal Products in Europe—A Review of an Underestimated Problem of Nephrotoxicity of Herbal Products

International Journal of Molecular Sciences ◽

10.3390/ijms22084132 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4132

Author(s):

Katarzyna Kiliś-Pstrusińska ◽

Anna Wiela-Hojeńska

Keyword(s):

Kidney Diseases ◽

Herbal Medicines ◽

Kidney Injury ◽

Herbal Products ◽

Chronic Kidney Diseases ◽

European Origin ◽

Synthetic Drugs ◽

The Many ◽

Pharmacologically Active ◽

Traditional Chinese Herbal Medicines

Currently in Europe, despite the many advances in production technology of synthetic drugs, the interest in natural herbal medicines continues to increase. One of the reasons for their popular use is the assumption that natural equals safe. However, herbal medicines contain pharmacologically active ingredients, some of which have been associated with adverse effects. Kidneys are particularly susceptible to injury induced by toxins, including poisonous constituents from medicinal plants. The most recognized herb-induced kidney injury is aristolochic acid nephropathy connected with misuse of certain Traditional Chinese herbal medicines. Data concerning nephrotoxicity of plant species of European origin are scarce. Here, we critically review significant data of the nephrotoxicity of several plants used in European phytotherapy, including Artemisia herba-alba, Glycyrrhiza glabra, Euphorbia paralias, and Aloe). Causative mechanisms and factors predisposing to intoxications from the use of herbs are discussed. The basic intention of this review is to improve pharmacovigilance of herbal medicine, especially in patients with chronic kidney diseases.

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The inhibitory activity of herbal medicines on the keys enzymes and steps related to carbohydrate and lipid digestion

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-016-1424-2 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 8

Author(s):

Weerachat Sompong ◽

Nuttapat Muangngam ◽

Artitaya Kongpatpharnich ◽

Chadakarn Manacharoenlarp ◽

Chanatkarn Amorworasin ◽

...

Keyword(s):

Inhibitory Activity ◽

Herbal Medicines ◽

Lipid Digestion

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A comprehensive review on the medicinal importance; biological and therapeutic efficacy of Lagenaria siceraria (Mol.) (bottle gourd) Standley fruit

Current Topics in Medicinal Chemistry ◽

10.2174/1568026621666210701124628 ◽

2021 ◽

Vol 21 ◽

Author(s):

Muhammad Zahoor ◽

Muhammad Ikram ◽

Nausheen Nazir ◽

Sumaira Naz ◽

Gaber El-Saber Batiha ◽

...

Keyword(s):

Herbal Medicines ◽

High Water ◽

Bottle Gourd ◽

Herbal Remedies ◽

Lagenaria Siceraria ◽

Synthetic Drugs ◽

Domestic Plant ◽

Phytochemical Constituents ◽

Cucurbitaceae Family ◽

Water Contents

: Herbal remedies have been employed for the treatment and management of different diseases for ages. Herbal medicines are a promising choice over modern synthetic drugs because of their low side effects and are thus considered safe and effective in treating human diseases. Lagenaria siceraria (Mol.) Standley fruit (Bottle gourd) belongs to the Cucurbitaceae family that has been used in a different system of traditional medication to treat various diseases. This is a domestic plant that provides food as well as medication. This vegetable has low caloric values and high water contents. The edible portion of it contains phytochemicals like vitamins, proteins, choline, minerals, terpenoids, flavonoids etc. Several bioactive compounds have been isolated from L. siceraria, including triterpenoids, sterols, cucurbitacins, flavones, C-glycosides and β-glycosides. Researchers have evaluated various parts of this plant viz., fruit, root, flowers, and leaves for pharmacological activities like antianxiety, antidepressant, diuretic, antimicrobial, cytotoxic, antihyperlipidemic, cardioprotective, analgesic, anti-inflammatory, anthelmintic, anti-hyperglycemic, antihepatotoxic, anti-urolithiatic, antistress, antiulcer, anticancer, hepatoprotective, anthelmintic, immunomodulatory, and antioxidant. In this review, an attempt has been made to explore its phytochemical constituents, traditional, medicinal, and pharmacological uses to highlight the therapeutic importance of this well-known plant. This would be helpful in reviving its importance and highlight its several promising aspects to encourage researchers for further research on L. siceraria.

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Natural products as inhibitors of COVID-19 main protease – A virtual screening by molecular docking

10.21203/rs.3.rs-57351/v1 ◽

2020 ◽

Author(s):

Marzieh omrani ◽

Mohammad Bayati ◽

Parvaneh Mehrbod ◽

Samad Nejad-Ebrahimi

Keyword(s):

Natural Products ◽

Virtual Screening ◽

High Throughput ◽

Herbal Medicines ◽

Respiratory Illness ◽

Fast Method ◽

Main Protease ◽

Glide Docking ◽

Adme Properties ◽

High Throughput Virtual Screening

Abstract Background: The novel coronavirus (2019-nCoV) causes a severe respiratory illness that was unknown in the human before. Its alarmingly quick transmission to many countries across the world resulted in a worldwide health emergency. It has caused a notable percentage of morbidity and mortality. Therefore, an imminent need for drugs to combat this disease has been increased. Global collaborative efforts from scientists are underway to find a therapy to treat infections and reduce death cases. Herbal medicines and purified natural products have been reported to have antiviral activity against Coronaviruses (CoVs).Methods: In this study, a High Throughput Virtual Screening (HTVS) protocol was used as a fast method on the discovery of novel drug candidates as the COVID-19 main protease inhibitors. Over 180,000 natural product-based compounds were obtained from the ZINC database and virtually screened against the COVID-19 main protease. In this study, the Glide docking program was applied for high throughput virtual screening. Extra precision (XP) and in a combination of Prime module, induced-fit docking (IFD) approach was also used. Additionally, the ADME properties of all compounds were analyzed, and the final selection was carried out based on the Lipinski rule of five. Results: The nineteen compounds were selected and introduced as new potential inhibitors. The compound ZINC08765174 (1-[3-(1H-indol-3-yl) propanoyl]-N-(4-phenylbutan-2-yl)piperidine-3-carboxamide) showed a strong binding affinity (-11.5 kcal/mol) to the crucial residues of COVID-19 main protease comparing to peramivir (-9.8 kcal/mol) as a positive control.Conclusions: The excellent ADME properties proposed the opportunity of this compound to be a promising candidate for the treatment of COVID-19.

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Phenolic composition and inhibitory activity of Mangifera indica and Mucuna urens seeds extracts against key enzymes linked to the pathology and complications of type 2 diabetes

Asian Pacific Journal of Tropical Biomedicine ◽

10.12980/apjtb.4.201414b364 ◽

2014 ◽

Vol 4 (11) ◽

pp. 903-910 ◽

Cited By ~ 16

Author(s):

Emmanuel Anyachukwu Irondi ◽

Ganiyu Oboh ◽

Afolabi Akintunde Akindahunsi ◽

Aline Augusti Boligon ◽

Margareth Linde Athayde

Keyword(s):

Type 2 Diabetes ◽

Inhibitory Activity ◽

Mangifera Indica ◽

Phenolic Composition ◽

Key Enzymes

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SEARCHING BY METOD OF NEURAL NETWORK MODELING OF CONDENSED BENZIMIDAZOLE DERIVATIVES WITH MULTI-TARGET RAGE-INHIBITORY ACTIVITY

BIOTECHNOLOGY: STATE OF THE ART AND PERSPECTIVES ◽

10.37747/2312-640x-2020-18-248-249 ◽

2020 ◽

pp. 248-249

Author(s):

O. Zhukovskaya ◽

A. Spasov ◽

A. Morkovnik ◽

A. Kochetkov

Keyword(s):

Neural Network ◽

Virtual Screening ◽

Network Model ◽

Neural Network Model ◽

Inhibitory Activity ◽

Network Modeling ◽

Inhibitory Effect ◽

Benzimidazole Derivatives ◽

Neural Network Modeling

Using a multitarget neural network model of RAGE-inhibitory activity, a consensus virtual screening of a library of new condensed benzimidazole derivatives was performed. Compounds with a essential RAGE-inhibitory effect have been found.

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