scholarly journals Ayurveda botanicals in COVID-19 management: An in silico multi-target approach

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0248479
Author(s):  
Swapnil Borse ◽  
Manali Joshi ◽  
Akash Saggam ◽  
Vedika Bhat ◽  
Safal Walia ◽  
...  
Keyword(s):  
In Silico ◽  
Specific Treatment ◽  
Protective Role ◽  
Tinospora Cordifolia ◽  
Network Pharmacology ◽  
Asparagus Racemosus ◽  
Global Pandemic ◽  
Main Protease ◽  
Short Time Span ◽  
Short Time

The Coronavirus disease (COVID-19) caused by the virus SARS-CoV-2 has become a global pandemic in a very short time span. Currently, there is no specific treatment or vaccine to counter this highly contagious disease. There is an urgent need to find a specific cure for the disease and global efforts are directed at developing SARS-CoV-2 specific antivirals and immunomodulators. Ayurvedic Rasayana therapy has been traditionally used in India for its immunomodulatory and adaptogenic effects, and more recently has been included as therapeutic adjuvant for several maladies. Amongst several others, Withania somnifera (Ashwagandha), Tinospora cordifolia (Guduchi) and Asparagus racemosus (Shatavari) play an important role in Rasayana therapy. The objective of this study was to explore the immunomodulatory and anti SARS-CoV2 potential of phytoconstituents from Ashwagandha, Guduchi and Shatavari using network pharmacology and docking. The plant extracts were prepared as per ayurvedic procedures and a total of 31 phytoconstituents were identified using UHPLC-PDA and mass spectrometry studies. To assess the immunomodulatory potential of these phytoconstituents an in-silico network pharmacology model was constructed. The model predicts that the phytoconstituents possess the potential to modulate several targets in immune pathways potentially providing a protective role. To explore if these phytoconstituents also possess antiviral activity, docking was performed with the Spike protein, Main Protease and RNA dependent RNA polymerase of the virus. Interestingly, several phytoconstituents are predicted to possess good affinity for the three targets, suggesting their application for the termination of viral life cycle. Further, predictive tools indicate that there would not be adverse herb-drug pharmacokinetic-pharmacodynamic interactions with concomitantly administered drug therapy. We thus make a compelling case to evaluate the potential of these Rasayana botanicals as therapeutic adjuvants in the management of COVID-19 following rigorous experimental validation.

scholarly journals Ayurveda botanicals in COVID-19 management: An in silico- multitarget approach

2020 ◽  
Author(s):  
Swapnil Borse ◽  
Manali Joshi ◽  
Akash Saggam ◽  
Vedika Bhat ◽  
Safal Walia ◽  
...  
Keyword(s):  
T Cell ◽  
In Silico ◽  
Withania Somnifera ◽  
Nk Cell ◽  
Specific Treatment ◽  
Docking Studies ◽  
Tinospora Cordifolia ◽  
Network Pharmacology ◽  
Asparagus Racemosus ◽  
Disease Modifying Agents

Abstract The Coronavirus disease (COVID-19) caused by the virus SARS-CoV-2 has become a global pandemic in a very short time span. Currently, there is no specific treatment or vaccine to counter this highly contagiousdisease. Presently, existing anti-virals and disease-modifying agents are being repurposed to manage COVID-19. There is an urgent need to find a specific cure for the disease and global efforts are directed at developing SARS-CoV-2 specific anti-viralsand immunomodulators.The objective of this study is to explore the immunomodulatory and anti-SARS-CoV-2 potential of key phytoconstituents from Ayurveda based Rasayana drugs, Withania somnifera (Ashwagandha), Tinospora cordifolia (Guduchi) and Asparagus racemosus (Shatavari) using in silico approaches like network pharmacology, and molecular docking. The SWISS-ADME tool was used to predict the pharmacokinetic and pharmacodynamic (PK-PD) interactions and drug likeliness potential. Using these approaches we propose a library of phytomolecules with potential to be developed as phytopharmaceuticals for COVID 19 management.The plant extracts were prepared as per Ayurvedic procedures and a total of 31 phytoconstituents were identified using HPLC and MS studies. The network pharmacology model shows that these phytoconstituents possess the potential to modulate several immune pathways. Amongst the three botanicalsWithania somnifera was found to be the most potent immunomodulator through its potential to modulate T cell differentiation, NK cell cytotoxicity as well as T cell, B cell and NOD-like receptor signalling pathways.Molecular docking studies showed thatseveral phytoconstituents possess good affinity for the Spike protein, Main Protease and RNA dependent RNA polymerase of SARS-CoV-2 suggesting their application for the termination of viral life cycle. Further, predictive tools indicate that there would beneficial herb-drug pharmacokinetic-pharmacodynamic interactions with concomitantly administered drug therapy. We thus make a compelling case to evaluate the potential of these Rasayana botanicals in the management of COVID-19 following rigorous experimental validation.

scholarly journals Identification of Bioactive Phytoconstituents from the Plant Euphorbia hirta as Potential Inhibitor of SARS-CoV-2: an In-Silico Approach

2021 ◽  
Vol 12 (2) ◽  
pp. 1385-1396
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Biological Activities ◽  
Specific Treatment ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Euphorbia Hirta ◽  
Main Protease

Currently, the entire globe is under the deadliest pandemic of Covid-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). At present, no specific treatment is available to combat COVID-19 infection. Euphorbia hirta (Euphorbiaceae) have been reported for a variety of biological activities, including antiviral. The present investigation aimed to identify potential phytoconstituents of the plant E. hirta from the category flavonoids and coumarins against the SARS-CoV-2 using in silico approach. The molecular docking studies were performed using two different targets of SARS-CoV-2, namely Main protease (Mpro; PDB ID: 6M2N) and RNA-dependent RNA polymerase (RdRp; PDB ID: 7BW4). Based on the molecular docking study in comparison with standard drug, four compounds, namely Euphrobianin, Quercetin, 3-o-alpha-rhamnoside, Isoquercitrin, and rutin, were screened against the target Mpro. Three phytoconstituents, euphorbianin, myricetin, and rutin, were screened against the target RdRp. In the in silico toxicity studies of screened phytoconstituents, except myrectin all were predicted safe. Results of euphorbianin and rutin were found more interesting as both compounds had high binding affinity against both targets. Finally, we want to conclude that euphrobianin, quercetin 3-o-alpha-rhamnoside, isoquercitrin, and rutin could be further explored rapidly as they may have the potential to fight against COVID-19.

scholarly journals In Silico Exploration of Repurposing and Optimizing Traditional Chinese Medicine Rutin for Possibly Inhibiting SARS-CoV-2's Main Protease

2020 ◽  
Author(s):  
Tien Huynh ◽  
Haoran Wang ◽  
Wendy Cornell ◽  
Binquan Luan
Keyword(s):  
In Silico ◽  
Molecular Mechanisms ◽  
Herbal Medicines ◽  
Viral Proteins ◽  
Biological Functions ◽  
Rna Dependent Rna Polymerase ◽  
Global Pandemic ◽  
Main Protease ◽  
Dynamics Simulations ◽  
Viral Target

<div>Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic with very limited specific treatments. To fight COVID-19, various traditional antiviral medicines haveb been prescribed in China to infected patients with mild to moderate symptoms and received unexpected success in controlling the disease. However, the molecular mechanisms of how these herbal medicines interact with the virus have remained elusive. It is well known that the main protease (Mpro) of SARS-CoV-2 plays an important role in maturation of many viral proteins such as the RNA-dependent RNA polymerase. Here,we explore the underlying molecular mechanisms of the computationally determined top candidate–rutin, a key component in many traditional antiviral medicines such as Lianhuaqinwen and Shuanghuanlian, for inhibiting the viral target–Mpro. Using in silico methods (docking and molecular dynamics simulations), we revealed the dynamics and energetics of rutin when interacting with the Mpro of SARS-CoV-2, suggesting that the highly hydrophilic rutin molecule can be bound inside the Mpro’ pocket (active site) and possibly inhibit its biological functions. In addition, we optimized the structure of rutin and designed a more hydrophobic analog which satisfies the rule of five for western medicines and demonstrated that it possesses a much stronger binding affinity to the SARS-COV-2’s Mpro.<br></div>

Anti-Corona's Drug Virtual Screening

2020 ◽  
Author(s):  
Farah Yousef ◽  
oussama mansour
Keyword(s):  
Virtual Screening ◽  
In Silico ◽  
Respiratory Symptoms ◽  
Clinical Effectiveness ◽  
Herbal Drugs ◽  
Global Pandemic ◽  
Short Time ◽  
Effective Drugs

Coronavirus (COVID-19, SARS-COV-2) has become in short time a global pandemic. It causes after two weeks of exposure severe respiratory symptoms. Herbal and non-herbal drugs were tested for treatment of coronavirus. In this study, we in-silico investigated seven clinically effective drugs used to get control of the coronavirus cases. Five of them had bonds to the main core of coronavirus protease. This can interpret the clinical effectiveness of these drugs used as monotherapy or combined one and assist in discovering more effective drugs against this unseen assassin.

scholarly journals Flavonoid compounds of buah merah (Pandanus conoideus Lamk) as a potent SARS-CoV-2 main protease inhibitor: in silico approach

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Abd. Kakhar Umar
Keyword(s):  
Protein Interactions ◽  
In Silico ◽  
Antiviral Drug ◽  
Pharmacokinetic Profile ◽  
Unbound Fraction ◽  
Receptor Complexes ◽  
Flavonoid Compounds ◽  
Global Pandemic ◽  
Main Protease ◽  
Low Toxicity

Abstract Background COVID19 is a global pandemic that threatens all nations. As there is no effective antiviral drug for COVID19, we examined the potency of natural ingredients against the SARS-CoV-2 main protease (PDB ID 6YNQ). Buah merah is a typical fruit from Papua, Indonesia, which is known to contain high levels of carotenoids and flavonoids. The contents have been proven to be effective as antiparasitic and anti-HIV. An in silico approach to 16 metabolites of buah merah (Pandanus conoideus Lamk) was carried out using AutoDock Vina. Furthermore, the study of the dynamics of ligand–protein interactions was carried out using CABS Flex 2.0 server to determine the test ligand and receptor complexes' stability. ADMET prediction was also carried out to study the pharmacokinetic profile of potential antiviral candidates. Result The docking results showed that 3 of the 16 buah merah metabolites were potent inhibitors against the SARS-CoV-2 main protease. The flavonoid compounds are quercetin 3′-glucoside, quercetin 3-O-glucose, and taxifolin 3-O-α-arabinopyranose with a binding affinity of − 9.7, − 9.3, and − 8.8, respectively, with stable ligand–protein complex. ADMET study shows that the three compounds are easily dissolved, easily absorbed orally and topically, have a high unbound fraction, low toxicity, and non-irritant. Conclusion We conclude that quercetin 3′-glucoside, quercetin 3-O-glucose, and taxifolin 3-O-α-arabinopyranose can be used and improved as potential anti-SARS-CoV-2 agents in further study.

In Silico Exploration of Molecular Mechanism and Potency Ranking of Clinically Oriented Drugs for Inhibiting SARS-CoV-2’s Main Protease

2020 ◽  
Author(s):  
Tien Huynh ◽  
haoran wang ◽  
Binquan Luan
Keyword(s):  
Ligand Binding ◽  
In Silico ◽  
Fast Response ◽  
Binding Mechanism ◽  
Biological Functions ◽  
Drug Molecules ◽  
Global Pandemic ◽  
Main Protease ◽  
Potency Ranking ◽  
High Binding Affinity

<p>Currently, the new coronavirus disease 2019 (COVID-19) is a global pandemic without any well calibrated treatment. To inactivate the SARS-CoV-2 virus that causes COVID-19, the main protease (Mpro) that performs key biological functions in the virus has been the focus of extensive studies. With the fast-response experimental efforts, the crystal structures of Mpro of the SARS-CoV-2 virus have just become available recently. Herein, we theoretically investigated the binding mechanism between the Mpro's pocket and various marketed drug molecules being tested in clinics to fight COVID-19 that show promising outcomes. Combining all existing experiment results with our computational ones, we revealed an important ligand-binding mechanism for the Mpro that the binding stability of a ligand inside the Mpro pocket can be significantly improved if the partial ligand occupies the so-called "anchor" site of the Mpro. Along with the high-potent drugs/molecules (such as nelfinavir and curcumin) revealed in this study, the newly discovered binding mechanism paves the way for further optimizations and designs of Mpro's inhibitors with a high binding affinity. </p>

scholarly journals In Silico Exploration of Molecular Mechanism and Potency Ranking of Clinically Oriented Drugs for Inhibiting SARS-CoV-2’s Main Protease

2020 ◽  
Author(s):  
Tien Huynh ◽  
haoran wang ◽  
Binquan Luan
Keyword(s):  
Ligand Binding ◽  
In Silico ◽  
Fast Response ◽  
Binding Mechanism ◽  
Biological Functions ◽  
Drug Molecules ◽  
Global Pandemic ◽  
Main Protease ◽  
Potency Ranking ◽  
High Binding Affinity

<p>Currently, the new coronavirus disease 2019 (COVID-19) is a global pandemic without any well calibrated treatment. To inactivate the SARS-CoV-2 virus that causes COVID-19, the main protease (Mpro) that performs key biological functions in the virus has been the focus of extensive studies. With the fast-response experimental efforts, the crystal structures of Mpro of the SARS-CoV-2 virus have just become available recently. Herein, we theoretically investigated the binding mechanism between the Mpro's pocket and various marketed drug molecules being tested in clinics to fight COVID-19 that show promising outcomes. Combining all existing experiment results with our computational ones, we revealed an important ligand-binding mechanism for the Mpro that the binding stability of a ligand inside the Mpro pocket can be significantly improved if the partial ligand occupies the so-called "anchor" site of the Mpro. Along with the high-potent drugs/molecules (such as nelfinavir and curcumin) revealed in this study, the newly discovered binding mechanism paves the way for further optimizations and designs of Mpro's inhibitors with a high binding affinity. </p>

Anti-Corona's Drug Virtual Screening

2020 ◽  
Author(s):  
Farah Yousef ◽  
Oussama Mansou
Keyword(s):  
Virtual Screening ◽  
In Silico ◽  
Respiratory Symptoms ◽  
Clinical Effectiveness ◽  
Herbal Drugs ◽  
Global Pandemic ◽  
Short Time ◽  
Effective Drugs

Coronavirus (COVID-19, SARS-COV-2) has become in short time a global pandemic. It causes after two weeks of exposure severe respiratory symptoms. Herbal and non-herbal drugs were tested for treatment of coronavirus. In this study, we in-silico investigated seven clinically effective drugs used to get control of the coronavirus cases. Five of them had bonds to the main core of coronavirus protease. This can interpret the clinical effectiveness of these drugs used as monotherapy or combined one and assist in discovering more effective drugs against this unseen assassin.

Anti-Corona's Drug Virtual Screening

2020 ◽  
Author(s):  
Farah Yousef ◽  
oussama mansour
Keyword(s):  
Virtual Screening ◽  
In Silico ◽  
Respiratory Symptoms ◽  
Clinical Effectiveness ◽  
Herbal Drugs ◽  
Global Pandemic ◽  
Short Time ◽  
Effective Drugs

Coronavirus (COVID-19, SARS-COV-2) has become in short time a global pandemic. It causes after two weeks of exposure severe respiratory symptoms. Herbal and non-herbal drugs were tested for treatment of coronavirus. In this study, we in-silico investigated seven clinically effective drugs used to get control of the coronavirus cases. Five of them had bonds to the main core of coronavirus protease. This can interpret the clinical effectiveness of these drugs used as monotherapy or combined one and assist in discovering more effective drugs against this unseen assassin.

scholarly journals In Silico Exploration of Repurposing and Optimizing Traditional Chinese Medicine Rutin for Possibly Inhibiting SARS-CoV-2's Main Protease

2020 ◽  
Author(s):  
Tien Huynh ◽  
Haoran Wang ◽  
Wendy Cornell ◽  
Binquan Luan
Keyword(s):  
In Silico ◽  
Molecular Mechanisms ◽  
Herbal Medicines ◽  
Viral Proteins ◽  
Biological Functions ◽  
Rna Dependent Rna Polymerase ◽  
Global Pandemic ◽  
Main Protease ◽  
Dynamics Simulations ◽  
Viral Target

<div>Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic with very limited specific treatments. To fight COVID-19, various traditional antiviral medicines haveb been prescribed in China to infected patients with mild to moderate symptoms and received unexpected success in controlling the disease. However, the molecular mechanisms of how these herbal medicines interact with the virus have remained elusive. It is well known that the main protease (Mpro) of SARS-CoV-2 plays an important role in maturation of many viral proteins such as the RNA-dependent RNA polymerase. Here,we explore the underlying molecular mechanisms of the computationally determined top candidate–rutin, a key component in many traditional antiviral medicines such as Lianhuaqinwen and Shuanghuanlian, for inhibiting the viral target–Mpro. Using in silico methods (docking and molecular dynamics simulations), we revealed the dynamics and energetics of rutin when interacting with the Mpro of SARS-CoV-2, suggesting that the highly hydrophilic rutin molecule can be bound inside the Mpro’ pocket (active site) and possibly inhibit its biological functions. In addition, we optimized the structure of rutin and designed a more hydrophobic analog which satisfies the rule of five for western medicines and demonstrated that it possesses a much stronger binding affinity to the SARS-COV-2’s Mpro.<br></div>

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