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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307181

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 botanicals Withania 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.

2.
PLoS One ; 16(6): e0248479, 2021.
Article in English | MEDLINE | ID: covidwho-1266543

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 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.


Subject(s)
Antiviral Agents/metabolism , Asparagus Plant/chemistry , COVID-19/metabolism , Immunologic Factors/metabolism , Molecular Docking Simulation/methods , Plant Extracts/metabolism , SARS-CoV-2/enzymology , Tinospora/chemistry , Withania/chemistry , Antiviral Agents/pharmacokinetics , Binding Sites , COVID-19/drug therapy , COVID-19/virology , Coronavirus 3C Proteases/metabolism , Coronavirus RNA-Dependent RNA Polymerase/metabolism , Herb-Drug Interactions , Humans , Immunologic Factors/pharmacokinetics , India , Medicine, Ayurvedic/methods , Phytotherapy/methods , Plant Extracts/pharmacokinetics , Protein Binding , Spike Glycoprotein, Coronavirus/metabolism
3.
Heliyon ; 7(3): e06564, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1141868

ABSTRACT

The mortality rates due to COVID-19 have been found disproportionate globally and are currently being researched. India mortality rate with a population of 1.3 billion people is relatively lowest to other countries with high infection rates. Genetic composition of circulating isolates continues to be a key determinant of virulence and pathogenesis. This study aimed to analyse the extent of divergence between genomes of Indian isolates (n = 2525 as compared to reference Wuhan-1 strain and isolates from countries showing higher fatality rates including France, Italy, Belgium, and the USA. The study also analyses the impact of key mutations on interactions with angiotensin converting enzyme 2 (ACE2) and panel of neutralizing monoclonal antibodies. Using 1,44,605 spike protein sequences, global prevalence of mutations in spike protein was observed. The study suggests that SARS-CoV-2 genomes from India share consensus with global trends with respect to D614G as most prevalent mutational event (81.66% among 2525 Indian isolates). Indian isolates did not reported prevalence of N439K mutation in receptor binding motif (RBM) as compared to global isolates (0.54%). Computational docking and molecular dynamics simulation analysis of N439K mutation with respect to ACE 2 binding and reactivity with RBM targeted antibodies viz., B38, BD23, CB6, P2B-F26 and EY6A suggests that variant have relatively higher affinity with ACE 2 receptor which may support higher infectivity. The study warrants large scale monitoring of Indian isolates as SARS-CoV-2 virus is expected to evolve and mutations may appear in unpredictable way.

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