scholarly journals Inhibitory Effect of Phytochemicals from Azadirachta indica A Juss. and Tinospora cordifolia (Thunb.) Miers against SARS-CoV-2 Mpro and Spike Protease- An In Silico Analysis

2020 ◽  
Author(s):  
RAMAKRISHNAMACHARYA CH ◽  
VANITHA MURALIKUMAR ◽  
CHANDRASEKAR S
Keyword(s):  
Medicinal Plants ◽  
Azadirachta Indica ◽  
In Silico ◽  
Viral Infections ◽  
In Silico Analysis ◽  
Inhibitory Effect ◽  
Tinospora Cordifolia ◽  
Autodock Vina ◽  
Reference Drug ◽  
Silico Analysis

Abstract COVID 19 caused by SARS-CoV-2 is spreading worldwide and affected 10 million people with a mortality rate between 0.5 % to 5%. Medicinal plants from China, Morocco, Algeria, Africa and India were tested for antiviral efficacy in SARS-CoV-2. Ayurveda Medicine described many medicinal plants. The Nimba (Azadirachta indica A. Juss) is used in fever, bacterial and viral infections, and Amrita (Tinospora cordifolia (Thunb.) Miers) is used as antiviral, antipyretic, and anti-inflammatory purposes. The combination of both these plants is called Nimbamritam, and it is widely used in pyrexia, dermatitis, viral infections, etc. Spike protease (PDB ID 6VXX) and Mpro (PDB ID 6LU) were retrieved from RCSB and 16 ligands from A. indica and 6 ligands from T. cordifolia were obtained from IMPPAT and PubChem. AutoDock Vina embedded PyRx was used for docking. Remdesivir was taken as a reference drug. In silico study of Cordifolide A of T cordifolia showed the highest scores with -8.2 Kcal/mol and -10.3Kcal/mol with Mpro protease and Spike protease respectively. Cordifolide A had 4 H bonds and Kaempferol had 7 non-conventional bonds, including van der Waal with Mpro (6LU7) protease. The interactions with 6VXX had 5 H bonds in each ligand Cordifolide A and Azadirachtin B. The prevention of virus entry by targeting spike protease host receptor ACE2 and restricting replication of the viral genome by targeting Mpro residues were identified in our study. A. indica and T. cordifolia are promising therapeutic agents in COVID 19.

scholarly journals Inhibitory Effect of Phytochemicals from Azadirachta indica A Juss. and Tinospora cordifolia (Thunb.) Miers against SARS-CoV-2 M pro and Spike Protease- An In Silico Analysis

2020 ◽  
Author(s):  
RAMÀKRISHNAMACHARYA CH ◽  
VANITHA MURALIKUMAR ◽  
CHANDRASEKAR SESHACHALAM
Keyword(s):  
Medicinal Plants ◽  
Azadirachta Indica ◽  
In Silico ◽  
Viral Infections ◽  
In Silico Analysis ◽  
Inhibitory Effect ◽  
Tinospora Cordifolia ◽  
Reference Drug ◽  
In Silico Study ◽  
Silico Analysis

COVID 19 caused by SARS-CoV-2 is spreading worldwide and affected 10 million people with a mortality rate between 0.5 % to 5%. Medicinal plants from China, Morocco, Algeria, Africa and India were tested for antiviral efficacy in SARS-CoV-2. Ayurveda Medicine described many medicinal plants. The Nimba ( Azadirachta indica A. Juss) is used in fever, bacterial and viral infections, and Amrita ( Tinospora cordifolia (Thunb.) Miers) is used as antiviral, antipyretic, and anti-inflammatory purposes. The combination of both these plants is called Nimbamritam, and it is widely used in pyrexia, dermatitis, viral infections, etc. Spike protease (PDB ID 6VXX) and M pro (PDB ID 6LU) were retrieved from RCSB and 16 ligands from A. indica and 6 ligands from T. cordifolia were obtained from IMPPAT and PubChem. AutoDock Vina embedded PyRx was used for docking. Remdesivir was taken as a reference drug. In silico study of Cordifolide A of T cordifolia showed the highest scores with -8.2 Kcal/mol and -10.3Kcal/mol with M pro protease and Spike protease respectively. Cordifolide A had 4 H bonds and Kaempferol had 7 non-conventional bonds, including van der Waal with M pro (6LU7) protease. The interactions with 6VXX had 5 H bonds in each ligand Cordifolide A and Azadirachtin B. The prevention of virus entry by targeting spike protease host receptor ACE2 and restricting replication of the viral genome by targeting M pro residues were identified in our study. A. indica and T. cordifolia are promising therapeutic agents in COVID 19.

scholarly journals In silico analysis of the supposed absence of therapeutic synergism in the association of hydroxychloroquine and azithromycin in COVID-19

2020 ◽  
Vol 9 (11) ◽  
pp. e2249119712
Author(s):  
Bruna Fernandes ◽  
Luan Gabriel Pinto ◽  
Ériky Fernandes Guimarães Silva ◽  
Angélica De Fátima Marcussi ◽  
Anderson Dillmann Groto ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Autodock Vina ◽  
Silico Analysis

A associação terapêutica entre hidroxicloroquina (HCQ) e azitromicina (AZI) foi considerada como terapia para COVID-19, no entanto, não está claro se ocorre uma ação sinérgica. Para melhor compreender esta associação terapêutica, este estudo teve como objetivo analisar a interação do HCQ e AZI com receptores humanos in silico.. A análise foi realizada por simulação de docking molecular. As interações químicas do HCQ e AZI com prováveis ​​receptores no organismo humano, ACE2 e CD147, foram analisadas no software AutoDock Vina e os resultados analisados ​​no software PyMol. Os conformadores HCQ-ACE2 e AZI-CD147 foram formados com energia de afinidade significativa de -7,0 Kcal / mol e -7,8 Kcal / mol, respectivamente. Apesar da interação entre HCQ e ACE2 poder prevenir a invasão das células pelo vírus, essa interação pode levar a efeitos colaterais graves. Por sua vez, a interação AZI-CD147 também pode atuar impedindo a entrada do vírus nas células. Além disso, de acordo com o in silicodados, a interação AZI-CD147 ocorreria de forma mais eficaz, o que leva a crer que a ação terapêutica do HCQ no COVID-19 não é tão relevante quanto a ação do AZI e não haveria sinergismo.

scholarly journals Cholinesterase-inhibitory effect and in silico analysis of alkaloids from bulbs of Hieronymiella species

Phytomedicine ◽  
2018 ◽  
Vol 39 ◽  
pp. 66-74 ◽  
Author(s):  
Javier E. Ortiz ◽  
Adriana Garro ◽  
Natalia B. Pigni ◽  
María Belén Agüero ◽  
German Roitman ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Inhibitory Effect ◽  
Silico Analysis

scholarly journals In Silico Analysis of Compounds Isolated from Selected Indian Medicinal Plants against Chikungunya Viral Proteins

2020 ◽  
Vol 82 (4) ◽  
Author(s):  
LAXMI MISHRA ◽  
KAVERI TYAGI ◽  
MANISHA KUMARI ◽  
SHRUTI KHANNA ◽  
JUPITA HANDIQUE ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
In Silico ◽  
In Silico Analysis ◽  
Viral Proteins ◽  
Indian Medicinal Plants ◽  
Silico Analysis

scholarly journals In silico analysis of phytoconstituents from Tinospora cordifolia with targets related to diabetes and obesity

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Bijendra K. Mandar ◽  
Pukar Khanal ◽  
B. M. Patil ◽  
Yadu Nandan Dey ◽  
Ismail Pasha
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Tinospora Cordifolia ◽  
Diabetes And Obesity ◽  
Silico Analysis

scholarly journals In Vitro Phenotypic Activity and In Silico Analysis of Natural Products from Brazilian Biodiversity on Trypanosoma cruzi

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5676
Author(s):  
Raiza B. Peres ◽  
Ludmila F. de A. Fiuza ◽  
Patrícia B. da Silva ◽  
Marcos M. Batista ◽  
Flávia da C. Camillo ◽  
...  
Keyword(s):  
Natural Products ◽  
Trypanosoma Cruzi ◽  
In Silico ◽  
In Silico Analysis ◽  
Mammalian Host ◽  
Reference Drug ◽  
Wide Range ◽  
Pure Compounds ◽  
Silico Analysis

Chagas disease (CD) affects more than 6 million people worldwide. The available treatment is far from ideal, creating a demand for new alternative therapies. Botanical diversity provides a wide range of novel potential therapeutic scaffolds. Presently, our aim was to evaluate the mammalian host toxicity and anti-Trypanosoma cruzi activity of botanic natural products including extracts, fractions and purified compounds obtained from Brazilian flora. In this study, 36 samples of extracts and fractions and eight pure compounds obtained from seven plant species were evaluated. The fraction dichloromethane from Aureliana fasciculata var. fasciculata (AFfPD) and the crude extract of Piper tectoniifolium (PTFrE) showed promising trypanosomicidal activity. AFfPD and PTFrE presented EC50 values 10.7 ± 2.8 μg/mL and 12.85 ± 1.52 μg/mL against intracellular forms (Tulahuen strain), respectively. Additionally, both were active upon bloodstream trypomastigotes (Y strain), exhibiting EC50 2.2 ± 1.0 μg/mL and 38.8 ± 2.1 μg/mL for AFfPD and PTFrE, respectively. Importantly, AFfPD is about five-fold more potent than Benznidazole (Bz), the reference drug for CD, also reaching lower EC90 value (7.92 ± 2.2 μg/mL) as compared to Bz (23.3 ± 0.6 μg/mL). Besides, anti-parasitic effect of eight purified botanic substances was also investigated. Aurelianolide A and B (compounds 1 and 2) from A. fasciculata and compound 8 from P. tuberculatum displayed the best trypanosomicidal effect. Compounds 1, 2 and 8 showed EC50 of 4.6 ± 1.3 μM, 1.6 ± 0.4 μM and 8.1 ± 0.9 μM, respectively against intracellular forms. In addition, in silico analysis of these three biomolecules was performed to predict parameters of absorption, distribution, metabolism and excretion. The studied compounds presented similar ADMET profile as Bz, without presenting mutagenicity and hepatotoxicity aspects as predicted for Bz. Our findings indicate that these natural products have promising anti-T. cruzi effect and may represent new scaffolds for future lead optimization.

scholarly journals Synthesis of new thiazolo[3,2-a]pyrimidine derivatives and in silico analysis of their bioactivity

2021 ◽  
Vol 57 (4) ◽  
pp. 456-462
Author(s):  
I. V. Mineeva ◽  
Y. V. Faletrov ◽  
V. A. Starovoytova ◽  
V. M. Shkumatov
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Lipid Bilayer ◽  
In Silico ◽  
Cytochromes P450 ◽  
In Silico Analysis ◽  
Autodock Vina ◽  
Pyrimidine Derivatives ◽  
Silico Analysis

An effective method of synthesis thiazolo[3,2-a]pyrimidine derivatives was developed and the compounds with n-pentyl or β-acetoxycyclopropyl as well as fluorescent benzo[f]coumarin substituents were obtained with yields 60 % and more. Using computational (in silico) approaches we demonstrated the ability of the obtained compounds to permeate lipid bilayer as well as their affinity to some protein kinases (compounds 4 and 6 bind with a protein kinase AKT1 with PDB code 3о96; Autodock Vina-computed energy of binding (Ebind) values were -10.9 and -10.6 kcal/mol, respectively), acethylcholine esterase and some human cytochromes P450 (for P450 3A4, pdb 5vcd, Ebind -12.3 kcal/mol).

scholarly journals SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites

2021 ◽  
Vol 22 (16) ◽  
pp. 9035
Author(s):  
Guilherme C. Lechuga ◽  
Franklin Souza-Silva ◽  
Carolina Q. Sacramento ◽  
Monique R. O. Trugilho ◽  
Richard H. Valente ◽  
...  
Keyword(s):  
In Silico ◽  
Plaque Assay ◽  
In Silico Analysis ◽  
Inhibitory Effect ◽  
Parallel Synthesis ◽  
Affinity Column ◽  
Binding Motifs ◽  
N Protein ◽  
Column Adsorption ◽  
Silico Analysis

(1) Background: coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been linked to hematological dysfunctions, but there are little experimental data that explain this. Spike (S) and Nucleoprotein (N) proteins have been putatively associated with these dysfunctions. In this work, we analyzed the recruitment of hemoglobin (Hb) and other metabolites (hemin and protoporphyrin IX-PpIX) by SARS-Cov2 proteins using different approaches. (2) Methods: shotgun proteomics (LC–MS/MS) after affinity column adsorption identified hemin-binding SARS-CoV-2 proteins. The parallel synthesis of the peptides technique was used to study the interaction of the receptor bind domain (RBD) and N-terminal domain (NTD) of the S protein with Hb and in silico analysis to identify the binding motifs of the N protein. The plaque assay was used to investigate the inhibitory effect of Hb and the metabolites hemin and PpIX on virus adsorption and replication in Vero cells. (3) Results: the proteomic analysis by LC–MS/MS identified the S, N, M, Nsp3, and Nsp7 as putative hemin-binding proteins. Six short sequences in the RBD and 11 in the NTD of the spike were identified by microarray of peptides to interact with Hb and tree motifs in the N protein by in silico analysis to bind with heme. An inhibitory effect in vitro of Hb, hemin, and PpIX at different levels was observed. Strikingly, free Hb at 1mM suppressed viral replication (99%), and its interaction with SARS-CoV-2 was localized into the RBD region of the spike protein. (4) Conclusions: in this study, we identified that (at least) five proteins (S, N, M, Nsp3, and Nsp7) of SARS-CoV-2 recruit Hb/metabolites. The motifs of the RDB of SARS-CoV-2 spike, which binds Hb, and the sites of the heme bind-N protein were disclosed. In addition, these compounds and PpIX block the virus’s adsorption and replication. Furthermore, we also identified heme-binding motifs and interaction with hemin in N protein and other structural (S and M) and non-structural (Nsp3 and Nsp7) proteins.

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