Phytochemicals as Therapeutics Against COVID-19: An In-Silico Study

Since December 2019, the worldwide spread of COVID-19 has brought the majority of the world to a standstill, affecting daily lives as well as economy. Under these conditions, it is imperative to develop a cure as soon as possible. On account of some of the adverse side effects of the existing conventional drugs, researchers all around the world are screening natural antiviral phytochemicals as potential therapeutic agents against COVID-19. This paper aims to review interactions of some specific phytochemicals with the receptor binding domain (RBD) of the Spike glycoprotein of SARS-CoV-2 and suggest their possible therapeutic applications. Literature search was done based on the wide array of in-silico studies conducted using broad spectrum phytochemicals against SARS-CoV-2 and other viruses. We shortlisted 26 such phytochemicals specifically targeting the S protein and its interactions with host receptors. To validate the previously published results, we also conducted molecular docking using the AutoDockVina application and identified 6 high potential phytochemicals for therapeutic use based on their binding energies. Besides this, availability of these compounds, their mode of action, toxicity data and cost-effectiveness were also taken into consideration. Our review specifically identifies 6 phytochemicals that can be used as potential treatments for COVID-19 based on their availability, toxicology results and low costs of production. However, all these compounds need to be further validated by wet lab experiments and should be approved for clinical use only after appropriate trials.

Download Full-text

In silico Analysis of Phylogeny and Virulence Genes in STEC Strains Associated with Outbreaks

Türk Mikrobiyoloji Cemiyeti Dergisi ◽

10.5222/tmcd.2021.07769 ◽

2021 ◽

Author(s):

Mehmet Demirci ◽

Akın Yiğin ◽

Fadile Yıldız Zeyrek

Keyword(s):

Foodborne Pathogens ◽

In Silico ◽

Virulence Genes ◽

Genomic Analysis ◽

In Silico Analysis ◽

Comparative Genomic ◽

Phylogeny Analysis ◽

In Silico Study ◽

The World ◽

Different Parts

Objective: Shiga toxin-producing E. coli (STEC) strains are important foodborne pathogens. Significant outbreaks with STEC strains can be encountered, even if the geography, time or resources were different. The aim of our in silico study was to compare the virulance factors and phylogeny of STEC strains such as EDL933 and Sakai, which have been identified as an agent in important outbreaks in different parts of the world and whole genomic data were in open databases. Method: Genomic NCBI data of eight strains were included in our study, including seven different STEC strains associated with significant epidemics in different parts of the world, and one supershedder strain obtained from cattle feces. Results: According to phylogeny analysis, the most similar strain to EDL933 strain was TW14588, with 96.4% similarity. The most distant similarity was Sakai strains with 79.2%. According to the virulence genes analysis; the presence of 333 genes that constitute virulence factors under nine headings were detected. In the first STEC origin, EDL933, 45% of all virulence genes were found to be active. Adherence genes such as Ecp, Elf, Hcp and toxin genes such as clyA were active in all strains except stx genes. Conclusion: In our in silico study of comparative genomic analysis of STEC strains which are associated with outbreaks, it was determined that STEC strains used different virulence genes besides the stx gene. Indeed, they used certain virulence genes, even their sources, time and locations were different, in the pathogenesis

Download Full-text

An in silico structural insights into Plasmodium LytB protein and its inhibition

Acta Crystallographica Section A Foundations and Advances ◽

10.1107/s2053273314082096 ◽

2014 ◽

Vol 70 (a1) ◽

pp. C1791-C1791

Author(s):

Rajabrata Bhunya ◽

Suman Nandy ◽

Alpana Seal

Keyword(s):

In Silico ◽

3D Structure ◽

Three Dimensional ◽

Comparative Modeling ◽

Binding Energies ◽

E Coli ◽

Dimethylallyl Diphosphate ◽

In Silico Study ◽

Structural Insights ◽

Insight Into

In most of the pathogenic organisms including Plasmodium falciparum, isoprenoids are synthesized via MEP (MethylErythritol 4-Phosphate) pathway. LytB is the last enzyme of this pathway which catalyzes the conversion of (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate (HMBPP) into the two isoprenoid precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Since the MEP pathway is not used by humans, it represents an attractive target for the development of new antimalarial compounds or inhibitors. Here a systematic in-silico study has been conducted to get an insight into the structure of Plasmodium lytB as well as its affinities towards different inhibitors. We used comparative modeling technique to predict the three dimensional (3D) structure of Plasmodium LytB taking E. Coli LytB protein (PDB ID: 3KE8) as template and the model was subsequently refined through molecular dynamics (MD) simulation. A large ligand dataset containing diphospate group was subjected for virtual screening against the target using GOLD 5.2 program. Considering the mode of binding and affinities, 17 leads were selected on basis of binding energies in comparison to its substrate HMBPP (Gold.Chemscore.DG: -20.9734 kcal/mol). Among them, 5 were discarded because of their inhibitory activity towards other human enzymes. The rest 12 potential leads carry all the properties of any "drug like" molecule and the knowledge of Plasmodium LytB inhibitory mechanism which can provide valuable support for the antimalarial inhibitor design in future.

Download Full-text

THE POTENTIAL OF ROBUSTA COFFEE (COFFEA CANEPHORA) AS A COLORECTAL CANCER THERAPY MODALITY: AN IN SILICO STUDY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2021.v14i10.43025 ◽

2021 ◽

pp. 83-87

Author(s):

DESSY AGUSTINI ◽

LEO VERNADESLY ◽

DELVIANA ◽

THEODORUS

Keyword(s):

Colorectal Cancer ◽

In Silico ◽

Hydrophobic Interactions ◽

Binding Energies ◽

In Vivo Studies ◽

Discovery Studio ◽

Robusta Coffee ◽

In Silico Study

Objectives: This research aims to determine the efficacy of compounds in robusta coffee against colorectal cancer through the inhibition of the T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) receptor. Methods: This in silico study has been conducted in computing platform from June to August 2021. The selected test compounds would go through the Lipinski rule screening through the SwissADME website and the compounds that met these regulations would be docked to the TIGIT protein using AutoDock Tools and AutoDock Vina. The interactions with the highest binding energies were visualized using BIOVIA Discovery Studio 2020. The test compounds then underwent a toxicity profile analysis on the admetSAR 2.0 website. Results: All test compounds complied with the Lipinski rule. The molecular docking results showed the highest binding energy in kahweol and cafestol (−8.1 kcal/mol) compared to OMC (−7.9 kcal/mol), chlorogenic acid (−7.8 kcal/mol), caffeic acid (−6.3 kcal/mol), caffeine (−6.1 kcal/mol), trigonelline (−5.3 kcal/mol), HMF (−5.1 kcal/mol), furfuryl alcohol (−4.4 kcal/mol), and 5-fluorouracil as the comparator drug (−5.3 kcal/mol). Kahweol, cafestol, and 5-fluorouracil revealed the hydrophobic interactions and hydrogen bonds with amino acid residues in TIGIT. Kahweol and cafestol unveiled minimal toxicity prediction Conclusion: Kahweol and cafestol demonstrated the best results in inhibiting the TIGIT protein which played a role in colorectal cancer. In vitro and in vivo studies are needed to strengthen the findings of this research.

Download Full-text

Interaction of drugs candidates with various SARS-CoV-2 receptors: an in silico study to combat COVID-19

10.26434/chemrxiv.12100968 ◽

2020 ◽

Author(s):

Romulo O. Barros ◽

Fabio L. C. C. Junior ◽

Wildrimak S. Pereira ◽

Neiva M. N. Oliveira ◽

Ricardo Ramos

Keyword(s):

Molecular Docking ◽

In Silico ◽

Social Health ◽

Research Institutions ◽

Health Measures ◽

In Silico Study ◽

The World ◽

Anti Hiv ◽

Society Research

The world is currently facing the COVID-19 pandemic caused by the SARS-CoV-2 virus. The pandemic is causing the death of people around the world and public and social health measures to slow or prevent the spread of COVID-19 are being implemented with the involvement of all members of society. Research institutions are accelerating the discovery of vaccines and therapies for the COVID-19. In this work, molecular docking was used to study (in silico) the interaction of twenty-four ligands, divided into four groups, with four important SARS-CoV-2 receptors. The results showed that Metaquine (group 01), antimalarial substance and the anti-HIV antiretroviral Saquinavir (group 03), presented interaction with all the studied receptors, indicating that they are potentials candidates for muti-target drugs for COVID-19.

Download Full-text

In Silico Drug Discovery of 4-Hyroxypanduratin A, 6-Gingerol and Luteolin Targeting Nipah Virus

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i46b32964 ◽

2021 ◽

pp. 477-484

Author(s):

Anurag Verma ◽

Piyush Mittal ◽

Milind S. Pande ◽

Neelanchal Trivedi

Keyword(s):

Fusion Protein ◽

In Silico ◽

Virus Entry ◽

Nipah Virus ◽

Binding Energies ◽

Viral Agent ◽

In Silico Studies ◽

Viral Target ◽

Dietary Food

Nipah Virus is a zoo tonic virus and has re-emerged again with more deadliness. NiV has infected many animals and humans worldwide and a huge loss to life has been faced. NiV contains a Fusion protein on its outer membrane which helps in the virus entry into the host cell. This fusion protein is a virulent factor and is a major anti-viral target. Many medicinal plants have been used against viral diseases, current research aims towards the potential of three daily dietary food elements that can be used as an anti-viral agent. In-silico studies are performed with 4-hyroxypanduratin A, 6-gingerol and Luteolin against the NiV-F and binding energies were calculated. It was reported that these phyto-compounds have good negative binding energies and they have the promising potential against Nipah Virus. Further in-vitro research can be performed with these phyto-compounds to design a specific drug against Nipah Virus.

Download Full-text

In Silico Studies of Tumor Targeted Peptide-Conjugated Natural Products for Targeting Over-Expressed Receptors in Breast Cancer Cells Using Molecular Docking, Molecular Dynamics and MMGBSA Calculations

Applied Sciences ◽

10.3390/app12010515 ◽

2022 ◽

Vol 12 (1) ◽

pp. 515

Author(s):

Lucy R. Hart ◽

Charlotta G. Lebedenko ◽

Saige M. Mitchell ◽

Rachel E. Daso ◽

Ipsita A. Banerjee

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

In Silico ◽

Point Mutations ◽

Binding Energies ◽

Peptide Sequence ◽

Peroxisome Proliferator ◽

Peptide Conjugates ◽

Biological Studies ◽

In Silico Studies

In this work, in silico studies were carried out for the design of diterpene and polyphenol-peptide conjugates to potentially target over-expressed breast tumor cell receptors. Four point mutations were induced into the known tumor-targeting peptide sequence YHWYGYTPQN at positions 1, 2, 8 and 10, resulting in four mutated peptides. Each peptide was separately conjugated with either chlorogenate, carnosate, gallate, or rosmarinate given their known anti-tumor activities, creating dual targeting compounds. Molecular docking studies were conducted with the epidermal growth factor receptor (EGFR), to which the original peptide sequence is known to bind, as well as the estrogen receptor (ERα) and peroxisome proliferator-activated receptor (PPARα) using both Autodock Vina and FireDock. Based on docking results, peptide conjugates and peptides were selected and subjected to molecular dynamics simulations. MMGBSA calculations were used to further probe the binding energies. ADME studies revealed that the compounds were not CYP substrates, though most were Pgp substrates. Additionally, most of the peptides and conjugates showed MDCK permeability. Our results indicated that several of the peptide conjugates enhanced binding interactions with the receptors and resulted in stable receptor-ligand complexes; Furthermore, they may successfully target ERα and PPARα in addition to EGFR and may be further explored for synthesis and biological studies for therapeutic applications.

Download Full-text

The Potency of Catechin from Gambir (Uncaria gambir Roxb.) as a Natural Inhibitor of MurA (1UAE) Enzyme: In vitro and In silico studies

Letters in Drug Design & Discovery ◽

10.2174/1570180817999200714104737 ◽

2020 ◽

Vol 17 (12) ◽

pp. 1531-1537

Author(s):

Bella Riyana ◽

Desi Harneti Putri Huspa ◽

Mieke Hemiawati Satari ◽

Dikdik Kurnia

Keyword(s):

Cell Wall ◽

Bacterial Cell ◽

In Silico ◽

Bacterial Activity ◽

Bacterial Cell Wall ◽

Resistant Bacteria ◽

In Silico Studies ◽

In Silico Study ◽

Natural Inhibitor

Background: Currently, infectious diseases caused by pathogenic and resistant bacteria are more challenging for anti-bacterial drug discovery. The discovery of new anti-bacterial agents developed in many mechanisms includes disruption of the bacterial cell wall formations. The MurA is a key enzyme contributing to the first step of bacterial peptidoglycan biosynthesis and is, therefore, proposed as an effective bactericidal target. Objective: The purpose of this research is to identify anti-bacterial compounds from U. gambir Roxb and to predict the potential inhibitory activities against murA enzyme by in silico study. Materials and Methods: Investigation and discovery of new inhibitors of MurA enzyme were conducted on the medicinal plant of Gambir (Uncaria gambir Roxb) and those that reportedly contained anti-bacterial agents. The anti-bacterial compounds were isolated by combinations of chromatography methods guided by anti-bacterial activity against bacteria of E. faecalis, S. mutans, and S. sanguinis. The structures of active compounds were characterized by spectroscopic methods, and the anti-bacterial activity was evaluated by the microdilution method (in vitro) combined with molecular docking of the MurA enzyme (in silico). Results: The anti-bacterial flavonoids of catechin were isolated from U. gambir Roxb with MIC values of 6250 and 12500 ppm, respectively, against S. sanguinis and E. faecalis. The in silico study showed that catechin has a binding affinity of -8.5 Kcal/mol to MurA which is higher than fosfomycin as a positive control. Conclusions: The catechin is predicted to have potential as a new natural inhibitor of the MurA enzyme to inhibit bacterial cell wall biosynthesis.

Download Full-text

Multi-Target Drugs Against Metabolic Disorders

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666181217123357 ◽

2019 ◽

Vol 19 (4) ◽

pp. 402-418 ◽

Cited By ~ 3

Author(s):

Luciana Scotti ◽

Alex France Messias Monteiro ◽

Jéssika de Oliveira Viana ◽

Francisco Jaime Bezerra Mendonça Junior ◽

Hamilton M. Ishiki ◽

...

Keyword(s):

In Silico ◽

Metabolic Disorders ◽

The Body ◽

Target Drug ◽

Body Tissues ◽

In Silico Studies ◽

Hybrid Molecules ◽

In Silico Study ◽

Diabetes And Obesity ◽

New Strategies

Background: Metabolic disorders are a major cause of illness and death worldwide. Metabolism is the process by which the body makes energy from proteins, carbohydrates, and fats; chemically breaking these down in the digestive system towards sugars and acids which constitute the human body's fuel for immediate use, or to store in body tissues, such as the liver, muscles, and body fat. Objective: The efficiency of treatments for multifactor diseases has not been proved. It is accepted that to manage multifactor diseases, simultaneous modulation of multiple targets is required leading to the development of new strategies for discovery and development of drugs against metabolic disorders. Methods: In silico studies are increasingly being applied by researchers due to reductions in time and costs for new prototype synthesis; obtaining substances that present better therapeutic profiles. Discussion: In the present work, in addition to discussing multi-target drug discovery and the contributions of in silico studies to rational bioactive planning against metabolic disorders such as diabetes and obesity, we review various in silico study contributions to the fight against human metabolic pathologies. Conclusion: In this review, we have presented various studies involved in the treatment of metabolic disorders; attempting to obtain hybrid molecules with pharmacological activity against various targets and expanding biological activity by using different mechanisms of action to treat a single pathology.

Download Full-text

Severe Acute Respiratory Syndrome Coronavirus-2 Emergence and Its Treatment with Alternative Medicines: A Review

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00967 ◽

2021 ◽

pp. 5551-5557

Author(s):

Arif Nur Muhammad Ansori ◽

Viol Dhea Kharisma ◽

Amaq Fadholly ◽

Martia Rani Tacharina ◽

Yulanda Antonius ◽

...

Keyword(s):

In Silico ◽

Natural Compound ◽

Specific Treatment ◽

In Silico Screening ◽

Transmitted Infection ◽

Positive Effects ◽

Alternative Medicines ◽

In Silico Studies ◽

The World ◽

Phytochemical Compounds

Known as the causal factor of the recent global COVID-19 pandemic, any SARS-CoV-2 is not the only coronavirus that has constituted a menace to society and taken thousands of human lives. Two previous pandemics were also led by coronaviruses; such as the MERS-CoV in 2012 and another SARS-CoV in 2002. Only five months into existence, SARS-CoV-2 transmitted infection to approximately 75 million people and it has led to more than 1.5 million of deaths all over the world. Unfortunately, there has not been any specific treatment yet for COVID-19 yet and its control is purely empirical. The examinations of the parity between SARS-CoV-2 and SARS-CoV, in terms of their genomics, origin, epidemiology, and pathogenesis, suggested that we may use the previous data of MERS-CoV or SARS-CoV as a guideline for uncovering the effective approach to strive against SARS-CoV-2. Various studies have reported the positive effects of numerous phytochemical compounds against SARS-CoV and MERS-CoV. Interestingly, this idea has been emplyed for SARS-CoV-2, and in silico screening of phytochemical compounds has been performed for identifying the potential candidates for COVID-19 treatment. Curcumin is an example of a natural compound which was demonstrated as potent candidate contrary to SARS-CoV-2 protease derived from the in silico studies. Herein, the occurrence of SARS-CoV-2 and the aplication of alternative medicines for treating coronavirus diseases are briefly reviewed.

Download Full-text