Indian Ethnomedicinal Phytochemicals as Promising Inhibitors of RNA-Binding Domain of SARS-CoV-2 Nucleocapsid Phosphoprotein: An In Silico Study

SARS-CoV-2, an etiological agent of COVID-19, has been the reason for the unexpected global pandemic, causing severe mortality and imposing devastative effects on public health. Despite extensive research work put forward by scientist around globe, so far, no suitable drug or vaccine (safe, affordable, and efficacious) has been identified to treat SARS-CoV-2. As an alternative way of improvising the COVID-19 treatment strategy, that is, strengthening of host immune system, a great deal of attention has been given to phytocompounds from medicinal herbs worldwide. In a similar fashion, the present study deliberately focuses on the phytochemicals of three Indian herbal medicinal plants viz., Mentha arvensis, Coriandrum sativum, and Ocimum sanctum for their efficacy to target well-recognized viral receptor protein through molecular docking and dynamic analyses. Nucleocapsid phosphoprotein (N) of SARS-CoV-2, being a pivotal player in replication, transcription, and viral genome assembly, has been recognized as one of the most attractive viral receptor protein targets for controlling the viral multiplication in the host. Out of 127 phytochemicals screened, nine (linarin, eudesmol, cadinene, geranyl acetate, alpha-thujene, germacrene A, kaempferol-3-O-glucuronide, kaempferide, and baicalin) were found to be phenomenal in terms of exhibiting high binding affinity toward the catalytic pocket of target N-protein. Further, the ADMET prediction analysis unveiled the non-tumorigenic, noncarcinogenic, nontoxic, non-mutagenic, and nonreproductive nature of the identified bioactive molecules. Furthermore, the data of molecular dynamic simulation validated the conformational and dynamic stability of the docked complexes. Concomitantly, the data of the present study validated the anti-COVID efficacy of the bioactives from selected medicinal plants of Indian origin.

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Green Synthesis of Silver Nanoparticles Using Olden-landia corymbosa and Ocimum sanctum Leaf Aqueous Extract

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2020.13.3.11 ◽

2020 ◽

Vol 13 (3) ◽

pp. 4959-4964

Author(s):

Prof.(Dr.) Sirshendu Chatterjee Chatterjee ◽

Shaktijit Das ◽

Moumita Saha ◽

Pranabesh Ghosh ◽

Titav Sengupta ◽

...

Keyword(s):

Medicinal Plants ◽

Green Synthesis ◽

Aqueous Extract ◽

Nano Particles ◽

Bioactive Molecules ◽

Primary Amines ◽

Ocimum Sanctum ◽

Leaf Aqueous Extract ◽

Vis Spectroscopy ◽

Ft Ir

The field of nanotechnology is the most renowned area of research in modern day science. One of the most convenient and comprehensive technique related to the synthesis of nanoparticles using plant extracts and their subsequent action. On the other hand, herbal medicines become an integral part of modern-day treatment strategy around the globe; combination of these two ways are widely accepted and beneficial due to its low cost, better societal recognition and less side effects. Phytochemical analysis revealed that leaf aqueous extract of two medicinal plants Oldenlandia corymbosa and Ocimum sanctum, harbours high concentration of antioxidants and bioactive molecules. Hence our present course of study aims at the green synthesis of silver nano-conjugates using Oldenlandia corymbosa and Ocimum sanctum leaf aqueous extracts. The synthesized nano-conjugates have undergone advanced chara-cterization techniques including UV-Vis Spectro-photometry, DLS, and FT-IR. The UV-Vis spectroscopy results showed single peak at 420 nm and 430 nm for Oldenlandia corymbosa and Ocimum sanctum nano-conjugates, respectively. The particle size for Oldenlandia corymbosa and Ocimum sanctum nano-particles are 21.04 nm and 24.36 nm, respectively as observed from the DLS data, and finally, the FT-IR data confirms the conjugation of bioactive molecules of the medicinal plants indicating that primary amines, secondary amines, alcohols, phenols, aldehydes, aliphatic amines, alkenes, functional groups of the bioactive molecules are responsible for the stability of prepared silver nano-conjugates

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In silico screening of hundred phytocompounds of ten medicinal plants as potential inhibitors of nucleocapsid phosphoprotein of COVID-19: An approach to prevent virus assembly

10.21203/rs.3.rs-30484/v1 ◽

2020 ◽

Author(s):

Rajan Rolta ◽

Rohitash Yadav ◽

Deeksha Salaria ◽

Anuradha Sourirajan ◽

Kamal Dev

Keyword(s):

Medicinal Plants ◽

Active Sites ◽

Rna Binding ◽

Virus Assembly ◽

Specific Treatment ◽

Binding Domain ◽

Binding Energies ◽

Receptor Protein ◽

Aloe Emodin ◽

Rna Binding Domain

Abstract Currently, there is no specific treatment to cure COVID-19. Many medicinal plants have antiviral, antioxidant, antibacterial, antifungal, anticancer, wound healing etc. Therefore, the aim of the current study was to screen for potent inhibitors of N-terminal domain (NTD) of nucleocapsid phosphoproteinof SARS-CoV-2. The structure of NTD of RNA binding domain of nucleocapsid phosphoprotein of SARS coronavirus 2 was retrieved from the Protein Data Bank (PDB 6VYO)and the structures of 100 different phytocompoundswere retrieved from Pubchem. The receptor protein and ligands were prepared using Schrodinger’s Protein Preparation Wizard. Molecular docking was done by using the Schrodinger’s maestro 12.0 software. Drug likeness and toxicity of active phytocompounds was predicted by using Swiss adme, admetSAR and protox II online servers. We have identified three potential active sites (named as A, B, C) on receptor protein for efficient binding of the phytocompounds. We found that, among 100 phytocompounds, emodin, aloe-emodin, anthrarufin, alizarine, and dantron of Rheum emodi showed good binding affinity at all the three active sites of RNA binding domain of nucleocapsid phosphoprotein of COVID-19.The binding energies of emodin, aloe-emodin, anthrarufin, alizarine, and dantron were -8.299 , -8.508, -8.456, -8.441, and -8.322 Kcal mol-1 respectively (site A), -7.714, -6.433, -6.354, -6.598, and -6.99 Kcal mol-1 respectively (site B), and -8.299, 8.508, 8.538, 8.841, and 8.322 Kcal mol-1 respectively (site C).All the active phytocompounds follows the drug likeness properties, non-carcinogenic, and non-toxic. Theses phytocompounds (alone or in combination) could be developed into effective therapy against COVID-19.

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SARS-CoV-2 N Protein Targets TRIM25-Mediated RIG-I Activation to Suppress Innate Immunity

Viruses ◽

10.3390/v13081439 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1439

Author(s):

Gianni Gori Savellini ◽

Gabriele Anichini ◽

Claudia Gandolfo ◽

Maria Grazia Cusi

Keyword(s):

Molecular Mechanisms ◽

Rna Binding ◽

Antagonistic Activity ◽

Binding Activity ◽

Host Immune System ◽

The Novel ◽

Protein Targets ◽

N Protein ◽

New Findings ◽

Severe Clinical Picture

A weak production of INF-β along with an exacerbated release of pro-inflammatory cytokines have been reported during infection by the novel SARS-CoV-2 virus. SARS-CoV-2 encodes several proteins able to counteract the host immune system, which is believed to be one of the most important features contributing to the viral pathogenesis and development of a severe clinical picture. Previous reports have demonstrated that SARS-CoV-2 N protein, along with some non-structural and accessory proteins, efficiently suppresses INF-β production by interacting with RIG-I, an important pattern recognition receptor (PRR) involved in the recognition of pathogen-derived molecules. In the present study, we better characterized the mechanism by which the SARS-CoV-2 N counteracts INF-β secretion and affects RIG-I signaling pathways. In detail, when the N protein was ectopically expressed, we noted a marked decrease in TRIM25-mediated RIG-I activation. The capability of the N protein to bind to, and probably mask, TRIM25 could be the consequence of its antagonistic activity. Furthermore, this interaction occurred at the SPRY domain of TRIM25, harboring the RNA-binding activity necessary for TRIM25 self-activation. Here, we describe new findings regarding the interplay between SARS-CoV-2 and the IFN system, filling some gaps for a better understanding of the molecular mechanisms affecting the innate immune response in COVID-19.

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Biochemical Composition, Antibacterial and Anti-Biofilm Activities of Indian Medicinal Plants

Anti-Infective Agents ◽

10.2174/2211352518999200622152308 ◽

2020 ◽

Vol 18 ◽

Author(s):

Mulugeta Mulat ◽

Fazlurrahman Khan ◽

Archana Pandita

Keyword(s):

Antibacterial Activity ◽

Medicinal Plants ◽

Pathogenic Bacteria ◽

Chemical Constituents ◽

Multidrug Resistant ◽

Chloroform Extract ◽

Acetone Extract ◽

Biologically Active ◽

Ocimum Sanctum ◽

Agar Disc

Background: Medicinal plants have been used for treatments of various health ailments and the practices as a remedial back to thousands of years. Currently, plant-derived compounds used as alternative ways of treatment for multidrug-resistant pathogens. Objective: In the present study, various parts of six medical plants such as Solanum nigrum, Azadirachta indica, Vitex negundo, Mentha arvensis, Gloriosa superba, and Ocimum sanctum were extracted for obtaining biological active constituents. Methods: Soxhlet method of extraction was used for obtaining crude extracts. Agar disc diffusion and 96-well plate spectroscopic reading were used to detect the extract’s antibacterial and antibiofilm properties. Results: The obtained extracts were tested for antimicrobial and antibiofilm properties at 25 mg/mL concentrations. Maximum antibacterial activity was observed in O. sanctum chloroform extract (TUCE) against Staphylococcus aureus (24.33±1.52 mm), S. nigrum acetone extract (MAAC) against Salmonella Typhimurium (12.6 ± 1.5 mm) and Pseudomonas aeruginosa (15.0 ±2.0 mm). Only TUCE exhibited antibacterial activity at least a minimum inhibitory concentration of 0.781 mg/mL. Better antibiofilm activities were also exhibited by petroleum extracts of G. superba (KAPE) and S. nigrum (MAPE) against Escherichia coli, S. Typhimurium, P. aeruginosa and S. aureus. Moreover, S. nigrum acetone extract (MAAC) and O. sanctum chloroform extract (TUCE) were showed anti-swarming activity with a reduction of motility 56.3% against P. aeruginosa and 37.2% against S. aureus. MAAC also inhibits Las A activity (63.3% reduction) in P. aeruginosa. Conclusion: Extracts of TUCE, MAAC, MAPE, and KAPE were exhibited antibacterial and antibiofilm properties against the Gram-positive and Gram-negative pathogenic bacteria. GCMS identified chemical constituents are responsible for being biologically active.

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Structure and Function of Major SARS-CoV-2 and SARS-CoV Proteins

Bioinformatics and Biology Insights ◽

10.1177/11779322211025876 ◽

2021 ◽

Vol 15 ◽

pp. 117793222110258

Author(s):

Ritesh Gorkhali ◽

Prashanna Koirala ◽

Sadikshya Rijal ◽

Ashmita Mainali ◽

Adesh Baral ◽

...

Keyword(s):

Genomic Organization ◽

Membrane Vesicles ◽

Structural Proteins ◽

Host Immune System ◽

Accessory Proteins ◽

Nonstructural Proteins ◽

N Protein ◽

Small Proteins ◽

Methylation Mark ◽

And Function

SARS-CoV-2 virus, the causative agent of COVID-19 pandemic, has a genomic organization consisting of 16 nonstructural proteins (nsps), 4 structural proteins, and 9 accessory proteins. Relative of SARS-CoV-2, SARS-CoV, has genomic organization, which is very similar. In this article, the function and structure of the proteins of SARS-CoV-2 and SARS-CoV are described in great detail. The nsps are expressed as a single or two polyproteins, which are then cleaved into individual proteins using two proteases of the virus, a chymotrypsin-like protease and a papain-like protease. The released proteins serve as centers of virus replication and transcription. Some of these nsps modulate the host’s translation and immune systems, while others help the virus evade the host immune system. Some of the nsps help form replication-transcription complex at double-membrane vesicles. Others, including one RNA-dependent RNA polymerase and one exonuclease, help in the polymerization of newly synthesized RNA of the virus and help minimize the mutation rate by proofreading. After synthesis of the viral RNA, it gets capped. The capping consists of adding GMP and a methylation mark, called cap 0 and additionally adding a methyl group to the terminal ribose called cap1. Capping is accomplished with the help of a helicase, which also helps remove a phosphate, two methyltransferases, and a scaffolding factor. Among the structural proteins, S protein forms the receptor of the virus, which latches on the angiotensin-converting enzyme 2 receptor of the host and N protein binds and protects the genomic RNA of the virus. The accessory proteins found in these viruses are small proteins with immune modulatory roles. Besides functions of these proteins, solved X-ray and cryogenic electron microscopy structures related to the function of the proteins along with comparisons to other coronavirus homologs have been described in the article. Finally, the rate of mutation of SARS-CoV-2 residues of the proteome during the 2020 pandemic has been described. Some proteins are mutated more often than other proteins, but the significance of these mutation rates is not fully understood.

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The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein

Nature Communications ◽

10.1038/s41467-020-20768-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Shan Lu ◽

Qiaozhen Ye ◽

Digvijay Singh ◽

Yong Cao ◽

Jolene K. Diedrich ◽

...

Keyword(s):

Phase Separation ◽

Potential Role ◽

Rna Binding ◽

Stress Granule ◽

M Protein ◽

Rich Region ◽

Virion Assembly ◽

N Protein ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions

AbstractThe multifunctional nucleocapsid (N) protein in SARS-CoV-2 binds the ~30 kb viral RNA genome to aid its packaging into the 80–90 nm membrane-enveloped virion. The N protein is composed of N-terminal RNA-binding and C-terminal dimerization domains that are flanked by three intrinsically disordered regions. Here we demonstrate that the N protein’s central disordered domain drives phase separation with RNA, and that phosphorylation of an adjacent serine/arginine rich region modulates the physical properties of the resulting condensates. In cells, N forms condensates that recruit the stress granule protein G3BP1, highlighting a potential role for N in G3BP1 sequestration and stress granule inhibition. The SARS-CoV-2 membrane (M) protein independently induces N protein phase separation, and three-component mixtures of N + M + RNA form condensates with mutually exclusive compartments containing N + M or N + RNA, including annular structures in which the M protein coats the outside of an N + RNA condensate. These findings support a model in which phase separation of the SARS-CoV-2 N protein contributes both to suppression of the G3BP1-dependent host immune response and to packaging genomic RNA during virion assembly.

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PR-1-Like Protein as a Potential Target for the Identification of Fusarium oxysporum: An In Silico Approach

BioTech ◽

10.3390/biotech10020008 ◽

2021 ◽

Vol 10 (2) ◽

pp. 8

Author(s):

Olalekan Olanrewaju Bakare ◽

Arun Gokul ◽

Marshall Keyster

Keyword(s):

Antimicrobial Peptides ◽

Fusarium Oxysporum ◽

In Silico ◽

Crop Yields ◽

Research Work ◽

Receptor Protein ◽

Economic Losses ◽

Protein Receptor ◽

Novel Biomarkers ◽

Docking Interaction

Fusarium oxysporum remains one of the leading causes of economic losses and poor crop yields; its detection is strained due to its presentation in various morphological and physiological forms. This research work sought to identify novel biomarkers for the detection of Fusarium oxysporum using in silico approaches. Experimentally validated anti-Fusarium oxysporum antimicrobial peptides (AMPs) were used to construct a profile against Fusarium oxysporum. The performance and physicochemical parameters of these peptides were predicted. The gene for the Fusarium oxysporum receptor protein PR-1-like Protein, Fpr1, was identified and translated. The resulting protein model from the translation was then validated. The anti-Fusarium oxysporum AMPs and Fusarium oxysporum receptor protein 3-D structures were characterized, and their docking interaction analyses were carried out. The HMMER in silico tool identified novel anti-Fusarium oxysporum antimicrobial peptides with good performance in terms of accuracy, sensitivity, and specificity. These AMPs also displayed good physicochemical properties and bound with greater affinity to Fusarium oxysporum protein receptor PR-1-like Protein. The tendency of these AMPs to precisely detect Fusarium oxysporum PR-1-like Protein, Fpr1, would justify their use for the identification of the fungus. This study would enhance and facilitate the identification of Fusarium oxysporum to reduce problems associated with poor crop yield, economic losses, and decreased nutritional values of plants to keep up with the growing population.

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Trimeric Hantavirus Nucleocapsid Protein Binds Specifically to the Viral RNA Panhandle

Journal of Virology ◽

10.1128/jvi.78.15.8281-8288.2004 ◽

2004 ◽

Vol 78 (15) ◽

pp. 8281-8288 ◽

Cited By ~ 53

Author(s):

M. A. Mir ◽

A. T. Panganiban

Keyword(s):

Nucleocapsid Protein ◽

Rna Binding ◽

Rna Viruses ◽

Sin Nombre Virus ◽

Viral Capsid ◽

Genomic Rna ◽

Rna Molecules ◽

N Protein ◽

High Affinity ◽

Negative Sense

ABSTRACT Hantaviruses are tripartite negative-sense RNA viruses and members of the Bunyaviridae family. The nucleocapsid (N) protein is encoded by the smallest of the three genome segments (S). N protein is the principal structural component of the viral capsid and is central to the hantavirus replication cycle. We examined intermolecular N-protein interaction and RNA binding by using bacterially expressed Sin Nombre virus N protein. N assembles into di- and trimeric forms. The mono- and dimeric forms exist transiently and assemble into a trimeric form. In contrast, the trimer is highly stable and does not efficiently disassemble into the mono- and dimeric forms. The purified N-protein trimer is able to discriminate between viral and nonviral RNA molecules and, interestingly, recognizes and binds with high affinity the panhandle structure composed of the 3′ and 5′ ends of the genomic RNA. In contrast, the mono- and dimeric forms of N bind RNA to form a complex that is semispecific and salt sensitive. We suggest that trimerization of N protein is a molecular switch to generate a protein complex that can discriminate between viral and nonviral RNA molecules during the early steps of the encapsidation process.

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Antiviral and Immunity-modulating Natural Herbs in the Prevention of COVID-19

Research Journal of Pharmacognosy and Phytochemistry ◽

10.52711/0975-4385.2021.00014 ◽

2021 ◽

pp. 81-94

Author(s):

Sonali S Gadge

Keyword(s):

Immune System ◽

Medicinal Plants ◽

Nigella Sativa ◽

Curcuma Longa ◽

Antiviral Drug ◽

Herbal Medicines ◽

Echinacea Purpurea ◽

Black Pepper ◽

Tinospora Cordifolia ◽

Ocimum Sanctum

The COVID-19 has spread all over the world and there is no single drug or medicine for the prevention and the treatment of this deadly disease. One can get prevention from this disease by boosting the immune system. Persons with weak immune system e.g. children, elder patients or patients with preexisting diseases affect rapidly due to coronavirus. This novel coronavirus attacks mainly on the person immunity. For the centuries the herbal medicinal plants have many beneficial effects against deadly viruses. Herbal medicines provide a rich resource for new antiviral drug development. These natural agents interact with the life cycle of virus such as virus entry, replication, assembly and release. In this review, the importance, immunomodulator, antiviral and pharmacological activities of some medicinal plants, namely, Allium Sativum, Zingiber Officinalis, Cinnamomum zeylanicum, Curcuma longa, Ocimum sanctum, Glycyrrhiza glabra, Ginseng, Black pepper, Emblica officinalis, Withania somnifera, Tinospora cordifolia, Echinacea purpurea, Azadirachta indica, Piper betel, Eugenia caryophyllata, Cinchona calisaya, Nigella sativa, Cuminum cyminum are highlighted. These medicinal plants have many phytoconstituents like alkaloids, glycosides, terpenoids, flavonoids, lactones, polysaccharides, volatile oils, tannins, resins, etc which are helpful for boosting immunity and will help in the prevention and in the management of COVID-19. Several types of research attempted to use herbal medicines against COVID-19.

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Recent Innovations of Organo-Fluorine synthesis and pharmacokinetics

Current Organic Chemistry ◽

10.2174/1385272825666210531111123 ◽

2021 ◽

Vol 25 ◽

Author(s):

Omkar Kamble ◽

Ramababu Dandela ◽

Sandip Shinde

Keyword(s):

Biological Activity ◽

Pharmacokinetic Study ◽

Fluorine Atom ◽

Neurological Diseases ◽

Research Work ◽

Chemical Properties ◽

Physical Property ◽

Bioactive Molecules ◽

Pharmacokinetic Property ◽

Research Areas

: The fluorinated compounds have significance in medicinal chemistry and pharmaceuticals research. The introduction of fluorine atom in the heterocyclic compounds increases biological activity, develops favourable physiochemical interaction. Combination of the heterocycles and fluorine substituent having large scope in the research work of the different drugs molecules. The compounds not only show biological activity but also show unique physical and chemical properties that open the doors of multidisciplinary research areas. Fluorine atom tolerance towards maximum functional groups, simplicity in operation, replacing hydrogen with fluorine of bioactive molecules are more efficient for the production at the commercial level. The fluorine substitution also increases the binding affinity to the targeted protein. Also, incorporation of fluorine into the drug helps to increase the polarity hence to increase the rate of drug metabolism and improves the metabolic stability. The pharmacokinetic study plays an important role in clinical research, since 1996, researcher Whitford discover that the pharmacokinetic of fluorine is depend on its pH and amount in the bone. pH of organofluoride governs the absorption, distribution and excretion of fluoride. It also increases the stability when binding with carbon atom and resulting in an increase in bioactivity. This is the main reason that around 25% of present active drugs on various diseases, including cancer, diabetes, HIV, etc. have fluorine as important content. Not only pharmacokinetic property but also the physical property of the drug can be enhanced or altered by selective insertion at the key place of the fluorine atom in the drug compound. In this report, we have summarized the interesting research article reported since 2000 for the synthesis of low fluorine substituted organic compounds for medicinal research and pharmacokinetic study of fluorine molecules in neurological diseases, cancer, and tuberculosis research.

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