scholarly journals Targeting novel coronavirus SARS-CoV-2 spike protein with phytoconstituents of Momordica charantia

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Santosh Kumar Singh ◽  
Shailesh Singh ◽  
Rajesh Singh
Keyword(s):  
Viral Infections ◽  
Hydrophobic Interactions ◽  
Docking Study ◽  
Docking Studies ◽  
Momordica Charantia ◽  
Spike Protein ◽  
Strong Interactions ◽  
Bitter Melon ◽  
Novel Coronavirus ◽  
Potential Interactions

Abstract Background Infections by the SARS-CoV-2 virus causing COVID-19 are presently a global emergency. The current vaccination effort may reduce the infection rate, but strain variants are emerging under selection pressure. Thus, there is an urgent need to find drugs that treat COVID-19 and save human lives. Hence, in this study, we identified phytoconstituents of an edible vegetable, Bitter melon (Momordica charantia), that affect the SARS-CoV-2 spike protein. Methods Components of Momordica charantia were tested to identify the compounds that bind to the SARS-CoV-2 spike protein. An MTiOpenScreen web-server was used to perform docking studies. The Lipinski rule was utilized to evaluate potential interactions between the drug and other target molecules. PyMol and Schrodinger software were used to identify the hydrophilic and hydrophobic interactions. Surface plasmon resonance (SPR) was employed to assess the interaction between an extract component (erythrodiol) and the spike protein. Results Our in-silico evaluations showed that phytoconstituents of Momordica charantia have a low binding energy range, -5.82 to -5.97 kcal/mol. A docking study revealed two sets of phytoconstituents that bind at the S1 and S2 domains of SARS-CoV-2. SPR showed that erythrodiol has a strong binding affinity (KD = 1.15 μM) with the S2 spike protein of SARS-CoV-2. Overall, docking, ADME properties, and SPR displayed strong interactions between phytoconstituents and the active site of the SARS-CoV-2 spike protein. Conclusion This study reveals that phytoconstituents from bitter melon are potential agents to treat SARS-CoV-2 viral infections due to their binding to spike proteins S1 and S2.

scholarly journals In Silico Identification and Docking-Based Drug Repurposing Against the Main Protease of SARS-CoV-2, Causative Agent of COVID-19

2020 ◽  
Author(s):  
Yogesh Kumar ◽  
Harvijay Singh
Keyword(s):  
Virtual Screening ◽  
Active Site ◽  
Viral Infections ◽  
Drug Repurposing ◽  
Docking Study ◽  
Docking Studies ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Approved Drugs

<div>The rapidly enlarging COVID-19 pandemic caused by novel SARS-coronavirus 2 is a global</div><div>public health emergency of unprecedented level. Therefore the need of a drug or vaccine that</div><div>counter SARS-CoV-2 is an utmost requirement at this time. Upon infection the ssRNA genome</div><div>of SARS-CoV-2 is translated into large polyprotein which further processed into different</div><div>nonstructural proteins to form viral replication complex by virtue of virus specific proteases:</div><div>main protease (3-CL protease) and papain protease. This indispensable function of main protease</div><div>in virus replication makes this enzyme a promising target for the development of inhibitors and</div><div>potential treatment therapy for novel coronavirus infection. The recently concluded α-ketoamide</div><div>ligand bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al.</div><div>has revealed the potential inhibitor binding mechanism and the determinants responsible for</div><div>involved molecular interactions. Here, we have carried out a virtual screening and molecular</div><div>docking study of FDA approved drugs primarily targeted for other viral infections, to investigate</div><div>their binding affinity in Mpro active site. Virtual screening has identified a number of antiviral</div><div>drugs, top ten of which on the basis of their bending energy score are further examined through </div><div>molecular docking with Mpro. Docking studies revealed that drug Lopinavir-Ritonavir, Tipranavir</div><div>and Raltegravir among others binds in the active site of the protease with similar or higher</div><div>affinity than the crystal bound inhibitor α-ketoamide. However, the in-vitro efficacies of the drug</div><div>molecules tested in this study, further needs to be corroborated by carrying out biochemical and</div><div>structural investigation. Moreover, this study advances the potential use of existing drugs to be</div><div>investigated and used to contain the rapidly expanding SARS-CoV-2 infection.</div>

scholarly journals In Silico Identification and Docking-Based Drug Repurposing Against the Main Protease of SARS-CoV-2, Causative Agent of COVID-19

2020 ◽  
Author(s):  
Yogesh Kumar ◽  
Harvijay Singh
Keyword(s):  
Virtual Screening ◽  
Active Site ◽  
Viral Infections ◽  
Drug Repurposing ◽  
Docking Study ◽  
Docking Studies ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Approved Drugs

<div>The rapidly enlarging COVID-19 pandemic caused by novel SARS-coronavirus 2 is a global</div><div>public health emergency of unprecedented level. Therefore the need of a drug or vaccine that</div><div>counter SARS-CoV-2 is an utmost requirement at this time. Upon infection the ssRNA genome</div><div>of SARS-CoV-2 is translated into large polyprotein which further processed into different</div><div>nonstructural proteins to form viral replication complex by virtue of virus specific proteases:</div><div>main protease (3-CL protease) and papain protease. This indispensable function of main protease</div><div>in virus replication makes this enzyme a promising target for the development of inhibitors and</div><div>potential treatment therapy for novel coronavirus infection. The recently concluded α-ketoamide</div><div>ligand bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al.</div><div>has revealed the potential inhibitor binding mechanism and the determinants responsible for</div><div>involved molecular interactions. Here, we have carried out a virtual screening and molecular</div><div>docking study of FDA approved drugs primarily targeted for other viral infections, to investigate</div><div>their binding affinity in Mpro active site. Virtual screening has identified a number of antiviral</div><div>drugs, top ten of which on the basis of their bending energy score are further examined through </div><div>molecular docking with Mpro. Docking studies revealed that drug Lopinavir-Ritonavir, Tipranavir</div><div>and Raltegravir among others binds in the active site of the protease with similar or higher</div><div>affinity than the crystal bound inhibitor α-ketoamide. However, the in-vitro efficacies of the drug</div><div>molecules tested in this study, further needs to be corroborated by carrying out biochemical and</div><div>structural investigation. Moreover, this study advances the potential use of existing drugs to be</div><div>investigated and used to contain the rapidly expanding SARS-CoV-2 infection.</div>

scholarly journals Unravelling promise of Indian herbal compounds as potential COVID-19 therapeutic agent

2020 ◽  
Author(s):  
SHAHENVAZ ALAM ◽  
SYEDA WARISUL FATIMA ◽  
SUNIL K. KHARE
Keyword(s):  
Drug Target ◽  
Glycyrrhizic Acid ◽  
Therapeutic Agent ◽  
Viral Infections ◽  
Docking Studies ◽  
Virus Life Cycle ◽  
E Protein ◽  
Medicinal Compounds ◽  
Protein Pockets ◽  
Novel Coronavirus

Abstract COVID-19 pandemic, an unprecedented devastation, humanity needs an urgent cure to save the mankind from this deadly disease. Over six million people have been infected worldwide, with 6.3% reported deaths till date. SARS-CoV-2 virus, responsible for Novel Coronavirus (COVID-19) disease has been isolated recently and the vaccine’s development is at nascent stage. At present, there are a few anecdotal evidences that anti-viral/anti-inflammatory/anti-malarial drugs can mitigate the disease. In the present study, we envision the potency of traditional Indian medicinal compounds that can be used as an effective drug. The viral SARS Coronavirus E protein plays a key role in virus life cycle and can be a potential drug target for the development of anti-SARS-CoV-2 drugs. Using the crystal structure of the CoV-E protein, we performed virtual PyRX screening of Indian medicinal compounds which are reported to have efficacy in the treatment of some viral infections. Molecular docking studies were evaluated based on scores analysed by CavityPlus. The herbal compounds used were found to be more efficient in inhibiting the virus as compared to commercially available drugs. The results showed that β-boswellic acid and Glycyrrhizic acid possessed the best binding as a ligand with target molecule having binding affinity of -9.1 kcal/mol amongst eleven compounds screened. The study demonstrated that these are found to be strong SARS-CoV-2E protein inhibitors as they revealed compatible, near perfect dock in the overlapping region of functional viral protein pockets. These potential hit compounds can pave a way for designing of anti-viral therapeutics.

scholarly journals Computational approach for the design of potential spike protein binding natural compounds in SARS- CoV2

2020 ◽  
Author(s):  
Anamika Basu ◽  
Anasua Sarkar ◽  
Ujjwal Maulik
Keyword(s):  
Natural Products ◽  
Protein Binding ◽  
Binding Site ◽  
Transmembrane Protein ◽  
Experimental Studies ◽  
Cost Effective ◽  
Docking Study ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
Novel Coronavirus

Abstract Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role as it is rapid, cost effective, compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus effected patients, in the present alarming situation. In this paper five phytochemicals which belong to flavonoid and anthraquinone subclass, selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. From the detail analysis of their molecular binding site on spike protein binding site with its receptor, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19.

scholarly journals Structural Diversity and Role of Phytochemicals against P38-α Mitogen-activated Protein Kinase and Epidermal Growth Factor Receptor Kinase Domain: A Privileged Computational Approach

2021 ◽  
Author(s):  
Amar Shankar ◽  
S.M. Gopinath ◽  
Shiva Prasad Kollur ◽  
P. Sushma ◽  
Anisha S. Jain ◽  
...  
Keyword(s):  
Hydrophobic Interactions ◽  
Growth Factor Receptor ◽  
Structural Diversity ◽  
Docking Study ◽  
Kinase Domain ◽  
Docking Studies ◽  
Mitogen Activated Protein Kinase ◽  
Standard Drug ◽  
Receptor Proteins ◽  
Egfr Kinase

Computational databases and tools in recent times have been proved to provide an essential aid for anticancer studies in the field of oncology. Molecular docking studies facilitate the structural diversity of plant-derived phytomolecules having anticancer properties against receptor proteins involved in cancer signaling pathways. The current study involves the investigation of phytocompounds-agasthisflavone, anacardic acid, zoapatanolide A, a purified product of the plant extract Amarogopinois546 were subjected to docking studies on p38-α MAPK and EGFR Kinase domain. The effectiveness of this study was evaluated by comparing the docking interactions of a standard drug, doxorubicin against the receptor molecules. The docking study is analyzed by compound estimated with lowest binding energy is considered to have the highest affinity towards the active site of the receptor proteins. The isolated plant compound Amarogopinois546 displayed the least binding score with a large number of hydrogen bonds and hydrophobic interactions towards the P38α MAP kinase receptor in comparison with the EGFR kinase domain. This preliminary result can strongly be supported for carrying out experimental evaluation in near future.

scholarly journals Marine Sulfated Polysaccharides as Promising Antiviral Agents: A Comprehensive Report and Modeling Study Focusing on SARS CoV-2

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 406
Author(s):  
Abdalla E. M. Salih ◽  
Bathini Thissera ◽  
Mohammed Yaseen ◽  
Ahmed S. I. Hassane ◽  
Hesham R. El-Seedi ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Protein S ◽  
Sulfated Polysaccharides ◽  
Protective Agent ◽  
Angiotensin Converting Enzyme 2 ◽  
Chondroitin Sulfate E ◽  
Novel Coronavirus ◽  
Potential Interactions

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is a novel coronavirus strain that emerged at the end of 2019, causing millions of deaths so far. Despite enormous efforts being made through various drug discovery campaigns, there is still a desperate need for treatments with high efficacy and selectivity. Recently, marine sulfated polysaccharides (MSPs) have earned significant attention and are widely examined against many viral infections. This article attempted to produce a comprehensive report about MSPs from different marine sources alongside their antiviral effects against various viral species covering the last 25 years of research articles. Additionally, these reported MSPs were subjected to molecular docking and dynamic simulation experiments to ascertain potential interactions with both the receptor-binding domain (RBD) of SARS CoV-2′s spike protein (S-protein) and human angiotensin-converting enzyme-2 (ACE2). The possible binding sites on both S-protein’s RBD and ACE2 were determined based on how they bind to heparin, which has been reported to exhibit significant antiviral activity against SARS CoV-2 through binding to RBD, preventing the virus from affecting ACE2. Moreover, our modeling results illustrate that heparin can also bind to and block ACE2, acting as a competitor and protective agent against SARS CoV-2 infection. Nine of the investigated MSPs candidates exhibited promising results, taking into consideration the newly emerged SARS CoV-2 variants, of which five were not previously reported to exert antiviral activity against SARS CoV-2, including sulfated galactofucan (1), sulfated polymannuroguluronate (SPMG) (2), sulfated mannan (3), sulfated heterorhamnan (8), and chondroitin sulfate E (CS-E) (9). These results shed light on the importance of sulfated polysaccharides as potential SARS-CoV-2 inhibitors.

scholarly journals Naturally Occurring Anthraquinones as Potential Inhibitors of SARS-CoV-2 Main Protease: A Molecular Docking Study

2020 ◽  
Author(s):  
Sourav Das ◽  
Atanu Singha Roy
Keyword(s):  
Molecular Docking ◽  
Drug Targets ◽  
Docking Study ◽  
Docking Studies ◽  
World Health ◽  
Molecular Docking Study ◽  
Inhibitory Potential ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Potential Inhibitors

<i>Background:</i> The novel coronavirus (COVID-19) has quickly spread throughout the globe, affecting millions of people. The World Health Organization (WHO) has recently declared this infectious disease as a pandemic. At present, several clinical trials are going on to identify possible drugs for treating this infection. SARS-CoV-2 M<sup>pro</sup> is one of the most critical drug targets for the blockage of viral replication. <i>Method:</i> The blind molecular docking analyses of natural anthraquinones with SARS-CoV-2 M<sup>pro</sup> were carried out in an online server, SWISSDOCK, which is based on EADock DSS docking software. <i>Results: </i>Blind molecular docking studies indicated that several<i> </i>natural antiviral anthraquinones could prove to be effective inhibitors for SARS-CoV-2 M<sup>pro</sup> of COVID-19 as they bind near the active site having the catalytic dyad, HIS41 and CYS145 through non-covalent forces. The anthraquinones showed less inhibitory potential as compared to the FDA approved drug, remdesivir.<i></i> <p><b><i>Conclusion:</i></b><i> </i>Among the natural anthraquinones<i>, </i>alterporriol Q could be the most potential inhibitor of SARS-CoV-2 M<sup>pro</sup> among the natural anthraquinones studied here, as its ∆<i>G</i> value differed from that of remdesivir only by 0.51 kcal/ mol. The uses of these alternate compounds might be favorable for the treatment of the COVID-19.</p>

scholarly journals In silico screening of JAK-STAT modulators from the antiviral plants of Indian traditional system of medicine with the potential to inhibit 2019 novel coronavirus

2020 ◽  
Author(s):  
Pukar Khanal ◽  
Taaza Duyu ◽  
BM Patil ◽  
Yadu Nandan Dey ◽  
Ismail Pasha ◽  
...  
Keyword(s):  
Immune System ◽  
Hepatitis Virus ◽  
Docking Study ◽  
Spike Protein ◽  
Murine Hepatitis Virus ◽  
Traditional System ◽  
Diarrhea Virus ◽  
Associated Proteins ◽  
Novel Coronavirus ◽  
Stat Pathway

Abstract Aim. The present study was aimed to identify the lead hits from reported anti-viral Indian medicinal plants to modulate the proteins through the JAK-STAT pathway and to identify the proteins that share the domain with coronavirus (COVID19) associated proteins i.e. 3CLpro, PLpro, and spike protein. Methods. The reported anti-viral plants were screened from the available databases and published literature; their phytoconstituents were retrieved, gene-expression was predicted and the modulated proteins in JAK-STAT pathway were predicted. The interaction between proteins was evaluated using STRING and the network between phytoconstituents and proteins was constructed using Cytoscape. The druglikeness score was predicted using MolSoft and the ADMET profile of phytoconstituents was evaluated using admetSAR2.0. The domain of three proteins i.e. 3CLpro, PLpro, and spike protein of coronavirus was compared using NCBI blastP against the RCSB database. Results. The majority of the phytoconstituents from the anti-viral plants were predicted to target TRAF5 protein in the JAK-STAT pathway; among them, vitexilactone was predicted to possess the highest druglikeness score. Proteins targeted in the JAK-STAT pathways were also predicted to modulate the immune system. Similarly, the docking study identified sesaminol 2-O-β-D-gentiobioside to possess the highest binding affinity with spike protein. Similarly, phylogeny comparison also identified the common protein domains with other stains of microbes like murine hepatitis virus strain A59, avian infectious bronchitis virus, and porcine epidemic diarrhea virus CV777. Conclusion. Although, the present study is based on computer simulations and database mining, it provides two important aspects in identifying the lead hits against coronavirus. First, targeting the JAK-STAT pathway in the corona-infected host by folk anti-viral agents can regulate the immune system which would inhibit spreading the virus inside the subject. Secondly, the well-known targets of coronavirus i.e. 3CLpro, PLpro, and spike protein share some common domains with other proteins of different microbial strains.

scholarly journals Structural analysis of COVID-19 spike protein in recognizing the ACE2 receptor of different mammalian species and its susceptibility to viral infection.

2020 ◽  
Author(s):  
Tirthankar Koley ◽  
Shivani Madaan ◽  
Sanghati Roy Chowdhury ◽  
Manoj Kumar ◽  
Punit Kaur ◽  
...  
Keyword(s):  
Hydrophobic Interactions ◽  
Interaction Analysis ◽  
Mammalian Species ◽  
Protein Docking ◽  
Glycosylation Site ◽  
Spike Protein ◽  
Amino Acid Residues ◽  
New Public Health ◽  
Potential Mode ◽  
Novel Coronavirus

Abstract The pandemic COVID-19 caused by a novel coronavirus SARS-CoV-2 spread worldwide as a new public health emergency. The SARS-CoV-2 infects humans by binding to glycosylated ACE2 receptor present in the inner lining of the lungs, heart, intestine and kidney. The COVID spike 2 protein recognizes the ACE2 receptor at the N-terminal helices of the metalloprotease domain. The residues Gln24, Thr27, Lys31, His34, Glu37, Asp38, Tyr41, Gln42 from helix α1; Leu79, Met82, Tyr83 from helix α2 and Gln325, Glu329, Asn330, Lys353 from loop connecting β4 and β5 strands form a concave surface surrounded by four glycosylation sites Asn53, Asn90, Asn103 and Asn322 form interactions with the spike protein. However, no significant data on the susceptibility of animals for infection or transmission. Therefore, we performed the comparative protein-protein docking analysis using the crystal structure of spike protein and homology models of the ACE2 receptor from 16 commonly found mammalian species to understand the potential mode of spike binding. Our comprehensive sequence and structure-based interaction analysis revealed the natural substitution of amino acid residues Gln24, His34, Phe40 and Met82 in the N-terminal α1 and α2 helices results in loss of crucial network of hydrogen-bonded and hydrophobic interactions with spike 2 RBD domain. Besides, the absence of N-linked glycosylation site Asn103 in other mammals further reduces the binding affinity between spike and ACE2 receptor. Hence, these changes explain the differences in the susceptibility and host pathogenesis in other mammalian species.

scholarly journals Anthraquinone Derivatives as an Immune Booster and their Therapeutic Option Against COVID-19

2020 ◽  
Vol 10 (5) ◽  
pp. 325-335 ◽  
Author(s):  
Pukar Khanal ◽  
B. M. Patil ◽  
Jagdish Chand ◽  
Yasmin Naaz
Keyword(s):  
Binding Energy ◽  
Binding Affinity ◽  
Immune Modulation ◽  
Therapeutic Option ◽  
Docking Study ◽  
Spike Protein ◽  
Pathway Database ◽  
Anthraquinone Derivatives ◽  
Novel Coronavirus ◽  
Immune Booster

Abstract Anthraquinone derivatives are identified for their immune-boosting, anti-inflammatory, and anti-viral efficacy. Hence, the present study aimed to investigate the reported anthraquinone derivatives as immune booster molecules in COVID-19 infection and evaluate their binding affinity with three reported targets of novel coronavirus i.e. 3C-like protease, papain-like protease, and spike protein. The reported anthraquinone derivatives were retrieved from an open-source database and filtered based on a positive druglikeness score. Compounds with positive druglikeness scores were predicted for their targets using DIGEP-Pred and the interaction among modulated proteins was evaluated using STRING. Further, the associated pathways were recorded concerning the Kyoto Encyclopedia of Genes and Genomes pathway database. Finally, the docking was performed using autodock4 to identify the binding efficacy of anthraquinone derivatives with 3C-like protease, papain-like protease, and spike protein. After docking the pose of ligand scoring minimum binding energy was chosen to visualize the ligand–protein interaction. Among 101 bioactives, 36 scored positive druglikeness score and regulated multiple pathways concerned with immune modulation and (non-) infectious diseases. Similarly, docking study revealed torososide B to possess the highest binding affinity with papain-like protease and 3C-like protease and 1,3,6-trihydroxy-2-methyl-9,10-anthraquinone-3-O-(6′-O-acetyl)-β-d-xylopyranosyl-(1 → 2)-β-d-glucopyranoside with spike protein. Graphic Abstract

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