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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

NSP5 (13)

ProteinS (13)

NSP3 (3)

ComplexRdRp (3)

ProteinN (2)


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SARS-CoV-2 Proteins
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    Vitamin C inhibits SARS coronavirus-2 main protease PROTEIN essential for viral replication

    Authors: Tek Narsingh Malla; Suraj Pandey; Ishwor Poudyal; Luis Aldama; Dennis Feliz; Moraima Noda; George N. Phillips Jr.; Emina A. Stojkovic; Marius Schmidt

    doi:10.1101/2021.05.02.442358 Date: 2021-05-03 Source: bioRxiv

    There is an urgent need for anti-viral agents that treat and/or prevent Covid-19 MESHD caused by SARS-Coronavirus (CoV-2) infections MESHD. The replication of the SARS CoV-2 is dependent on the activity of two cysteine proteases, a papain-like PROTEIN protease, PL-pro, and the 3C-like protease known as main protease PROTEIN Mpro PROTEIN or 3CLpro PROTEIN. The shortest and the safest path to clinical use is the repurposing of drugs with binding affinity to PLpro PROTEIN or 3CLpro PROTEIN that have an established safety profile in humans. Several studies have reported crystal structures of SARS-CoV-2 main protease PROTEIN in complex with FDA approved drugs such as those used in treatment of hepatitis C MESHD. Here, we report the crystal structure of 3CLpro PROTEIN in complex Vitamin C (L-ascorbate) bound to the protein's PROTEIN active site at 2.5 Angstrom resolution. We also demonstrate that L-ascorbate inhibits the 3CLpro PROTEIN in vitro at mmol/L concentrations. The crystal structure of the Vitamin C 3CLpro PROTEIN complex may aid future studies on the effect of Vitamin C not only on the coronavirus main protease PROTEIN but on related proteases of other infectious viruses. Since ascorbate is readily available, as an over-the-counter vitamin supplement, our results have the potential for development of a global and inexpensive antiviral treatment.

    Naturally occurring phytochemical as inhibitors from Catharanthus roseus: An In-silico approaches for drug development against COVID-19 MESHD

    Authors: Rishee K. Kalaria; Hiren K. Patel

    doi:10.21203/rs.3.rs-116443/v1 Date: 2020-11-26 Source: ResearchSquare

    The current outbreak of the novel 2019 Coronavirus disease MESHD ( COVID-19 MESHD) is caused by SARS-CoV-2, has developed a threat to the world's human population. There are no effective therapies or vaccines yet, urging the serious efforts to tackle this pandemic situation. SARS-CoV-2 spike PROTEIN protein, papain like protease PROTEIN protein (PLPRO), main protease PROTEIN ( 3CLpro PROTEIN) and RNA dependent DNA polymerase are key factors in the virus infectious process and have been identified as potential targets for therapeutic formulation. Most people in India depend on conventional Indian medicine (phytochemical compounds) to treat diseases MESHD due to lower cost, easier accessibility and no adverse effects. A lot of studies have recently shown that phytochemicals contain an effective anti-viral activity. This study aims to investigate phytochemicals metabolites from the IMPPAT database (Indian Medicinal Plants Database) in order to identify potential COVID-19 MESHD inhibitors using in silico approaches. Certain phytochemical compounds with structure analogs like hydroxychloroquine and chloroquine from the IMPPAT database were taken for interaction with SARS-CoV-2 proteins MESHD. The Apparicine, 12-Chlorotabersonine, AC1NSULH and Vindolininol identified from Catharanthus roseus were further checked the ADMET property as well as ‘Lipinski’s rule and resulted in a strong binding affinity of (-7.6,-7.5) and (-7.6 -7.5) kcal/mol respectively for spikes and papain like protease PROTEIN protein of SARS-CoV-2. Our results indicate that these specific compounds can be used as effective inhibitors and help to pace up the drug development against SARS-CoV-2. Further investigation and testing of these inhibitors against SARS‐CoV‐2 are however required to check their clinical trial candidacy.

    Multi-Targeting Approach in Selection of Potential Molecule for COVID-19 MESHD Treatment

    Authors: Varalakshmi Velagacherla; Akhil Suresh; Chetan H Mehta; Yogendra Nayak; Usha Y Nayak

    doi:10.21203/rs.3.rs-101359/v1 Date: 2020-11-01 Source: ResearchSquare

    Background: Coronavirus disease ( COVID-19 MESHD) caused by the severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) is now a pandemic which began in Wuhan province of China. Drug discovery teams around the globe are in a race to develop a medicine for its management. For a novel molecule to enter into the market it takes time and the ideal way is to exploit the already approved drugs and repurpose them to use therapeutically.Methods: In this work, we have attempted to screen selected molecules that have shown an affinity towards multiple protein targets of COVID-19 MESHD using Schrödinger suit. Molecules were selected from approved antiviral, anti-inflammatory or immunomodulatory classes. The viral proteins selected were angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC), main protease PROTEIN ( Mpro PROTEIN) and spike protein PROTEIN. Computational tools such as molecular docking, prime MM-GBSA, induced-fit docking (IFD) and molecular dynamics ( MD MESHD) simulations were used to identify the most suitable molecule that forms a stable interaction with the selected viral proteins.Results: The ligand-binding stability for the viral proteins PDB-IDs 1ZV8 ( spike protein PROTEIN), 5R82 ( Mpro PROTEIN) and 6M1D ( ACE2 HGNC), was in the order of Nintedanib>Quercetin, Nintedanib>Darunavir, Nintedanib> Baricitinib respectively. The MM-GBSA, IFD, and MD simulation studies infer that the drug nintedanib has the highest binding stability among the shortlisted molecules towards the selected viral target proteins. Conclusion: Nintedanib, which is primarily used for idiopathic pulmonary fibrosis MESHD, can be considered for repurposing and used in the management of COVID-19 MESHD

    Computational Modeling Indicates A Decreased Affinity of SARS-CoV-2 to ACE2 HGNC by Steroids

    Authors: Alireza Mansouri; Rasoul Kowsar; Khaled Sadeghi; Akio Miyamoto

    doi:10.21203/rs.3.rs-86139/v1 Date: 2020-09-30 Source: ResearchSquare

    The novel coronavirus disease MESHD ( COVID-19 MESHD) presently poses significant concerns around the world. Latest reports show that the degree of disease and mortality of COVID-19 MESHD infected MESHD patients may vary from gender to gender with a very high risk of death MESHD for seniors. It was hypothesized that sex steroid hormones estradiol (E2), progesterone (P4), testosterone (T), and dexamethasone (DEX) may change the interaction of coronavirus spike protein PROTEIN (CSP) with angiotensin converting enzyme-2 ( ACE2 HGNC). Data showed that E2 was more strongly to interact with the main protease PROTEIN of the coronavirus, while T had the lowest affinity for CSP. The binding energy of the CSP to ACE2 HGNC was increased in the presence of steroids; the greatest increase was observed by DEX and E2. The binding free energy of the CSP to ACE2 HGNC was the highest in the presence of E2 and DEX. Together, the interaction between CSP and ACE2 HGNC can be disrupted by E2 and to a greater extent by DEX, in part explaining the lower incidence of COVID-19 MESHD infection in women than men. The potential use of E2 and DEX to reduce coronavirus attachment MESHD to ACE2 HGNC in the early phase of the coronavirus invasion needs to be clinically investigated.

    Structural insights into decreased affinity of SARS-CoV-2 to ACE2 HGNC by steroids

    Authors: Alireza Mansouri; Rasoul Kowsar; Khaled Sadeghi; Akio Miyamoto

    doi:10.21203/rs.3.rs-83198/v1 Date: 2020-09-24 Source: ResearchSquare

    The novel coronavirus disease MESHD ( COVID-19 MESHD) presently poses significant concerns around the world. Latest reports show that the degree of disease and mortality of COVID-19 MESHD infected MESHD patients may vary from gender to gender with a very high risk of death MESHD for seniors. Clearly, different levels of sex steroid hormones are found in both men and women. It was hypothesized that sex steroid hormones estradiol (E2), progesterone (P4), and testosterone (T) may change the interaction of coronavirus spike protein PROTEIN with angiotensin converting enzyme-2 ( ACE2 HGNC, which is the major SARS-CoV-2 cell entry receptor.) in the presence or absence of dexamethasone (DEX, the potential anti-inflammatory agents). Data showed that E2 was more strongly to interact with the main protease PROTEIN of the coronavirus, while T had the lowest affinity for coronavirus spike protein PROTEIN than E2 and P4. The binding energy of the spike protein PROTEIN to ACE2 HGNC was increased in the presence of five molecules of each steroid; the greatest increase was observed by DEX and E2. The binding free energy of the spike protein PROTEIN to ACE2 HGNC was the highest in the presence of both E2 and DEX HGNC molecules. Together, the interaction between spike protein PROTEIN and ACE2 HGNC can be disrupted by female sex steroid hormone E2 and to a greater extent by E2 and anti-inflammatory DEX, in part explaining the lower incidence of COVID-19 MESHD infection in women than men. The potential use of E2 and DEX HGNC to reduce coronavirus attachment MESHD to ACE2 HGNC in the early phase of the coronavirus invasion needs to be clinically investigated.

    Allergen Fragrance Molecules: A Potential Relief for COVID-19 MESHD

    Authors: Aslı Deniz Aydın; Faruk Altınel; Hüseyin Erdoğmuş; Cagdas Devrim Son

    doi:10.21203/rs.3.rs-57251/v1 Date: 2020-08-11 Source: ResearchSquare

    Background: The latest coronavirus SARS-CoV-2 MESHD, discovered in China and rapidly spread Worldwide. COVID-19 MESHD affected millions of people and killed hundreds of thousands worldwide. There are many ongoing studies investigating drug(s) suitable for preventing and/or treating this pandemic; however, there are no specific drugs or vaccines available to treat or prevent SARS-CoV-2 as of today.Methods: 58 fragrance materials, which are classified as allergen fragrance molecules, were selected and used in this study. Docking simulations were carried out using four functional proteins; the Covid19 MESHD Main Protase ( Mpro PROTEIN), Receptor binding domain (RBD) of spike protein PROTEIN, Nucleocapsid, and host Bromodomain protein ( BRD2 HGNC), as target macromolecules. Three different software, AutoDock, AutoDock Vina (Vina), and Molegro Virtual Docker ( MVD HGNC), running a total of four different docking protocol with optimized energy functions were used. Results were compared with the five molecules reported in the literature as potential drugs against COVID-19 MESHD. Virtual screening was carried out using Vina, molecules satisfying our cut-off (-6.5 kcal/mol) binding affinity was confirmed by MVD HGNC. Selected molecules were analyzed using the flexible docking protocol of Vina and AutoDock default settings MESHD.  Results: Ten out of 58 allergen fragrance molecules were selected for further docking studies. Mpro PROTEIN and BRD2 HGNC are potential targets for the tested allergen fragrance molecules, while RBD and Nucleocapsid showed weak binding energies. According to AutoDock results, three molecules, Benzyl Cinnamate, Dihydroambrettolide, and Galaxolide, had good binding affinities to BRD2 HGNC. While Dihydroambrettolide and Galaxolide showed the potential to bind to Mpro PROTEIN, Sclareol and Vertofix had the best calculated binding affinities to this target. When the flexible docking results analyzed, all the molecules tested had better calculated binding affinities as expected. Benzyl Benzoate and Benzyl Salicylate showed good binding affinities to BRD2 HGNC. In the case of Mpro PROTEIN, Sclareol had the lowest binding affinity among all the tested allergen fragrance molecules.   Conclusion: Allergen fragrance molecules are readily available, cost-efficient, and shown to be safe for human use. Results showed that several of these molecules had comparable binding affinities as the potential drug molecules reported in the literature to target proteins. Thus, these allergen molecules at correct doses could have significant health benefits. 

    Discovery of Natural Phenol Catechin as a Multitargeted Agent Against SARS-CoV-2 For the Plausible Therapy of COVID-19 MESHD

    Authors: Chandra Bhushan Mishra; Preeti Pandey; Ravi Datta Sharma; Raj Kumar Mongre; Andrew M Lynn; Rajendra Prasad; Raok Jeon; Amresh Prakash

    doi:10.26434/chemrxiv.12752402.v1 Date: 2020-08-04 Source: ChemRxiv

    The global pandemic crisis, COVID-19 MESHD caused by severe acute respiratory syndrome coronavirus MESHD 2 (SARS-CoV-2) has claimed the lives of millions of people across the world. Development and testing of anti-SARS-CoV-2 drugs or vaccines, are not turned to be realistic in the timeframe needed to combat this pandemic. Thus, rigorous efforts are still ongoing for the drug repurposing as a clinical treatment strategy to control COVID-19 MESHD. Here we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, which are crucially involved in the viral-host interaction, replication of the virus inside the host, disease progression and transmission of coronavirus infection. Virtual screening of 72 FDA approved potential antiviral drugs against the target proteins: Spike (S PROTEIN) glycoprotein, human angiotensin-converting enzyme 2 ( hACE2 HGNC), 3-chymotrypsin- like cysteine protease PROTEIN ( 3CLpro PROTEIN), Cathepsin L HGNC, Nucleocapsid protein PROTEIN, RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN) and nonstructural protein 6 ( NSP6 PROTEIN) resulted in the selection of seven drugs which preferentially binds to the target proteins. Further, the molecular interactions determined by MD simulation, free energy landscape and the binding free energy estimation, using MM-PBSA revealed that among 72 drug molecules, catechin (flavan-3-ol) can effectively bind to 3CLpro PROTEIN, Cathepsin L HGNC, RBD of S protein PROTEIN, NSP-6, and Nucleocapsid protein PROTEIN. It is more conveniently involved in key molecular interactions, showing binding free energy (ΔGbind) in the range of -5.09 kcal/mol ( Cathepsin L HGNC) to -26.09 kcal/mol ( NSP6 PROTEIN). At the binding pocket, catechin is majorly stabilized by the hydrophobic interactions, displays ΔEvdW values -7.59 to -37.39 kcal/mol. Thus, the structural insights of better binding affinity and favourable molecular interaction of catechin towards multiple target proteins, signifies that catechin can be potentially explored as a multitargeted agent in the rational design of effective therapies against COVID-19 MESHD.

    Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease PROTEIN ( Mpro PROTEIN) and Spike ( S) Glycoprotein PROTEIN Inhibitors: A Molecular Docking Study

    Authors: Trina Ekawati Tallei; Sefren Geiner Tumilaar; Nurdjannah Jane Niode; Fatimawali Fatimawali; Billy Johnson Kepel; Rinaldi Idroes; Yunus Effendi

    id:10.20944/preprints202004.0102.v3 Date: 2020-07-01 Source: Preprints.org

    Since the outbreak of the COVID-19 MESHD ( Coronavirus Disease MESHD 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease PROTEIN ( Mpro PROTEIN) and Spike ( S) glycoprotein PROTEIN of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein PROTEIN inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro PROTEIN inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19 MESHD. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19 MESHD. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

    Temporal evolution and adaptation of SARS-COV 2 codon usage

    Authors: Maddalena Dilucca; Sergio Forcelloni; Andrea Giansanti; Alexandros Georgakilas; Athanasia Pavlopoulou

    doi:10.1101/2020.05.29.123976 Date: 2020-06-03 Source: bioRxiv

    The outbreak of severe acute respiratory syndrome-coronavirus-2 MESHD (SARS-CoV-2) has caused an unprecedented pandemic. Since the first sequenced whole-genome of SARS-CoV-2 on January 2020, the identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. In this study, we compared 15,259 SARS-CoV-2 genomes isolated from 60 countries since the outbreak of this novel coronavirus with the first sequenced genome in Wuhan to quantify the evolutionary divergence of SARS-CoV-2. Thus, we compared the codon usage patterns, every two weeks, of 13 of SARS-CoV-2 genes encoding for the membrane protein (M PROTEIN), envelope (E), spike surface glycoprotein (S PROTEIN), nucleoprotein (N PROTEIN), non-structural 3C-like proteinase ( 3CLpro PROTEIN), ssRNA-binding protein ( RBP HGNC), 2-O-ribose methyltransferase (OMT), endoRNase (RNase), helicase HGNC, RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN), Nsp7, Nsp8, and exonuclease ExoN. As a general rule, we find that SARS-CoV-2 genome tends to diverge over time by accumulating mutations on its genome and, specifically, on the coding sequences for proteins N PROTEIN and S. Interestingly, different patterns of codon usage were observed among these genes. Genes S, Nsp7, NSp8, tend to use a norrower set of synonymous codons that are better optimized to the human host. Conversely, genes E PROTEIN and M consistently use a broader set of synonymous codons, which does not vary with respect to the reference genome. We identified key SARS-CoV-2 genes (S, N, ExoN, RNase, RdRp PROTEIN, Nsp7 and Nsp8) suggested to be causally implicated in the virus adaptation to the human host.

    Natural lead molecules probably act as potential inhibitors against prospective targets of SARS-CoV-2: Therapeutic insight for COVID-19 MESHD from computational modelling, molecular docking and dynamic simulation studies

    Authors: Sinosh Skariyachan; Dharshini Gopal; Aditi G Muddebihalkar; 3Akshay Uttarkar; 3Vidya Niranjan

    doi:10.21203/rs.3.rs-33180/v1 Date: 2020-06-02 Source: ResearchSquare

    SARS-CoV-2 causing COVID-19 MESHD responsible for more than 3.46 lakhs deaths MESHD and 5.4 lakhs confirmed cases around 210 countries as of 25 May 2020. This study focuses on the binding potential of natural lead molecules towards prospective molecular targets of SARS-CoV-2 by computational virtual screening and molecular dynamic (MD) simulation. As there are no approved vaccines/drugs, it is very essential to undertake COVID-19 MESHD research and identify therapeutic intervention. By thorough literature survey and database search, 14 probable targets based on their virulent functions in coronavirus infection MESHD were identified, 11 of them possessed native structures and 03 of them lack native structures were computationally modeled and validated. 92 natural molecules were screened; their drug likeliness MESHD and pharmacokinetic features were predicted. Four lead molecules with ideal drug-likeliness MESHD and pharmacokinetic features were selected and docked against 14 targets and their binding affinities were compared to the binding of Chloroquine and Hydroxychloroquine to their usual targets. The stabilities of selected docked complexes were confirmed by MD simulation and energy calculations. Four natural molecules demonstrated profound binding to most of the prioritized targets, especially, Hyoscyamine and Tamaridone to spike glycoprotein PROTEIN and Rotiorinol-C and Scutifoliamide-A to replicase polyprotein-1ab ( main protease PROTEIN) of SARS-CoV-2 showed better binding, conformational and dynamic stability than the binding of Chloroquine and its usual target glutathione-S-transferase. The aforementioned lead molecules probably used to develop novel therapeutic agents towards the molecular targets of SARS-CoV-2 and the prediction probably provide significant insight for structure-based drug development against COVID-19 MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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