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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

NSP5 (7)

ProteinS (4)

ComplexRdRp (2)

ProteinN (1)

NSP6 (1)


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SARS-CoV-2 Proteins
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    Mild and severe SARS-CoV-2 infection MESHD induces respiratory and intestinal microbiome changes in the K18- hACE2 HGNC transgenic mouse model

    Authors: Brittany A Seibert; Joaquin Caceres; Stivalis Cardenas-Garcia; Silvia Carnaccini; Ginger Geiger; Daniela Rajão; Elizabeth A Ottesen; Daniel R. Perez

    doi:10.1101/2021.04.20.440722 Date: 2021-04-23 Source: bioRxiv

    Transmission of the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), has resulted in millions of deaths MESHD and declining economies around the world. K18- hACE2 HGNC mice develop disease resembling severe SARS-CoV-2 infection MESHD in a virus dose-dependent manner. The relationship between SARS-CoV-2 and the intestinal or respiratory microbiome is not fully understood. In this context, we characterized the cecal and lung microbiome of SARS-CoV-2 challenged K18- hACE2 HGNC transgenic mice in the presence or absence of treatment with the Mpro PROTEIN inhibitor GC376. Cecum microbiome showed decreased Shannon and Inv Simpson diversity index correlating with SARS-CoV-2 infection MESHD dosage and a difference of Bray-Curtis MESHD dissimilarity distances among control and infected mice. Bacterial phyla such as Firmicutes, particularly Lachnospiraceae and Oscillospiraceae, were significantly less abundant while Verrucomicrobiota, particularly the family Akkermansiaceae, were increasingly more prevalent during peak infection in mice challenged with a high virus dose. In contrast to the cecal microbiome, the lung microbiome showed similar microbial diversity among the control, low and high challenge virus groups, independent of antiviral treatment. Bacterial phyla in the lungs such as Bacteroidota decreased while Firmicutes and Proteobacteria were significantly enriched in mice challenged with a high dose of SARS-CoV-2. In summary, we identified changes in the cecal and lung microbiome of K18- hACE2 HGNC mice with severe clinical signs of SARS-CoV-2 infection MESHD.

    Efficacy of GC-376 against SARS-CoV-2 virus infection MESHD in the K18 hACE2 HGNC transgenic mouse model

    Authors: C. Joaquin Caceres; Stivalis Cardenas-Garcia; Silvia Carnaccini; Brittany Seibert; Daniela S Rajao; Jun Wang; Daniel R Perez; Amanda J. Martinot; Cesar Piedra-Mora; Sidney Beecy; Sarah Ducat; Ronnie Chamanza; Sietske Rosendahl Huber; Leslie van der Fits; Erica N. Borducchi; Michelle Lifton; Jinyan Liu; Felix Nampanya; Shivani Patel; Lauren Peter; Lisa H. Tostanoski; Laurent Pessaint; Alex Van Ry; Brad Finneyfrock; Jason Velasco; Elyse Teow; Renita Brown; Anthony Cook; Hanne Andersen; Mark G. Lewis; Hanneke Schuitemaker; Dan H. Barouch; Christian Lavallee; Pierre-Olivier Hetu; Jean-Sebastien Paquette; Sylvie Levesque; Marieve Cossette; Anna Nozza; Malorie Chabot-Blanchet; Marie-Pierre Dube; Marie-Claude Guertin; Guy Boivin

    doi:10.1101/2021.01.27.428428 Date: 2021-01-27 Source: bioRxiv

    The COVID-19 pandemic MESHD caused by the Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a Mpro PROTEIN inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18- hACE2 HGNC mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18- hACE2 HGNC mice and produced milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation MESHD in comparison to vehicle-treated controls, most notably in the brain in mice challenged with a low virus dose. Although GC-376 was not sufficient to improve neither clinical symptoms nor survival, it did show a positive effect against SARS-CoV-2 in vivo. This study supports the notion that the K18- hACE2 HGNC mouse model is suitable to study antiviral therapies against SARS-CoV-2, and GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection MESHD.

    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.

    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.

    Discovery of Multi-Target-Directed Ligands by Targeting Host-specific SARS-CoV-2’s Structurally Conserved Main Protease PROTEIN

    Authors: Rakesh Joshi; Shounak Jagdale; Sneha Bansode; S. Shiva Shankar; Meenakshi Tellis; Vaibhav Kumar Pandya; Ashok Giri; Mahesh Kulkarni

    id:10.20944/preprints202004.0068.v2 Date: 2020-04-09 Source: Preprints.org

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD has resulted in the current COVID-19 MESHD COVID-19 MESHD pandemic. Worldwide this disease has infected around 1.5 million individuals with a mortality rate ranging from 5 to 10%. It has also imposed extreme challenges on global health, economy, and social behavior. Due to the unavailability of therapeutics, several efforts are going on in the drug discovery to control the SARS-CoV-2 viral infection MESHD. The main protease PROTEIN (MPro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of MPro, we have performed phylogenetic and SSN analysis, that depicted divergence of Coronaviridae MPro in five clusters specific to viral hosts. This clustering was also corroborated with the comparison of MPro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. This conservation can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 MPro. In agreement with this, we performed screening of the custom-made library of ~7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 MPro as the primary target. We identified several natural molecules that strongly binds to SARS-CoV-2 MPro among which top seven molecules are d-Viniferin, Myricitrin, Taiwanhomoflavone A, Lactucopicrin 15-oxalate, Nympholide A, Biorobin and Phyllaemblicin B. Most of the predicted lead molecules are from Vitis vinifera, also reported for anti-tussive and/or antiviral activities. These molecules also showed strong binding with other main targets RdRp PROTEIN and hACE-2 HGNC. We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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