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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (4)

ComplexRdRp (4)

ProteinS (3)

NSP5 (2)

NSP12 (1)


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    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.

    A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 MESHD Patients

    Authors: Dharmendra Kumar Maurya

    doi:10.26434/chemrxiv.12630539.v1 Date: 2020-07-09 Source: ChemRxiv

    The current outbreak of the corona virus disease 2019 ( COVID-19 MESHD), has affected almost entire world and become pandemic now. Currently, there is neither any FDA approved drugs nor any vaccines available to control it. Very recently in Bangladesh, a group of doctors reported astounding success in treating patients suffering from COVID-19 MESHD with two commonly used drugs, Ivermectin and Doxycycline. In the current study we have explored the possible mechanism by which these drugs might have worked for the positive response in the COVID-19 MESHD patients. To explore the mechanism we have used molecular docking and molecular dynamics simulation approach. Effectiveness of Ivermectin and doxycycline were evaluated against Main Protease PROTEIN ( Mpro PROTEIN), Spike (S) protein PROTEIN, Nucleocapsid (N PROTEIN), RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN, NSP12 PROTEIN), ADP Ribose Phosphatase ( NSP3 HGNC NSP3 PROTEIN), Endoribonuclease ( NSP15 PROTEIN) and methyltransferase ( NSP10 PROTEIN- NSP16 PROTEIN complex) of SARS-CoV-2 as well as human angiotensin converting enzyme 2 HGNC ( ACE2 HGNC) receptor. Our study shows that both Ivermectin and doxycycline have significantly bind with SARS-CoV-2 proteins but Ivermectin was better binding than doxycycline. Ivermectin showed a perfect binding site to the Spike-RBD and ACE2 HGNC interacting region indicating that it might be interfering in the interaction of spike with ACE2 HGNC and preventing the viral entry in to the host cells. Ivermectin also exhibited significant binding affinity with different SARS-CoV-2 structural and non-structural proteins (NSPs) which have diverse functions in virus life cycle. Significant binding of Ivermectin with RdRp PROTEIN indicate its role in the inhibition of the viral replication and ultimately impeding the multiplication of the virus. Ivermectin also possess significant binding affinity with NSP3 HGNC NSP3 PROTEIN, NSP10 PROTEIN, NSP15 PROTEIN and NSP16 PROTEIN which helps virus in escaping from host immune system. Molecular dynamics simulation study shows that binding of the Ivermectin with Mpro PROTEIN, Spike, NSP3 HGNC NSP3 PROTEIN, NSP16 PROTEIN and ACE2 HGNC was quiet stable. Thus, our docking and simulation studies reveal that combination of Ivermectin and doxycycline might be executing the effect by inhibition of viral entry and enhance viral load clearance by targeting various viral functional proteins.

    Genomic diversity and hotspot mutations in 30,983 SARS-CoV-2 genomes: moving toward a universal vaccine for the "confined virus"?

    Authors: Tarek Alouane; Meriem Laamarti; Abdelomunim Essabbar; Mohammed Hakmi; El Mehdi Bouricha; M.W. Chemao-Elfihri; Souad Kartti; Nasma Boumajdi; Houda Bendani; Rokia Laamarti; Fatima Ghrifi; Loubna Allam; Tarik Aanniz; Mouna Ouadghiri; Naima El Hafidi; Rachid El Jaoudi; Houda Benrahma; Jalil El Attar; Rachid Mentag; Laila Sbabou; Chakib Nejjari; Saaid Amzazi; Lahcen Belyamani; Azeddine Ibrahimi

    doi:10.1101/2020.06.20.163188 Date: 2020-06-21 Source: bioRxiv

    The COVID-19 MESHD COVID-19 MESHD pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains. From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from December 24, 2019, to May 13, 2020, according to the GISAID database. Our analysis revealed the presence of 3,206 variant sites, with a uniform distribution of mutation types in different geographic areas. Remarkably, a low frequency of recurrent mutations has been observed; only 169 mutations (5.27%) had a prevalence greater than 1% of genomes. Nevertheless, fourteen non-synonymous hotspot mutations (> 10%) have been identified at different locations along the viral genome; eight in ORF1ab PROTEIN polyprotein (in nsp2 HGNC, nsp3 HGNC, transmembrane domain, RdRp PROTEIN, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein PROTEIN and one in each of three proteins: spike PROTEIN, ORF3a PROTEIN, and ORF8 PROTEIN. Moreover, 36 non-synonymous mutations were identified in the RBD of the spike protein PROTEIN with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike PROTEIN protein to the human ACE2 HGNC receptor. These results along with mutational frequency dissimilarity and intra-genomic divergence of SARS-CoV-2 could indicate that the SARS-CoV-2 is not yet adapted to its host. Unlike the influenza virus or HIV viruses, the low mutation rate of SARS-CoV-2 makes the development of an effective global vaccine very likely.

    Prediction of SARS-CoV interaction with host proteins during lung aging reveals a potential role for TRIB3 HGNC in COVID-19 MESHD.

    Authors: Diogo de Moraes; Brunno Vivone Buquete Paiva; Sarah Santiloni Cury; Joao Pessoa Araujo Jr.; Marcelo Alves da Silva Mori; Robson Francisco Carvalho

    doi:10.1101/2020.04.07.030767 Date: 2020-04-09 Source: bioRxiv

    COVID-19 MESHD is prevalent in the elderly. Old individuals are more likely to develop pneumonia MESHD and respiratory failure MESHD due to alveolar damage MESHD, suggesting that lung senescence may increase the susceptibility to SARS-CoV-2 infection MESHD and replication. Considering that human coronavirus (HCoVs; SARS-CoV-2 and SARS-CoV) require host cellular factors for infection and replication, we analyzed Genotype-Tissue Expression (GTEx) data to test whether lung aging is associated with transcriptional changes in human protein-coding genes that potentially interact with these viruses. We found decreased expression of the gene tribbles homolog 3 ( TRIB3 HGNC) during aging in male individuals, and its protein was predicted to interact with HCoVs nucleocapsid protein PROTEIN and RNA-dependent RNA polymerase PROTEIN. Using publicly available lung single-cell data, we found TRIB3 HGNC expressed mainly in alveolar MESHD epithelial cells that express SARS-CoV-2 receptor ACE2 HGNC. Functional enrichment analysis of age-related genes, in common with SARS-CoV-induced perturbations, revealed genes associated with the mitotic cell cycle and surfactant metabolism. Given that TRIB3 HGNC was previously reported to decrease virus infection MESHD and replication, the decreased expression of TRIB3 HGNC in aged lungs may help explain why older male patients are related to more severe cases of the COVID-19 MESHD. Thus, drugs that stimulate TRIB3 HGNC expression should be evaluated as a potential therapy for the disease.

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MeSH Disease
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SARS-CoV-2 Proteins


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