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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

NSP10 (8)

NSP3 (4)

NSP16 (4)

NSP5 (4)

ComplexRdRp (4)


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SARS-CoV-2 Proteins
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    SARS-CoV-2 antibody signatures for predicting the outcome of COVID-19 MESHD

    Authors: Qing Lei; Caizheng Yu; Yang Li; Hongyan Hou; Zhaowei Xu; Meian He; Ziyong Sun; Feng Wang; Sheng-ce Tao; Xionglin Fan

    doi:10.1101/2020.11.10.20228890 Date: 2020-11-13 Source: medRxiv

    The COIVD-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for predicting the outcome of COVID-19 MESHD. Growing evidences have revealed that SARS-CoV-2 specific antibodies remain elevated with disease progression and severity in COIVD-19 patients. We assumed that antibodies may serve as biomarkers for predicting disease outcome. By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgM/ IgG responses against 20 SARS-CoV-2 proteins in 1,034 hospitalized COVID-19 MESHD patients on admission, who were followed till 66 days. The microarray results were correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 MESHD mortality. We found that high level of IgM against ORF7b PROTEIN at the time of hospitalization is an independent predictor of patient survival (p trend = 0.002), while levels of IgG responses to 6 non-structural proteins PROTEIN and 1 accessory protein, i. e PROTEIN., NSP4 HGNC NSP4 PROTEIN, NSP7 PROTEIN, NSP9 PROTEIN, NSP10 PROTEIN, RdRp PROTEIN ( NSP12 PROTEIN), NSP14 PROTEIN, and ORF3b PROTEIN, possess significant predictive power for patient death MESHD, even after further adjustments for demographics, comorbidities, and common laboratory markers for disease severity (all with p trend < 0.05). Spline regression analysis indicated that the correlation between ORF7b PROTEIN IgM, NSP9 PROTEIN IgG, and NSP10 PROTEIN IgG and risk of COVID-19 MESHD mortality is linear (p = 0.0013, 0.0073 and 0.0003, respectively). Their AUCs for predictions, determined by computational cross-validations (validation1), were 0.74 (cut-off = 7.59), 0.66 (cut-off = 9.13), and 0.68 (cut-off = 6.29), respectively. Further validations were conducted in the second and third serial samples of these cases (validation2A, n = 633, validation2B, n = 382), with high accuracy of prediction for outcome. These findings have important implications for improving clinical management, and especially for developing medical interventions and vaccines.

    In silico analyses on the comparative sensing of SARS-CoV-2 mRNA by intracellular TLRs of human

    Authors: Abhigyan Choudhury; Nabarun Chandra Das; Ritwik Patra; Manojit Bhattacharya; Suprabhat Mukherjee; Kianna M. Nguyen; Ming H. Ho; Jung-Eun Shin; Jared Feldman; Blake M. Hauser; Timothy M. Caradonna; Laura M. Wingler; Aaron G. Schmidt; Debora S. Marks; Jonathan Abraham; Andrew C. Kruse; Chang C. Liu

    doi:10.1101/2020.11.11.377713 Date: 2020-11-11 Source: bioRxiv

    The worldwide outbreak of COVID-19 MESHD COVID-19 MESHD pandemic caused by SARS-CoV-2 leads to loss of mankind and global economic stability. The continuous spreading of the disease and its pathogenesis takes millions of lives of peoples and the unavailability of appropriate therapeutic strategy makes it much more severe. Toll-like receptors (TLRs) are the crucial mediators and regulators of host immunity. The role of several TLRs in immunomodulation of host by SARS-CoV-2 is recently demonstrated. However, the functionality of human intracellular TLRs including TLR3 HGNC,7,8 and 9 is still being untested for sensing of viral RNA. This study is hoped to rationalize the comparative binding and sensing of SARS-CoV-2 mRNA towards the intracellular TLRs, considering the solvent-based force-fields operational in the cytosolic aqueous microenvironment that predominantly drive these reactions. Our in-silico study on the binding of all mRNAs with the intracellular TLRs shown that the mRNA of NSP10 PROTEIN, S2, and E proteins PROTEIN of SARS-CoV-2 are potent enough to bind with TLR3 HGNC, TLR9 HGNC, and TLR7 HGNC and trigger downstream cascade reactions, and may be used as an option for validation of therapeutic option and immunomodulation against COVID-19 MESHD.

    Global variation in the SARS-CoV-2 proteome reveals the mutational hotspots in the drug and vaccine candidates

    Authors: L Ponoop Prasad Patro; Chakkarai Sathyaseelan; Patil Pranita Uttamrao; Thenmalarchelvi Rathinavelan

    doi:10.1101/2020.07.31.230987 Date: 2020-07-31 Source: bioRxiv

    To accelerate the drug and vaccine development against the severe acute respiratory syndrome MESHD virus 2 (SARS-CoV-2), a comparative analysis of SARS-CoV-2 proteome has been performed in two phases by considering manually curated 31389 whole genome sequences from 84 countries. Among the 9 mutations that occur at a high significance (T85I-NPS2, L37F- NSP6 PROTEIN, P323L- NSP12 PROTEIN, D614G-spike, Q57H- ORF3a PROTEIN, G251V- ORF3a PROTEIN, L84S- ORF8 PROTEIN, R203K-nucleocapsid and G204R-nucleocapsid), R203K-nucleocapsid and G204R-nucleocapsid are co-occurring (dependent) mutations and P323L- NSP12 PROTEIN and D614G-spike often appear simultaneously. Other notable variations that appear with a moderate to low significance are, M85- NSP1 HGNC deletion, D268- NSP2 HGNC NSP2 PROTEIN deletion, 112 amino acids deletion in ORF8 PROTEIN, a phenylalanine insertion amidst F34-F36 ( NSP6 PROTEIN) and several co-existing (dependent) substitution/deletion (I559V & P585S in NSP2 HGNC NSP2 PROTEIN, P504L & Y541C in NSP13 PROTEIN, G82 & H83 deletions in NSP1 HGNC and K141, S142 & F143 deletions in NSP2 HGNC NSP2 PROTEIN) mutations. P323L- NSP12 PROTEIN, D614G-spike, L37F- NSP6 PROTEIN, L84S- ORF8 PROTEIN and the sequences deficient of the high significant mutations have led to 4 major SARS-CoV-2 clades. The top 5 countries bearing all the high significant and majority of the moderate significant mutations are: USA, England, Wales, Australia and Scotland. Further, the majority of the significant mutations have evolved in the first phase and have already transmitted around the globe indicating the positive selection pressure. Among the 26 SARS-CoV-2 proteins, nucleocapsid PROTEIN protein, ORF3a PROTEIN, ORF8 PROTEIN, RNA dependent RNA polymerase PROTEIN and spike exhibit a higher heterogeneity compared with the rest of the proteins. However, NSP9 PROTEIN, NSP10 PROTEIN, NSP8 PROTEIN, the envelope protein PROTEIN and NSP4 HGNC NSP4 PROTEIN are highly resistant to mutations and can be exploited for drug/vaccine development.

    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.

    In-Silico Molecular Docking Show Mitocurcumin can Potentially Block Innate Immune Evasion Mechanism of SARS-CoV-2 and Enhance Viral Load Clearance

    Authors: Debojyoti Pal; Rahul Checker; Vijay Kutala; Santosh Sandur

    doi:10.26434/chemrxiv.12439967.v1 Date: 2020-06-09 Source: ChemRxiv

    In the present work, we have employed a molecular docking approach to study the ability of mitocurcumin (MC), a triphenyl phosphonium conjugated curcumin derivative, to inhibit SARS-CoV-2 infection MESHD. Computational analysis revealed that MC can bind strongly to SARS-CoV-2 ADP Ribose Phosphatase ( NSP3 HGNC NSP3 PROTEIN) with high binding energy of -10.3 kcal/mol and to SARS-CoV-2 methyltransferase ( NSP10 PROTEIN- NSP16 PROTEIN complex) with a high binding energy of -10.4 kcal/mol. We found that MC interacts with critical residues of viral NSP3 PROTEIN NSP3 HGNC macro-domain, known to suppress host immune response, through hydrophobic interactions and occupies its active site. Furthermore, MC interacts with the critical residues of NSP10 PROTEIN- NSP16 PROTEIN complex, known to prevent innate immune detection of viral mRNA, through hydrophobic and hydrogen bond interaction and occupies the methyl group donor site. MC is also found to bind to main protease PROTEIN of SARS-CoV-2 and may potentially act as an inhibitor of the viral protease. In conclusion, MC can potentially inhibit the activity of multiple SARS-CoV-2 proteins and may accentuate the innate immune system mediated clearance of viral load resulting in improved clinic outcome in COVID-19 MESHD patients.

    A Comprehensive SARS-CoV-2 Genomic Analysis Identifies Potential Targets for Drug Repurposing

    Authors: Nithishwer Mouroug Anand; Devang Haresh Liya; Arpit Kumar Pradhan; Nitish Tayal; Abhinav Bansal; Sainitin Donakonda; Ashwin Kumar Jainarayanan

    doi:10.26434/chemrxiv.12430919.v1 Date: 2020-06-05 Source: ChemRxiv

    Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) initially reported in December 2019 in Wuhan City, China causing pneumonia-like symptoms and other respiratory tract illness. It’s higher transmission and infection rate has successfully enabled it to have a global spread over a matter of small time. With 6,529,240 cases and about 385,264 deaths, this pandemic has become a global concern with certain drugs and vaccines failing at later clinical trials. Materials and Methods: Phylogenetic Analysis, Haplotype Network, Analysis of conserved genes and population-level variants, Using conserved genes as targets for drug designing, Docking studies and Molecular Dynamics (MD) simulations to predict the stability of Drug-Ligand Complex. Results: We identified the most common haplotypes from the haplotype network and at least seven different clusters were found signifying seven different viral lineages across the globe. We studied the mutation frequency across the SARS-CoV-2 viral genome. The conserved genes and population level variants were analyzed and NSP10 PROTEIN, Nucleoprotein PROTEIN, Plpro and 3CLpro PROTEIN which were conserved at the highest threshold were used as drug targets for molecular dynamics simulations. Darifenacin, Nebivolol, Bictegravir, Alvimopan and Irbesartan are among the potential drugs which are suggested for further pre-clinical and clinical trials. Significance: This particular study provides a comprehensive targeting of the conserved genes as a novel approach for drug targeting. The conserved gene approach could also be of a big use while designing vaccines and cure. Mutations in the viral genome make the designing of the drugs a challenging task which has a higher risk of failure at later clinical trials. This approach of targeting the stable genes for drug discovery would provide a better therapeutic approach and confidence in the successive clinical trials. We also identified the global level spread of SARS-CoV-2 and mutation frequencies across the viral genome. Our study gives insights of the origin and global spread of the SARS-CoV-2. The data provided in this study can further be used by other groups to understand and combat Covid 19.

    Shortlisting Phytochemicals Exhibiting Inhibitory Activity against Major Proteins of SARS-CoV-2 through Virtual Screening

    Authors: Saranya Nallusamy; Jayakanthan Mannu; Caroline Ravikumar; Kandavelmani Angamuthu; Bharathi Nathan; Kumaravadivel Nachimuthu; Gnanam Ramasamy; Raveendran Muthurajan; Mohankumar Subbarayalu; Kumar Neelakandan

    doi:10.21203/rs.3.rs-31834/v1 Date: 2020-05-27 Source: ResearchSquare

    Severe Acute Respiratory Syndrome Corona Virus 2 MESHD (SARS-CoV-2) declared as a pandemic by WHO that has affected more than 40 lakh peoples and caused death MESHD of more than 2 lakh individuals across the globe. Limited availability of genomic information of SARS-CoV-2 and non-availability of vaccines and effective drugs are major problems responsible for the ineffective control and management of this pandemic. Several attempts have been made to explore repurposing existing drugs known for their anti-viral activities, and test the traditional herbal medicines known for their health benefiting and immune boosting activity against SARS-CoV-2.In this study, efforts were made to examine the potential of 721 phytochemicals of 37 plant species in inhibiting major protein targets namely, spike glycoprotein PROTEIN, main protease PROTEIN (MPro), NSP3 HGNC NSP3 PROTEIN, NSP9 PROTEIN, NSP15 PROTEIN, NSP10 PROTEIN- NSP16 PROTEIN and RNA dependent RNA polymerase PROTEIN of SARS-CoV-2 through virtual screening approach. Results of our experiments revealed that SARS-CoV-2 MPro shared significant dissimilarities against SARS-CoVMPro and MERS-CoVMPro indicating the need for discovering novel drugs. This study has identified the phytochemical cyanin (Zingiber officinale) exhibiting broad spectrum inhibitory activity against main proteases PROTEIN of all the three Coronaviruses. Amentoflavone, agathisflavone, catechin-7-o-gallate and chlorogeninwere shown to exhibit multi target inhibitory activity. This study has identified Mangifera indica, Anacardium occidentale, Vitex negundo, Solanum nigrum, Pedalium murex, Terminalia chebula, Azadirachta indica, Cissus quadrangularis, Clerodendrum serratum and Ocimum basilicum as potential sources of phytochemicals combating n COVID-19 MESHD. More interestingly, this study has generated evidences for the anti-viral properties of the traditional herbal formulation “Kabasura kudineer” recommended by AYUSH, a unit of Government of India. Testing of short listed phytochemicals through clinical trials will help in developing effective formulation for management of this pandemic disease. Genomic analysis of identified herbal plants will help in unravelling molecular complexity of therapeutic and anti-viral properties and will pave way for designing synthetic drugs. 

    Molecular Docking, ADME Analysis, and Estimation of MM/GBSA Binding-Free Energies of Coumarin Derivatives as Potential Inhibitors of SARS CoV-2 Receptors

    Authors: Akhilesh Kumar Maurya; Nidhi Mishra

    doi:10.21203/rs.3.rs-25847/v1 Date: 2020-04-28 Source: ResearchSquare

    Coronavirus Disease ( COVID-19 MESHD) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2). Currently, there is no specific drug for the therapy of COVID-19 MESHD. In the present study, in silico study have been done to find out possible inhibitors of SARS CoV-2. Coumarin derivatives with 2755 compounds were virtually screen against methyltransferase-stimulatory factor complex of NSP16 PROTEIN and NSP10 PROTEIN, NSP15 PROTEIN Endoribonuclease, ADP ribose phosphatase ( ADRP HGNC)of NSP3 PROTEIN NSP3 HGNC and protease enzymes of SARS CoV-2. Docked top five compounds showed good docking scores and free energy of binding with the respective receptors. ADME/T analysis of docked compound shows the docked ligands are showing drug-likeness properties.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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