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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinE (3)

ProteinN (2)

NSP6 (2)

NSP12 (2)

ComplexRdRp (2)


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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.

    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.

    Witnessing Evolution of SARS-CoV-2 through Comparative Phylogenomics: The Proximate Origin is Guangdong, not Wuhan

    Authors: Özgül Doğan; Ertan Mahir Korkmaz; Mahir Budak; Battal Çıplak; Hasan Hüseyin Başıbüyük

    id:10.20944/preprints202005.0332.v2 Date: 2020-06-21 Source: Preprints.org

    A new form of coronavirus called severe acute respiratory disease coronavirus type 2 MESHD (SARS-CoV-2) is currently causing a pandemic. A six-month evolutionary history of SARS-CoV-2 is witnessed by characterising the total genome of 821 samples using comparative phylogenomic approaches. Our analyses produced striking inclusive results that may guide scientists/professionals for the past/future of pandemic. Phylogenetic and time estimation analyses suggest the proximate origin of pandemic strain as Guangdong and the origin time as first half of September 2019, not Wuhan and December 2019, respectively. The viral genome experienced a substitution rate similar to other RNA viruses, but it is particularly high in some of the peptides encoding sequences such as leader protein, E PROTEIN gene, orf8, orf10, nsp10, N gene PROTEIN, S gene and M gene and nsp4 HGNC, while low in nsp11, orf7a PROTEIN, 3C-like proteinase, nsp9, nsp8 and endoRNase. Most strikingly, the divergence rate of amino acid sequences is high proportional to nucleotide divergence. Additionally, specific non-synonymous mutations in nsp3 HGNC and nsp6 evolved under positive selection. The exponential growth rate (r), doubling time (Td) and R0 were estimated to be 47.43 per year, 5.39 days and 2.72, respectively. Comparison of synapomorphies distinguishing the SARS-CoV-2 and the candidate ancestor bat coronavirus indicates that mutation pattern in nsp3 HGNC and S gene enabled the new strain to invade human and become a pandemic strain. We arrive at the following main conclusions: (i) six months evolution of viral genome is nearly neutral, (ii) origin of pandemic is not Wuhan and predates formal reports, (iii) although viral population is ongoing an exponential growth, the doubling time is evolving towards shortening, and (iv) divergence rate of total genome is similar to other RNA viruses, but it is prominently high in some genes while low in some others and evolution in these genes should be closely monitored as their protein products intervening to pathogenicity, virulence and immune response.

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