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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (52)

ComplexRdRp (52)

NSP5 (18)

NSP3 (15)

ORF3a (8)


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SARS-CoV-2 Proteins
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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.

    SARS-CoV-2 genome analysis of strains in Pakistan reveals GH, S and L clade strains at the start of the pandemic

    Authors: Najia K Ghanchi; Kiran I Masood; Asghar Nasir; Waqasuddin Khan; Syed H Abidi; Saba Shahid; Syed F Mahmood; Akbar R Kanji; Safina A Razzak; Zeeshan Ansar; Nazneen Islam; Mohammad B Dharejo; Zahra Hasan; Rumina Hasan

    doi:10.1101/2020.08.04.234153 Date: 2020-08-04 Source: bioRxiv

    ObjectivesPakistan has a high infectious disease burden with about 265,000 reported cases of COVID-19 MESHD. We investigated the genomic diversity of SARS-CoV-2 strains and present the first data on viruses circulating in the country. MethodsWe performed whole-genome sequencing and data analysis of SARS-CoV-2 eleven strains isolated in March and May. ResultsStrains from travelers clustered with those from China, Saudi Arabia, India, USA and Australia. Five of eight SARS-CoV-2 strains were GH clade with Spike glycoprotein PROTEIN D614G, Ns3 HGNC gene Q57H, and RNA dependent RNA polymerase PROTEIN ( RdRp PROTEIN) P4715L mutations. Two were S ( ORF8 PROTEIN L84S and N S202N) and three were L clade and one was an I clade strain. One GH and one L strain each displayed Orf1ab L3606F indicating further evolutionary transitions. ConclusionsThis data reveals SARS-CoV-2 strains of L, G, S and I have been circulating in Pakistan from March, at the start of the pandemic. It indicates viral diversity regarding infection in this populous region. Continuing molecular genomic surveillance of SARS-CoV-2 in the context of disease severity will be important to understand virus transmission patterns and host related determinants of COVID-19 MESHD in Pakistan.

    SARS-CoV-2 and miRNA-like inhibition power

    Authors: Jacques Demongeot; Hervé Seligmann

    id:2008.00126v1 Date: 2020-07-31 Source: arXiv

    (1) Background: RNA viruses and especially coronaviruses could act inside host cells not only by building their own proteins, but also by perturbing the cell metabolism. We show the possibility of miRNA-like inhibitions by the SARS-CoV-2 concerning for example the hemoglobin and type I interferons syntheses, hence highly perturbing oxygen distribution in vital organs and immune response as described by clinicians; (2) Methods: We compare RNA subsequences of SARS-CoV-2 protein S MESHD protein S PROTEIN and RNA-dependent RNA polymerase PROTEIN genes to mRNA sequences of beta-globin and type I interferons; (3) Results: RNA subsequences longer than eight nucleotides from SARS-CoV-2 genome could hybridize subsequences of the mRNA of beta-globin and of type I interferons; (4) Conclusions: Beyond viral protein production, Covid-19 MESHD might affect vital processes like host oxygen transport and immune response.

    Identification of novel mutations in SARS-COV-2 isolates from Turkey

    Authors: Shazia Rehman; Tariq Mahmood; Ejaz Aziz; Riffat Batool

    doi:10.21203/rs.3.rs-51012/v1 Date: 2020-07-30 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), originally emerged from Wuhan, has caused an unprecedented worldwide pandemic in the first half of 2020. Since the first report of SARS-CoV-2 on March 10th, 2020 in Turkey, more than 150,000 people in the country have been infected with this virus. In this study, a total of 80 genomic virulent strains from Turkey which were uploaded in NCBI and GISAID database were analyzed with other genomic sequences from different countries with the aim to characterize notable genomic features of SARS-CoV-2 and to identify some novel mutations. Consistent with other studies, the combination of variants at positions C3037T, C14408T and A23403G were most common mutations (73%), that exist together in isolates from Turkey. Our secondary structure prediction analysis also highlighted 11 unique non-substitutional mutations from viral SARS-COV-2 isolates of Turkey in different regions such as in spike (S) protein PROTEIN and non-structural proteins (Nsp2, Nsp3, NSP4 PROTEIN, and NSP12 PROTEIN/ RdRP PROTEIN). Of these 11 mutations, nine of them have been found to be involved in structural alterations at different sites. 3/9 mutants (A771V, T1238I and G1251V) cause alteration in structure of S protein PROTEIN, while the rest of them induces structural changes in Nsp2 (A206T, R207C, T265I), Nsp3 (A1824V), Nsp4 (M2796I) and NSP12 PROTEIN (A4489V). These mutations identified here might have significant functional implications that needs to be addressed for future studies in the context of vaccine engineering and therapeutic interventions. Moreover, transmission and phylogenetic analysis revealed multiple independent sources of introductions for infection of hCovs in Turkey and close phylogenetic relationship of Turkish strains with Saudi strains.

    The genetic variants analysis of circulating SARS-CoV-2 in Bangladesh.

    Authors: Abu Sayeed Mohammad Mahmud; Tarannum Taznin; Md. Murshed Hasan Sarkar; Mohammad Samir Uzzaman; Eshrar Osman; Md. Ahasan Habib; Shahina Akter; Tanjina Akhter Banu; Barna Goswami; Iffat Jahan; Md. Saddam Hossain; Md. Salim Khan

    doi:10.1101/2020.07.29.226555 Date: 2020-07-29 Source: bioRxiv

    Genomic mutation of the virus may impact the viral adaptation to the local environment, their transmission, disease manifestation, and the effectiveness of existing treatment and vaccination. The objectives of this study were to characterize genomic variations, non-synonymous amino acid substitutions, especially in target proteins, mutation events per samples, mutation rate, and overall scenario of coronaviruses across the country. To investigate the genetic diversity, a total of 184 genomes of virus strains sampled from different divisions of Bangladesh with sampling dates between the 10th of May 2020 and the 27th of June 2020 were analyzed. To date, a total of 634 mutations located along the entire genome resulting in non-synonymous 274 amino acid substitutions in 22 different proteins were detected with nucleotide mutation rate estimated to be 23.715 substitutions per year. The highest non-synonymous amino acid substitutions were observed at 48 different positions of the papain-like protease PROTEIN ( nsp3 HGNC). Although no mutations were found in nsp7, nsp9, nsp10, and nsp11, yet orf1ab accounts for 56% of total mutations. Among the structural proteins, the highest non-synonymous amino acid substitution (at 36 positions) observed in spike proteins PROTEIN, in which 9 unique locations were detected relative to the global strains, including 516E>Q in the boundary of the ACE2 HGNC binding region. The most dominated variant G614 (95%) based in spike protein PROTEIN is circulating across the country with co-evolving other variants including L323 (94%) in RNA dependent RNA polymerase PROTEIN ( RdRp PROTEIN), K203 (82%) and R204 (82%) in nucleocapsid, and F120 (78%) in NSP2 PROTEIN NSP2 HGNC. These variants are mostly seen as linked mutations and are part of a haplotype observed in Europe. Data suggest effective containment of clade G strains (4.8%) with sub-clusters GR 82.4%, and GH clade 6.4%. HighlightsO_LIWe have sequenced 137 and analyzed 184 whole-genomes sequences of SARS-CoV-2 strains from different divisions of Bangladesh. C_LIO_LIA total of 634 mutation sites across the SARS-CoV-2 genome and 274 non-synonymous amino acid substitutions were detected. C_LIO_LIThe mutation rate of SARS-CoV-2 estimated to be 23.715 nucleotide substitutions per year. C_LIO_LINine unique variants were detected based on non-anonymous amino acid substitutions in spike protein PROTEIN relative to the global SARS-CoV-2 strains. C_LI

    SARS-CoV2 genome analysis of Indian isolates and molecular modelling of D614G mutated spike protein PROTEIN with TMPRSS2 depicted its enhanced interaction and virus infectivity

    Authors: Sunil Raghav; Arup Ghosh; Jyotirmayee Turuk; Sugandh Kumar; Atimukta Jha; Swati Madhulika; Manasi Priyadarshini; Viplov K Biswas; P. Sushree Shyamli; Bharati Singh; Neha Singh; Deepika Singh; Avula Kiran; Shuchi Smita; Jyotsnamayee Sabat; Debdutta Bhattacharya; Rupesh Dash; Shantibhushan Senapati; Tushar K Beuria; Rajeeb Swain; Soma Chattopadhyay; Gulam Hussain Syed; Anshuman Dixit; Punit Prasad; Sanghamitra Pati; Ajay Parida

    doi:10.1101/2020.07.23.217430 Date: 2020-07-23 Source: bioRxiv

    COVID-19 MESHD that emerged as a global pandemic is caused by SARS-CoV-2 virus. The virus genome analysis during disease spread reveals about its evolution and transmission. We did whole genome sequencing of 225 clinical strains from the state of Odisha in eastern India using ARTIC protocol-based amplicon sequencing. Phylogenetic analysis identified the presence of all five reported clades 19A, 19B, 20A, 20B and 20C in the population. The analyses revealed two major routes for the introduction of the disease in India i.e. Europe and South-east Asia followed by local transmission. Interestingly, 19B clade was found to be much more prevalent in our sequenced genomes (17%) as compared to other genomes reported so far from India. The haplogroup analysis for clades showed evolution of 19A and 19B in parallel whereas the 20B and 20C appeared to evolve from 20A. Majority of the 19A and 19B clades were present in cases that migrated from Gujarat state in India suggesting it to be one of the major initial points of disease transmission in India during month of March and April. We found that with the time 20A and 20B clades evolved drastically that originated from central Europe. At the same time, it has been observed that 20A and 20B clades depicted selection of four common mutations i.e. 241 C>T (5UTR), P323L in RdRP PROTEIN, F942F in NSP3 PROTEIN and D614G in the spike protein PROTEIN. We found an increase in the concordance of G614 mutation evolution with the viral load in clinical samples as evident from decreased Ct value of spike and Orf1ab gene in qPCR. Molecular modelling and docking analysis identified that D614G mutation enhanced interaction of spike with TMPRSS2 protease, which could impact the shedding of S1 domain and infectivity of the virus in host cells.

    Dissemination and co-circulation of SARS-CoV2 subclades exhibiting enhanced transmission associated with increased mortality in Western Europe and the United States

    Authors: Yuan Hu; Lee W Riley

    doi:10.1101/2020.07.13.20152959 Date: 2020-07-15 Source: medRxiv

    Mechanisms underlying the acute respiratory distress syndrome MESHD ( ARDS MESHD)-like clinical manifestations leading to deaths in patients who develop COVID-19 MESHD remain uncharacterized. While multiple factors could influence these clinical outcomes, we explored if differences in transmissibility and pathogenicity of SARS-CoV2 variants could contribute to these terminal clinical consequences of COVID-19 MESHD. We analyzed 34,412 SARS-CoV2 sequences deposited in the Global Initiative for Sharing All Influenza Data (GISAID) SARS-CoV2 sequence database to determine if regional differences in circulating strain variants correlated with increased mortality in Europe, the United States, and California. We found two subclades descending from the Wuhan HU-1 strain that rapidly became dominant in Western Europe and the United States. These variants contained nonsynonymous nucleotide mutations in the Orf1ab segment encoding RNA-dependent RNA polymerase PROTEIN (C14408T), the spike protein PROTEIN gene (A23403G), and Orf1a PROTEIN (G25563T), which resulted in non-conservative amino acid substitutions P323L, D614G, and Q57H, respectively. In Western Europe, the A23403G-C14408T subclade dominated, while in the US, the A23403G-C14408T-G25563T mutant became the dominant strain in New York and parts of California. The high cumulative frequencies of both subclades showed inconsistent but significant association with high cumulative CFRs in some of the regions. When the frequencies of the subclades were analyzed by their 7-day moving averages across each epidemic, we found co-circulation of both subclades to temporally correlate with peak mortality periods. We postulate that in areas with high numbers of these co-circulating subclades, a person may get serially infected. The second infection may trigger a hyperinflammatory response similar to the antibody-dependent enhancement (ADE) response, which could explain the ARDS MESHD-like manifestations observed in people with co-morbidity, who may not mount sufficient levels of neutralizing antibodies against the first infection. Further studies are necessary but the implication of such a mechanism will need to be considered for all current COVID-19 MESHD vaccine designs.

    Comprehensive analysis of genomic diversity of SARS-CoV-2 in different geographic regions of India: An endeavour to classify Indian SARS-CoV-2 strains on the basis of co-existing mutations

    Authors: Rakesh Sarkar; Suvrotoa Mitra; Pritam Chandra; Priyanka Saha; Anindita Banerjee; Shanta Dutta; Mamta Chawla-Sarkar

    doi:10.1101/2020.07.14.203463 Date: 2020-07-15 Source: bioRxiv

    Accumulation of mutations within the genome is the primary driving force for viral evolution within an endemic setting. This inherent feature often leads to altered virulence, infectivity and transmissibility as well as antigenic shift to escape host immunity, which might compromise the efficacy of vaccines and antiviral drugs. Therefore, we aimed at genome-wide analyses of circulating SARS-CoV-2 viruses for the emergence of novel co-existing mutations and trace their spatial distribution within India. Comprehensive analysis of whole genome sequences of 441 Indian SARS-CoV-2 strains revealed the occurrence of 33 different mutations, 21 being distinctive to India. Emergence of novel mutations were observed in S glycoprotein PROTEIN (7/33), NSP3 HGNC NSP3 PROTEIN (6/33), RdRp PROTEIN/ NSP12 PROTEIN (4/33), NSP2 PROTEIN NSP2 HGNC (2/33) and N (2/33). Non-synonymous mutations were found to be 3.4 times more prevalent than synonymous mutations. We classified the Indian isolates into 22 groups based on the co-existing mutations. Phylogenetic analyses revealed that representative strain of each group divided themselves into various sub-clades within their respective clades, based on the presence of unique co-existing mutations. India was dominated by A2a clade (55.60%) followed by A3 (37.38%) and B (7%), but exhibited heterogeneous distribution among various geographical regions. The A2a clade mostly predominated in East India, Western India and Central India, whereas A3 clade prevailed in South and North India. In conclusion, this study highlights the divergent evolution of SARS-CoV-2 strains and co-circulation of multiple clades in India. Monitoring of the emerging mutations would pave ways for vaccine formulation and designing of antiviral drugs.

    RNA-Dependent RNA Polymerase PROTEIN and Spike Protein PROTEIN Mutant Variants of SARS-CoV-2 Predominate in Severely Affected COVID-19 MESHD Patients

    Authors: Subrata K. Biswas; Sonchita R. Mudi

    id:10.20944/preprints202007.0251.v1 Date: 2020-07-12 Source: Preprints.org

    The severity of coronavirus disease 2019 MESHD ( COVID-19 MESHD), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), greatly varies from patient to patient. In the present study, we explored and compared mutation profiles of SARS-CoV-2 isolated from mildly affected and severely affected COVID-19 MESHD patients in order to explore any relationship between mutation profile and disease severity. Genomic sequences of SARS-CoV-2 were downloaded from GISAID database. With the help of Genome Detective Coronavirus Typing Tool, genomic sequences were aligned with the Wuhan seafood market pneumonia MESHD virus reference sequence and all the mutations were identified. Distribution of mutant variants was then compared between mildly and severely affected groups. Among the numerous mutations detected, 14,408C>T and 23,403A>G mutations resulting in RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN) P323L and spike protein PROTEIN D614G mutations, respectively, were found predominantly in severely affected group (>82%) compared with mildly affected group (<46%, p<0.001). The 241C>T mutation in the non-coding region of the genome was also found predominantly in severely affected group. The 3,037C>T, a silent mutation, also appeared in relatively high frequency in severely affected group. We concluded that RdRp PROTEIN P323L and spike protein PROTEIN D614G mutations predominate in severely affected COVID-19 MESHD patients. Further studies will be required to explore whether these mutations have any impact on the severity of COVID-19 MESHD.

    COVID-19 MESHD COVID-19 MESHD Pandemic: Insights into Structure, Function, and hACE2 HGNC Receptor Recognition by SARS-CoV-2

    Authors: Anshumali Mittal; Kavyashree Manjunath; Rajesh Kumar Ranjan; Sandeep Kaushik; Sujeet Kumar; Vikash Verma

    id:10.20944/preprints202005.0260.v2 Date: 2020-07-10 Source: Preprints.org

    SARS-CoV-2 is a newly emerging, highly transmissible, and pathogenic coronavirus in humans, which has caused global public health emergency and economic crisis. To date, millions of infections and thousands of deaths have been reported worldwide, and the numbers continue to rise. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism through which this virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor binding domain of the spike glycoprotein PROTEIN (S) to recognize ACE2 HGNC receptors on the human cells; this initiates host cell entry by promoting viral-host cell membrane fusion through large scale conformational changes in the S protein PROTEIN. Receptor recognition and fusion are critical and essential steps of viral infections MESHD and are key determinants of the viral host range and cross-species transmission. In this review, we summarize the current knowledge on the origin and evolution of SARS-CoV-2 and the roles of key viral factors. We discuss the RNA dependent RNA polymerase PROTEIN structure of SARS-CoV-2, its significance in drug discovery, and explain the receptor recognition mechanisms of coronaviruses. We provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins MESHD S proteins PROTEIN, receptor-binding specificity, and discuss the differences in their antigenicity based on biophysical and structural characteristics.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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