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    Unravelling Vitamins as Wonder Molecules for Covid-19 MESHD Management via Structure-based Virtual Screening

    Authors: Medha Pandya; Sejal Shah; Dhanalakshmi Menamadathil; Ayushman Gadnayak; Tanzil Juneja; Amisha Patel; Kajari Das; Jayashankar Das

    doi:10.21203/rs.3.rs-144177/v1 Date: 2021-01-09 Source: ResearchSquare

    The emergence situation of coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic has realised the global scientific communities to develop strategies for immediate priorities and long-term approaches for utilization of existing knowledge and resources which can be diverted to pandemic preparedness planning. Lack of proper vaccine candidate and therapeutic management has accelerated the researchers to repurpose the existing drugs with known preclinical and toxicity MESHD profiles, which can easily enter Phase 3 or 4 or can be used directly in clinical settings. We focused to justify even exploration of supplements, nutrients and vitamins to dampen the disease burden of the current pandemic may play a crucial role for its management. We have explored structure based virtual screening of 15 vitamins against non-structural ( NSP3 HGNC NSP3 PROTEIN, NSP5 PROTEIN NSP5 HGNC, ORF7a PROTEIN, NSP12 PROTEIN, ORF3a PROTEIN), structural (Spike & Hemagglutinin esterase) and host protein furin HGNC. The in silico analysis exhibited that vitamin B12, Vitamin B9, Vitamin D3 determined suitable binding while vitamin B15 manifested remarkable H-bond interactions with all targets. Vitamin B12 bestowed the lowest energies with human furin HGNC and SARS-COV-2 RNA dependent RNA polymerase PROTEIN. Furin HGNC mediated cleavage of the viral spike glycoprotein PROTEIN is directly related to enhanced virulence of SARS-CoV-2. In contrast to these, vitamin B12 showed zero affinity with SARS-CoV-2 spike PROTEIN protein. These upshots intimate that Vitamin B12 could be the wonder molecule to shrink the virulence by hindering the furin HGNC mediated entry of spike to host cell. These identified molecules may effectively assist in SARS-CoV-2 therapeutic management to boost the immunity by inhibiting the virus imparting relief in lung inflammation MESHD.

    Early Onset Favipiravir Saves Lives

    Authors: Ercan KARATAS; Lacin Aksoy; Pinar Elbir Kilic; Arzu Dogru; Ersin Ozaslan

    doi:10.21203/rs.3.rs-142868/v1 Date: 2021-01-07 Source: ResearchSquare

    Background Favipiravir, an antiviral recommended for use in patients with tachypnea MESHD (respiratory rate 30 / min) in COVID-19 MESHD pneumonia MESHD, with SpO2 level below 90% in room air and with bilateral diffuse pneumonia MESHD on chest X-ray or tomography, or patients with treatment-resistant fever MESHD, is a new type of RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN) inhibitor. After the administration of Favipiravir, it contributed significantly to reducing mortality in patients with severe COVID-19 MESHD positive disease. We performed this study to determine the start time in Favipiravir's covid pneumonia.Material MESHD and Method: We evaluated the effect of a total of 5 days of oral treatment as a 2 × 1600 mg loading dose and a 2 × 600 mg maintenance dose of Favipiravir added to the standard COVID-19 MESHD treatment received by patients with laboratory-radiology-clinical findings who have advanced or severe COVID 19 pneumonia MESHD.Results 180 patients hospitalized at Tuzla State Hospital and given Favipiravir treatment between 20/3/2020 and 30/5/2020 were examined. As of hospitalization, 17 of 101 patients (17%) who were given Favipiravir treatment in ≤ 3 days died, 30 of 79 patients (38%) who were given Favipiravir treatment for in > 3 days died (p:0.002). 33 of 47 patients (70%) who died were > 65 years old. Only 5 of the 47 (11%) patients who died had no comorbid disease. 35 had two or more comorbid diseases.Conclusion Patients with radiological findings indicating that COVID-19 MESHD will be severe and laboratory findings at the time of the first 3 days should be initiated with an effective dose of Favipiravir treatment without waiting for the clinical worsening.

    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.

    Major Concerns on the Identification of Bat Coronavirus Strain RaTG13 and Quality of Related Nature Paper

    Authors: xiaoxu lin; Shizhong Chen

    id:10.20944/preprints202006.0044.v1 Date: 2020-06-05 Source: Preprints.org

    A recent manuscript (Zhou, P. et al. “ A pneumonia MESHD outbreak associated with a new coronavirus of probable bat origin”, Nature 579, 270–273 (2020). https://doi.org/10.1038/s41586-020-2012-7) from Wuhan Institute of Virology claimed the identification of a bat coronavirus, RaTG13, which showed 96.2% genome homology with SARS-CoV-2. In this paper, we raise the puzzling observations surrounding the identification, characterization, unique genome features of this RaTG13 strain, as well as its 100% nucleotide identity in partial RdRp PROTEIN gene with another bat coronavirus strain BtCoV/4991. And the paper presented premature hypothesis of potential bat origin of SARS-CoV-2 while RaTG13 strain was not successfully isolated. We also present the concerns on the methodology, data quality and experiment procedures described in this paper. We call for the authors to provide additional data, to share related samples to be verified and further characterized by other scientists.

    Understanding the Origin of ‘BatCoVRaTG13’, a Virus Closest to SARS-CoV-2

    Authors: Monali C. Rahalkar; Rahul A. Bahulikar

    id:202005.0322/v2 Date: 2020-05-24 Source: Preprints.org

    Genomic analysis indicates that SARS-CoV-2 is most related to RaTG13, a beta corona virus derived from bats by 96% 1. At present, RaTG13 is only available on the public database in the form of a genome sequence. The genome of RaTG13 (MN996532.1) was sequenced from the RNA of a bat faecal swab collected in 2013 from Yunnan, China, however the exact location is not mentioned. Since RaTG13 is one of the main supports for SARS-CoV-2 to have a natural origin, it is of utmost importance to understand the sample location. RNA dependent RNA polymerase PROTEIN ( RdRp PROTEIN) sequence of RaTG13 shows that it is 100% similar to that of bat corona virus BtCoV/4991 and 98.7-98.9% similar to SARS-CoV-2 RdRp MESHD RdRp PROTEIN 2. BtCoV/4991 was described to be a SARS-like (SL-) corona virus from bat faeces sampled in an abandoned mine from Mojiang 2. Both the publications 1,2 are authored by Dr. Zheng-li Shi (Z-L Shi), who is described as the bat woman of China 3. However, BtCoV/4991 has not been mentioned by Zhou et al 2020 1 where novel corona virus was first described. Based on the RdRp PROTEIN sequence similarities, similarities in sample collection dates, sample locations, and the fact that RaTG13 is mentioned synonymous to BtCoV/4991 on the Chinese bat database, it is predicted that RaTG13 and BtCoV/4991 originate from the same sample. The sample, bat faecal swab was collected in 2013 from an abandoned mineshaft in Mojiang by Dr. Shi and her work group. In 2012, in a Mojiang mineshaft, six mine workers suffered from atypical pneumonia MESHD and three of them died. These workers were engaged in the work of clearing debris from a mineshaft which had a lot of bats and bat faeces 3,4. A detailed health investigation indicated that the miners suffered from atypical pneumonia MESHD mostly of the viral origin 4. Therefore, in the light of the present Covid-19 MESHD caused by SARS-CoV-2, the fact that its phylogenetic neighbour RaTG13 originated from bat faeces collected from a mineshaft, which was also the origin of pneumonia-like disease MESHD in miners in 2012, should be noted.

    Decoding the structure of RNA-dependent RNA-polymerase PROTEIN ( RdRp PROTEIN), understanding the ancestral relationship and dispersion pattern of 2019 Wuhan Coronavirus

    Authors: Abbas Khan; Mazhar Khan; Shoaib Saleem; Zainib Babar; Arif Ali; Abdul Aziz Khan; Zain Sardar; Fahad Hamayun; Syed Shujait Ali; Dong-Qing Wei

    doi:10.21203/rs.3.rs-25334/v1 Date: 2020-04-25 Source: ResearchSquare

    Most recently, an outbreak of severe pneumonia MESHD caused by the infection of 2019-nCoV, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins ( nsp HGNC) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. Since there is no crystallographic structure of RdRp PROTEIN is available, so, here, we present the 3-dimensional structure of the 2019-nCoV nsp12 polymerase using a computational approach. nsp12 of 2019-nCoV possesses an architecture common to all viral polymerases as well as a large N-terminal extension. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into nsp12 polymerase catalysis and fidelity, and acts as a template for the design of novel antiviral therapeutics. Besides, the experimental structure could reveal the organization in a more sophisticated way. Furthermore, the ancestral state reconstruction suggests the possible evolution of nCoV in Wuhan China and its dispersal to the USA. The result of our analyses postulates the possible dispersal of nCoV from the USA and Shenzhen back to Wuhan. This disclosing of valuable knowledge regarding the 3D structure of 2019-nCoV nsp12 architecture, ancestral relation, and dispersion pattern could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements.

    Suppression of COVID-19 MESHD outbreak in the municipality of Vo, Italy

    Authors: Enrico Lavezzo; Elisa Franchin; Constanze Ciavarella; Gina Cuomo-Dannenburg; Luisa Barzon; Claudia Del Vecchio; Lucia Rossi; Riccardo Manganelli; Arianna Loregian; Nicolò Navarin; Davide Abate; Manuela Sciro; Stefano Merigliano; Ettore Decanale; Maria Cristina Vanuzzo; Francesca Saluzzo; Francesco Onelia; Monia Pacenti; Saverio Parisi; Giovanni Carretta; Daniele Donato; Luciano Flor; Silvia Cocchio; Giulia Masi; Alessandro Sperduti; Lorenzo Cattarino; Renato Salvador; Katy A.M. Gaythorpe; - Imperial College London COVID-19 Response Team; Alessandra R Brazzale; Stefano Toppo; Marta Trevisan; Vincenzo Baldo; Christl A. Donnelly; Neil M. Ferguson; Ilaria Dorigatti; Andrea Crisanti

    doi:10.1101/2020.04.17.20053157 Date: 2020-04-18 Source: medRxiv

    On the 21st of February 2020 a resident of the municipality of Vo, a small town near Padua, died of pneumonia MESHD due to SARS-CoV-2 infection MESHD. This was the first COVID-19 MESHD death detected in Italy since the emergence of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days. We collected information on the demography, clinical presentation, hospitalization, contact network and presence of SARS-CoV-2 infection MESHD in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo at two consecutive time points. On the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI) 2.1-3.3%). On the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% CI 0.8-1.8%). Notably, 43.2% (95% CI 32.2-54.7%) of the confirmed SARS-CoV-2 infections MESHD detected across the two surveys were asymptomatic. The mean serial interval was 6.9 days (95% CI 2.6-13.4). We found no statistically significant difference in the viral load (as measured by genome equivalents inferred from cycle threshold data) of symptomatic versus asymptomatic infections (p-values 0.6 and 0.2 for E and RdRp PROTEIN genes, respectively, Exact Wilcoxon-Mann-Whitney test). Contact tracing of the newly infected cases and transmission chain reconstruction revealed that most new infections in the second survey were infected in the community before the lockdown or from asymptomatic infections living in the same household. This study sheds new light on the frequency of asymptomatic SARS-CoV-2 infection MESHD and their infectivity (as measured by the viral load) and provides new insights into its transmission dynamics, the duration of viral load detectability and the efficacy of the implemented control measures.

    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.

    Comparative Genomic Analysis of Rapidly Evolving SARS CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution

    Authors: Roshan Kumar; Helianthous Verma; Nirjara Singhvi; Utkarsh Sood; Vipin Gupta; Mona Singh; Rashmi Sharma; Princy Hira; Shekhar Nagar; Chandni Talwar; Namita Nayyar; Shailly Anand; Charu Dogra Rawat; Mansi Verma; Ram Kishan Negi; Yogendra Singh; Rup Lal

    doi:10.1101/2020.03.25.006213 Date: 2020-03-30 Source: bioRxiv

    The Coronavirus Disease-2019 ( COVID-19 MESHD) that started in Wuhan, China in December 2019 has spread worldwide emerging as a global pandemic. The severe respiratory pneumonia MESHD caused by the novel SARS-CoV-2 has so far claimed more than 60,000 lives and has impacted human lives worldwide. However, as the novel SARS-CoV-2 displays high transmission rates, their underlying genomic severity is required to be fully understood. We studied the complete genomes of 95 SARS-CoV-2 strains from different geographical regions worldwide to uncover the pattern of the spread of the virus. We show that there is no direct transmission pattern of the virus among neighboring countries suggesting that the outbreak is a result of travel of infected humans to different countries. We revealed unique single nucleotide polymorphisms (SNPs) in nsp13-16 (ORF1b polyprotein) and S-Protein PROTEIN within 10 viral isolates from the USA. These viral proteins are involved in RNA replication, indicating highly evolved viral strains circulating in the population of USA than other countries. Furthermore, we found an amino acid addition in nsp16 (mRNA cap-1 methyltransferase) of the USA isolate (MT188341) leading to shift in amino acid frame from position 2540 onwards. Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA HGNC, TGF-{beta} HGNC, SOCS3 HGNC, STAT3 HGNC, JAK1/2, SMAD3 HGNC, BCL2 HGNC, CAV1 HGNC & SPECC1 HGNC) are manipulated by the viral proteins ( nsp2 HGNC, PL-PRO, N-protein PROTEIN, ORF7a PROTEIN, M-S- ORF3a PROTEIN complex, nsp7-nsp8-nsp9- RdRp complex PROTEIN) for mediating host immune evasion. Thus, the replicative machinery of SARS-CoV-2 is fast evolving to evade host challenges which need to be considered for developing effective treatment strategies.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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