scholarly journals Spike independent replication of human coronavirus in bat cells

2021 ◽  
Author(s):  
Martin Linster ◽  
Marcus G Mah ◽  
Dolyce HW Low ◽  
Zhuang Yan ◽  
Jayanthi Jayakumar ◽  
...  

Bats are a likely zoonotic reservoir for a range of human pathogens including endemic human coronaviruses and SARS-CoV-2. Despite the high burden caused by these viruses, the factors required for the establishment and ongoing transmission in humans are not well understood, hampering efforts for pandemic preparedness. To help understand those adaptations required to cross the species barrier, we serially passaged endemic human coronavirus 229E isolates in a newly established Rhinolophus (horseshoe bat) kidney cell line. Here we report extensive mutations, including deletions, in the virus genome that result in the loss of spike protein expression, while maintaining the capability to infect bat cells. While we observed a loss of infectivity of human cells for all viruses with spike deletions, one isolate (2613) with an insertion that results in an early stop codon, was recovered from human cells. Deep sequencing of isolate 2613 showed that the majority population had acquired additional nucleotide insertions in the spike resulting in an additional codon that restores spike function. Spike-independent replication of coronaviruses provides an alternative route for infection of host species that don't share common cell-entry receptors.

2020 ◽  
Author(s):  
Alan T Evangelista

UNSTRUCTURED The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern. INTERNATIONAL REGISTERED REPORT RR2-doi.org/10.1101/2020.05.15.20103416


BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Andra Waagmeester ◽  
Egon L. Willighagen ◽  
Andrew I. Su ◽  
Martina Kutmon ◽  
Jose Emilio Labra Gayo ◽  
...  

Abstract Background Pandemics, even more than other medical problems, require swift integration of knowledge. When caused by a new virus, understanding the underlying biology may help finding solutions. In a setting where there are a large number of loosely related projects and initiatives, we need common ground, also known as a “commons.” Wikidata, a public knowledge graph aligned with Wikipedia, is such a commons and uses unique identifiers to link knowledge in other knowledge bases. However, Wikidata may not always have the right schema for the urgent questions. In this paper, we address this problem by showing how a data schema required for the integration can be modeled with entity schemas represented by Shape Expressions. Results As a telling example, we describe the process of aligning resources on the genomes and proteomes of the SARS-CoV-2 virus and related viruses as well as how Shape Expressions can be defined for Wikidata to model the knowledge, helping others studying the SARS-CoV-2 pandemic. How this model can be used to make data between various resources interoperable is demonstrated by integrating data from NCBI (National Center for Biotechnology Information) Taxonomy, NCBI Genes, UniProt, and WikiPathways. Based on that model, a set of automated applications or bots were written for regular updates of these sources in Wikidata and added to a platform for automatically running these updates. Conclusions Although this workflow is developed and applied in the context of the COVID-19 pandemic, to demonstrate its broader applicability it was also applied to other human coronaviruses (MERS, SARS, human coronavirus NL63, human coronavirus 229E, human coronavirus HKU1, human coronavirus OC4).


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 448
Author(s):  
Konstantina Vougogiannopoulou ◽  
Angela Corona ◽  
Enzo Tramontano ◽  
Michael N. Alexis ◽  
Alexios-Leandros Skaltsounis

The ongoing pandemic of severe acute respiratory syndrome (SARS), caused by the SARS-CoV-2 human coronavirus (HCoV), has brought the international scientific community before a state of emergency that needs to be addressed with intensive research for the discovery of pharmacological agents with antiviral activity. Potential antiviral natural products (NPs) have been discovered from plants of the global biodiversity, including extracts, compounds and categories of compounds with activity against several viruses of the respiratory tract such as HCoVs. However, the scarcity of natural products (NPs) and small-molecules (SMs) used as antiviral agents, especially for HCoVs, is notable. This is a review of 203 publications, which were selected using PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar, evaluates the available literature since the discovery of the first human coronavirus in the 1960s; it summarizes important aspects of structure, function, and therapeutic targeting of HCoVs as well as NPs (19 total plant extracts and 204 isolated or semi-synthesized pure compounds) with anti-HCoV activity targeting viral and non-viral proteins, while focusing on the advances on the discovery of NPs with anti-SARS-CoV-2 activity, and providing a critical perspective.


2020 ◽  
Vol 7 (11) ◽  
Author(s):  
Sangshin Park ◽  
Yeonjin Lee ◽  
Ian C Michelow ◽  
Young June Choe

Abstract In the context of the coronavirus disease 2019 pandemic, we aimed to systematically address the global seasonal patterns of human coronavirus (HCoV) infections. We identified relevant articles from MEDLINE, EMBASE, and CINAHL Plus as of May 11, 2020. The main outcomes were the peak months of HCoV infections each year and the months during which more than 5% of positive respiratory specimen tests were attributable to HCoV. Of 707 articles reviewed, 22 met the inclusion criteria. The annual percentage of HCoV infections reached a peak in February globally. We found a higher HCoV positivity rate among studies that tested only children (median: 5.9%, range: 0.9%–18.4%), compared with other studies of adults alone (median: 5.2%, range: 3.3%–7.1%) or the entire population (median: 1.9%, range: 0.2%–8.1%). We found the largest global peak of HCoV during the winter season, with the highest rate of positivity among children.


2020 ◽  
Vol 94 (18) ◽  
Author(s):  
Xuesen Zhao ◽  
Shuangli Zheng ◽  
Danying Chen ◽  
Mei Zheng ◽  
Xinglin Li ◽  
...  

ABSTRACT C3A is a subclone of the human hepatoblastoma HepG2 cell line with strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an effort to search for the host cellular protein(s) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection, we found that ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2), gamma-interferon-inducible lysosome/endosome-localized thiolreductase (GILT), and lymphocyte antigen 6 family member E (LY6E), the three cellular proteins identified to function in interference with virus entry, were expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of HCoV-O43. While overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection of HCoV-OC43, knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection. Moreover, we found that LY6E also efficiently restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFN-inducible transmembrane 3 (IFITM3) restriction of human coronavirus (CoV) entry, but did not compromise the effect of LY6E on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis via a mechanism distinct from other factors that modulate CoV entry. IMPORTANCE Virus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control of host innate and adaptive immune responses. In the last decade, several interferon-inducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH, and LY6E, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E was recently identified as a host factor that facilitates the entry of several human-pathogenic viruses, including human immunodeficiency virus, influenza A virus, and yellow fever virus. Identification of LY6E as a potent restriction factor of coronaviruses expands the biological function of LY6E and sheds new light on the immunopathogenesis of human coronavirus infection.


2006 ◽  
Vol 87 (5) ◽  
pp. 1203-1208 ◽  
Author(s):  
Doris Chibo ◽  
Chris Birch

Historically, coronaviruses have been recognized as a cause of minor respiratory infections in humans. However, the recent identification of three novel human coronaviruses, one causing severe acute respiratory syndrome (SARS), has prompted further examination of these viruses. Previous studies of geographically and chronologically distinct Human coronavirus 229E (HCoV-229E) isolates have found only limited variation within S gene nucleotide sequences. In contrast, analysis of the S genes of contemporary Human coronavirus OC43 variants identified in Belgium revealed two distinct viruses circulating during 2003 and 2004. Here, the S and N gene sequences of 25 HCoV-229E variants identified in Victoria, Australia, between 1979 and 2004 in patients with symptomatic infections were determined. Phylogenetic analysis showed clustering of the isolates into four groups, with evidence of increasing divergence with time. Evidence of positive selection in the S gene was also established.


2002 ◽  
Vol 76 (2) ◽  
pp. 507-516 ◽  
Author(s):  
P. S. Chin ◽  
E. Hoffmann ◽  
R. Webby ◽  
R. G. Webster ◽  
Y. Guan ◽  
...  

ABSTRACT The A/teal/Hong Kong/W312/97 (H6N1) influenza virus and the human H5N1 and H9N2 influenza viruses possess similar genes encoding internal proteins, suggesting that H6N1 viruses could become novel human pathogens. The molecular epidemiology and evolution of H6 influenza viruses were characterized by antigenic and genetic analyses of 29 H6 influenza viruses isolated from 1975 to 1981 and 1997 to 2000. Two distinct groups were identified on the basis of their antigenic characteristics. Phylogenetic analysis revealed that all H6N1 viruses isolated from terrestrial poultry in 1999 and 2000 are closely related to A/teal/Hong Kong/W312/97 (H6N1), and the nucleotide sequences of these viruses and of A/Hong Kong/156/97 (H5N1) were more than 96% homologous. The hemagglutinin (HA) of the 1999 and 2000 terrestrial viruses does not have multiple basic amino acids at the site of cleavage of HA1 to HA2; however, a unique insertion of aspartic acid in HA1 between positions 144 and 145 (H3 numbering) was found. The neuraminidase of these terrestrial H6N1 viruses has a deletion of 19 amino acids characteristic of A/Hong Kong/156/97 (H5N1). Evolutionary analysis suggested that these H6N1 viruses coevolved with A/quail/Hong Kong/G1/97-like H9N2 viruses and became more adapted to terrestrial poultry. These terrestrial 1999 and 2000 A/teal/Hong Kong/W312/97 (H6N1)-like viruses, along with the H9N2 viruses, could have been involved in the genesis of the pathogenic H5N1 influenza viruses of 1997. The presence of H6N1 viruses in poultry markets in Hong Kong that possess seven of the eight genes of the A/Hong Kong/156/97 (H5N1) virus raises the following fundamental questions relevant to influenza pandemic preparedness: could the pathogenic H5N1 virus reemerge and could the H6N1 viruses directly cross the species barrier to mammals?


2006 ◽  
Vol 80 (10) ◽  
pp. 4992-4997 ◽  
Author(s):  
Kevin M. Myles ◽  
Cindy L. H. Kelly ◽  
Jeremy P. Ledermann ◽  
Ann M. Powers

ABSTRACT The genomic RNA of an alphavirus encodes four different nonstructural proteins, nsP1, nsP2, nsP3, and nsP4. The polyprotein P123 is produced when translation terminates at an opal termination codon between nsP3 and nsP4. The polyprotein P1234 is produced when translational readthrough occurs or when the opal termination codon has been replaced by a sense codon in the alphavirus genome. Evolutionary pressures appear to have maintained genomic sequences encoding both a stop codon (opal) and an open reading frame (arginine) as a general feature of the O'nyong-nyong virus (ONNV) genome, indicating that both are required at some point. Alternate replication of ONNVs in both vertebrate and invertebrate hosts may determine predominance of a particular codon at this locus in the viral quasispecies. However, no systematic study has previously tested this hypothesis in whole animals. We report here the results of the first study to investigate in a natural mosquito host the functional significance of the opal stop codon in an alphavirus genome. We used a full-length cDNA clone of ONNV to construct a series of mutants in which the arginine between nsP3 and nsP4 was replaced with an opal, ochre, or amber stop codon. The presence of an opal stop codon upstream of nsP4 nearly doubled (75.5%) the infectivity of ONNV over that of virus possessing a codon for the amino acid arginine at the corresponding position (39.8%). Although the frequency with which the opal virus disseminated from the mosquito midgut did not differ significantly from that of the arginine virus on days 8 and 10, dissemination did began earlier in mosquitoes infected with the opal virus. Although a clear fitness advantage is provided to ONNV by the presence of an opal codon between nsP3 and nsP4 in Anopheles gambiae, sequence analysis of ONNV RNA extracted from mosquito bodies and heads indicated codon usage at this position corresponded with that of the virus administered in the blood meal. These results suggest that while selection of ONNV variants is occurring, de novo mutation at the position between nsP3 and nsP4 does not readily occur in the mosquito. Taken together, these results suggest that the primary fitness advantage provided to ONNV by the presence of an opal codon between nsP3 and nsP4 is related to mosquito infectivity.


Author(s):  
Sorush Niknamian

Background: Coronaviruses are a group of related viruses that cause diseases in mammals and birds. In humans, coronaviruses cause respiratory tract infections that can range from mild to lethal. Mild illnesses include some cases of the common cold, while more lethal varieties can cause SARS, MERS, and COVID-19. The outbreak was identified in Wuhan, China, in December 2019, declared to be a Public Health Emergency of International Concern on 30 January 2020, and recognized as a pandemic on 11 March 2020. Introduction: Coronaviruses are the subfamily Orthocoronavirinae, within the family of Coronaviridae; order Nidovirales, and realm Riboviria. They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses is approximately from 26 to 32kilobases. Coronaviruses were first discovered in the 1930s and Human coronaviruses were discovered in the 1960s. The earliest ones studied were from human patients with the common cold, which were later named human coronavirus 229E and human coronavirus OC43. Other human coronaviruses have since been identified, including SARS-CoV in 2003, HCoV NL63 in 2004, HKU1 in 2005, MERS-CoV in 2012, and SARS-CoV-2 in 2019. Most of these have involved serious respiratory tract infections. Discussions & Results: Based on our multidisciplinary research, we have found the major cause and some treatments methods for fighting this powerful pathogen. The prime cause of COVID-19 is pushing the mitochondrial to lose MMP. A loss of the MMP by any mechanism leads to functional and structural collapse of the mitochondria and cell death. Mitophagy plays an important role in maintaining mitochondrial homeostasis, but can also eliminate healthy mitochondria in cases such as cell starvation, viral invasion, and erythroid cell differentiation. The mitochondrial fusion and fission are highly dynamic. Viruses specially COVID-19, interfere with these processes to distort mitochondrial dynamic to facilitate their proliferation. Thus, interfering with these processes promotes the interference of different cellular signaling pathways. The severe acute respiratory syndrome coronavirus (SARS-CoV) escapes the innate immune response by translocating its ORF-9b to mitochondria and promotes proteosomal degradation of dynamin-like protein (Drp1) leading to mitochondrial fission. We also researched on Ultrasonic Energy to destroy the virus which leads to positive results but it needs more future research. The most destructive way of viruses is to enhance Reactive Oxygen Species (ROS) and free radicals in human contaminated cell which cause inflammation in a host cell. ELF-EMF converts free radicals into less active molecules and eliminates them into two pathways which have been discussed in the discussion part. Using ELF-EMF affects the second pathway that relies on the activity of the catalase and superoxide dismutase enzymes which is the most effective pathway. For the best result of treatment, is the use of lowfrequency magnetic fields (LFMF) plus EMF-ELF which penetrate into deeper tissues, cells and mitochondria. We also have gone through many researches since 1920 and found if we emit the frequency as the same frequency of COVID-19, can cause resonance in the virus and destroy it. So we measured the SARS-CoV-2 frequency by Cyclotron and calculated the frequencyof the virus is 30 KHz-500 KHz. Conclusion: COVID-19 (SARS-CoV-2) is one of the most complex viruses which have been discovered since 2020. Until today, there has been no Antiviral Drug which can be useful in the treatment of this infectious disease has been discovered till today. COVID-19 genomic sequence containing SARS-CoV, MERS-CoV and Influenza A. Therefore; there is a high possibility of continuing COVID-19 even in summer. To gain the best result in treatment, we should use low-frequency magnetic fields (LFMF) plus EMF which penetrate into deeper tissues, cells and mitochondria in order to reduce ROS and Inflammation. In order to destroy SARS-CoV-2 virus in environment and also in infected individuals, we should use ELF-EMF plus LFMF. We also have gone through many researches since 1920 and found if we emit the frequency as the same frequency of COVID-19, it can cause resonance in the virus and destroy it. So we measured the SARS-CoV-2 frequency by Cyclotron and calculated the frequency of the virus that id is 30 KHz-500 KHz. The differences in the frequencies are due to the size of the virus which is from 26 to 32 Kilobases.


2020 ◽  
Author(s):  
Alan T Evangelista

The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern.


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