scholarly journals Independent infections of porcine deltacoronavirus among Haitian children

Nature ◽  
2021 ◽  
Author(s):  
John A. Lednicky ◽  
Massimiliano S. Tagliamonte ◽  
Sarah K. White ◽  
Maha A. Elbadry ◽  
Md. Mahbubul Alam ◽  
...  
Keyword(s):  
Febrile Illness ◽  
Cell Receptor ◽  
Receptor Binding Domain ◽  
Mutational Signature ◽  
Host Cell Receptor ◽  
The Family ◽  
Genes Encoding ◽  
Animal Contact ◽  
Human Infections ◽  
Animal Reservoirs

AbstractCoronaviruses have caused three major epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. In each case, the emergence of coronavirus in our species has been associated with zoonotic transmissions from animal reservoirs1,2, underscoring how prone such pathogens are to spill over and adapt to new species. Among the four recognized genera of the family Coronaviridae, human infections reported so far have been limited to alphacoronaviruses and betacoronaviruses3–5. Here we identify porcine deltacoronavirus strains in plasma samples of three Haitian children with acute undifferentiated febrile illness. Genomic and evolutionary analyses reveal that human infections were the result of at least two independent zoonoses of distinct viral lineages that acquired the same mutational signature in the genes encoding Nsp15 and the spike glycoprotein. In particular, structural analysis predicts that one of the changes in the spike S1 subunit, which contains the receptor-binding domain, may affect the flexibility of the protein and its binding to the host cell receptor. Our findings highlight the potential for evolutionary change and adaptation leading to human infections by coronaviruses outside of the previously recognized human-associated coronavirus groups, particularly in settings where there may be close human–animal contact.

scholarly journals Emergence of porcine delta-coronavirus pathogenic infections among children in Haiti through independent zoonoses and convergent evolution

2021 ◽  
Author(s):  
John A Lednicky ◽  
Massimiliano S Tagliamonte ◽  
Sarah K White ◽  
Maha A. Elbadry ◽  
Md Mahbubul Alam ◽  
...  
Keyword(s):  
Convergent Evolution ◽  
Febrile Illness ◽  
Cell Receptor ◽  
Receptor Binding Domain ◽  
Host Cell Receptor ◽  
The Family ◽  
Human Infections ◽  
First Time ◽  
Animal Reservoirs

Coronaviruses have caused three major epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. In each case, coronavirus emergence in our species has been associated with zoonotic transmissions from animal reservoirs, underscoring how prone such pathogens are to spill over and adapt to new species. Among the four recognized genera of the family Coronaviridae (Alphacoronavirus, Betacoronavirus, Deltacoronavirus, Gammacoronavirus), human infections reported to date have been limited to alpha and betacoronaviruses. We identify, for the first time, porcine deltacoronavirus (PDCoV) strains in plasma samples of three Haitian children with acute undifferentiated febrile illness. Genomic and evolutionary analyses reveal that human infections were the result of at least two independent zoonoses of distinct viral lineages that acquired the same mutational signature in the nsp15 and the spike glycoprotein genes by convergent evolution. In particular, structural analysis predicts that one of the changes in the Spike S1 subunit, which contains the receptor-binding domain, may affect flexibity of the protein and binding to the host cell receptor. Our findings not only underscore the ability of deltacoronaviruses to adapt and potentially lead to human-to-human transmission, but also raise questions about the role of such transmissions in development of pre-existing immunity to other coronaviruses, such as SARS-CoV-2.

scholarly journals Host-cell recognition through GRP78 is enhanced in the new UK variant of SARS-CoV-2, in silico 

2021 ◽  
Author(s):  
Abdo A Elfiky ◽  
Ibrahim M Ibrahim
Keyword(s):  
Host Cell ◽  
Cell Receptor ◽  
Spike Protein ◽  
Cell Recognition ◽  
Receptor Binding Domain ◽  
Host Cell Receptor ◽  
Mutant Variant ◽  
New Variant ◽  
The Uk ◽  
Host Cell Recognition

Abstract New SARS-CoV-2 variant VUI 202012/01 started in the UK and currently spreading in Europe and Australia during the last few days. The new variant bears about nine mutations in the spike protein (Δ69-70, Δ145, N501Y, A570D, D614G, P681H, T716I, S982A, and D1118H). The N501Y lies in the receptor-binding domain (RBD) of the spike and interacts with the host-cell receptor ACE2 responsible for viral recognition and entry. We tried to simulate the system of ACE2-SARS-CoV-2 spike RBD in the wildtype and mutated isoform of the RBD (N501Y). Additionally, the GRP78 association with the ACE2-SARS-CoV-2 spike RBD is modeled at the presence of this mutant variant of the viral spike.

scholarly journals Catechin and Curcumin interact with corona (2019-nCoV/SARS-CoV2) viral S protein and ACE2 of human cell membrane: insights from Computational study and implication for intervention

2020 ◽  
Author(s):  
Atala B. Jena ◽  
Namrata Kanungo ◽  
Vinayak Nayak ◽  
G.B.N. Chainy ◽  
Jagneshwar Dandapat
Keyword(s):  
Binding Energy ◽  
Preventive Intervention ◽  
Computational Study ◽  
Protein S ◽  
Cell Receptor ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Host Cell Receptor ◽  
Recent Outbreak ◽  
First Time

Abstract The recent outbreak of the coronavirus (2019n-CoV) is an unprecedented threat for human health throughout the globe. In this regards development of a suitable intervention is the need of the hour. The viral spike protein (S-Protein) and the cognate host cell receptor ACE2 can prove to be effective. Here, through computational approaches we have reported two polyphenols, Catechin and Curcumin which have dual binding affinity i.e both the molecule binds to viral S-protein and as well as ACE2. Catechin binds with S-protein and ACE2 with binding energy of -10.5 Kcal/mol and -8.9 Kcal/mol, respectively. Catechin binds with a greater affinty than that of curcumin which has a binding energy of -7.9Kcal/mol and - 7.8Kcal/mol for S-protein and ACE2, respectively. While curcumin gets bound directly to receptor binding domain (RBD) of viral S-protein, catechin binds to near proximity of RBD sequence of S-protein. Molecular simulation study demonstrates that curcumin directly binds with RBD site of S-protein during 40-100ns. In contrast, catechin binds with S-protein near the RBD site and causes fluctuation in the amino acids present in the RBD and it’s near proximity. In conclusion, this computational study for the first time predicts the possibility of above two polyphenols, for therapeutic/preventive intervention.

scholarly journals Computational insights into differential interaction of mamalian ACE2 with the SARS-CoV-2 spike receptor binding domain

2021 ◽  
Author(s):  
Cecylia S. Lupala ◽  
Vikash Kumar ◽  
Xiao-dong Su ◽  
Chun Wu ◽  
Haiguang Liu
Keyword(s):  
Receptor Binding ◽  
Cell Receptor ◽  
Binding Domain ◽  
Cell Entry ◽  
Receptor Binding Domain ◽  
Sequence Structure ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Cell Receptor ◽  
Comparison Results ◽  
Horseshoe Bat

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causing agent of the COVID-19 pandemic, has spread globally. Angiotensin-converting enzyme 2 (ACE2) has been identified as the host cell receptor that binds to receptor-binding domain (RBD) of the SARS-COV-2 spike protein and mediates cell entry. Because the ACE2 proteins are widely available in mammals, it is important to investigate the interactions between the RBD and the ACE2 of other mammals. Here we analyzed the sequences of ACE2 proteins from 16 mammals and predicted the structures of ACE2-RBD complexes. Analyses on sequence, structure, and dynamics synergistically provide valuable insights into the interactions between ACE2 and RBD. The comparison results suggest that the ACE2 of bovine, cat and panda form strong binding with RBD, while in the cases of rat, least horseshoe bat, horse, pig, mouse and civet, the ACE2 proteins interact weakly with RBD.

scholarly journals Phylogenetic analysis of the betacoronavirus S1 subunit

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1389
Author(s):  
Irina Zyrianova
Keyword(s):  
Phylogenetic Analysis ◽  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Evolutionary History ◽  
Protein Sequences ◽  
Cell Receptor ◽  
Receptor Binding Domain ◽  
Host Cell Receptor ◽  
History Of ◽  
The Many

The ongoing pandemic outbreak of coronavirus disease 2019 (COVID-19) has been caused by the new betacoronavirus (BetaCoV) severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Together with other epidemic outbreaks of BetaCoV infectious diseases (Severe Acute Respiratory Syndrome (SARS) in 2002-2003 in China and Middle East Respiratory Syndrome (MERS) in 2012 in the Middle East, which have been caused by SARS-CoV and MERS-CoV, respectively), these events have generated interest in the coronaviruses (CoVs). Although many phylogenetic analyzes have been reported at a gene or protein level, there is no study as yet encompassing the many sequences publicly available for BetaCoVs, including those that have been manipulated in the lab. In this study, the phylogenetic analysis of 679 different S1 protein sequences of BetaCoVs from a total of 1595, which are publicly available in GenBank from the beginning of the pandemic event to April 2020, has been carried out. The S1 subunit is one part of the S (spike) protein, one of three CoV envelope proteins. The S1 subunit contains a host cell receptor binding domain. This domain is essential in the initiation of the infectious process. Therefore, its phylogenetic analysis is very important for studying CoV evolution. The phylogenetic analysis of BetaCoV S1 protein presented herein shows the evolutionary history of BetaCoVs from bovine CoV to SARS-CoV-2.

Progress in Studies on Structural and Remedial Aspects of Newly Born Coronavirus, SARS-CoV-2

2020 ◽  
Vol 20 (26) ◽  
pp. 2362-2378
Author(s):  
Satya P. Gupta
Keyword(s):  
Vaccine Development ◽  
Cell Receptor ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
N Protein ◽  
Host Cell Receptor ◽  
The Status ◽  
Novel Coronavirus

The article highlights an up-to-date progress in studies on structural and the remedial aspects of novel coronavirus 2019-nCoV, renamed as SARS-CoV-2, leading to the disease COVID-19, a pandemic. In general, all CoVs including SARS-CoV-2 are spherical positive single-stranded RNA viruses containing spike (S) protein, envelope (E) protein, nucleocapsid (N) protein, and membrane (M) protein, where S protein has a Receptor-binding Domain (RBD) that mediates the binding to host cell receptor, Angiotensin Converting Enzyme 2 (ACE2). The article details the repurposing of some drugs to be tried for COVID-19 and presents the status of vaccine development so far. Besides drugs and vaccines, the role of Convalescent Plasma (CP) therapy to treat COVID-19 is also discussed.

scholarly journals Monoclonal antibodies for the S2 subunit of spike of SARS-CoV cross-react with the newly-emerged SARS-CoV-2

2020 ◽  
Author(s):  
Zhiqiang Zheng ◽  
Vanessa M. Monteil ◽  
Sebastian Maurer-Stroh ◽  
Chow Wenn Yew ◽  
Carol Leong ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cell Receptor ◽  
Cross Reactivity ◽  
Diagnostic Assays ◽  
Host Cell Receptor ◽  
High Sequence Conservation ◽  
Infected Cells ◽  
Novel Coronavirus ◽  
Multiple Strains ◽  
Human Infections

AbstractThe emergence of a novel coronavirus, SARS-CoV-2, at the end of 2019 has resulted in widespread human infections across the globe. While genetically distinct from SARS-CoV, the etiological agent that caused an outbreak of severe acute respiratory syndrome (SARS) in 2003, both coronaviruses exhibit receptor binding domain (RBD) conservation and utilize the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), for virus entry. Therefore, it will be important to test the cross-reactivity of antibodies that have been previously generated against the surface spike (S) glycoprotein of SARS-CoV in order to aid research on the newly emerged SARS-CoV-2. Here, we show that an immunogenic domain in the S2 subunit of SARS-CoV S is highly conserved in multiple strains of SARS-CoV-2. Consistently, four murine monoclonal antibodies (mAbs) raised against this immunogenic SARS-CoV fragment were able to recognise the S protein of SARS-CoV-2 expressed in a mammalian cell line. Importantly, one of them (mAb 1A9) was demonstrated to detect S in SARS-CoV-2-infected cells. To our knowledge, this is the first study showing that mAbs targeting the S2 domain of SARS-CoV can cross-react with SARS-CoV-2 and this observation is consistent with the high sequence conservation in the S2 subunit. These cross-reactive mAbs may serve as tools useful for SARS-CoV-2 research as well as for the development of diagnostic assays for its associated coronavirus disease COVID-19.

scholarly journals New Method To Generate Enzymatically DeficientClostridium difficile Toxin B as an Antigen for Immunization

2000 ◽  
Vol 68 (3) ◽  
pp. 1094-1101 ◽  
Author(s):  
Harald Genth ◽  
Jörg Selzer ◽  
Christian Busch ◽  
Jürgen Dumbach ◽  
Fred Hofmann ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Receptor Binding ◽  
Rho Gtpases ◽  
Catalytic Domain ◽  
Cell Receptor ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Intact Cells ◽  
Toxin B ◽  
The Family

ABSTRACT The family of the large clostridial cytotoxins, encompassingClostridium difficile toxins A and B as well as the lethal and hemorrhagic toxins from Clostridium sordellii, monoglucosylate the Rho GTPases by transferring a glucose moiety from the cosubstrate UDP-glucose. Here we present a new detoxification procedure to block the enzyme activity by treatment with the reactive UDP-2′,3′-dialdehyde to result in alkylation of toxin A and B. Alkylation is likely to occur in the catalytic domain, because the native cosubstrate UDP-glucose completely protected the toxins from inactivation and the alkylated toxin competes with the native toxin at the cell receptor. Alkylated toxins are good antigens resulting in antibodies recognizing only the C-terminally located receptor binding domain, whereas formaldehyde treatment resulted in antibodies recognizing both the receptor binding domain and the catalytic domain, indicating that the catalytic domain is concealed under native conditions. Antibodies against the native catalytic domain (amino acids 1 through 546) and those holotoxin antibodies recognizing the catalytic domain inhibited enzyme activity. However, only antibodies against the receptor binding domain protected intact cells from the cytotoxic activity of toxin B, whereas antibodies against the catalytic domain were protective only when inside the cell.

scholarly journals Genomic and Proteomic Comparative Analysis of SARS-CoV-2 versus SARS-CoV-GD01

2020 ◽  
Author(s):  
Abdallah A. Hassanin ◽  
EL-Sayed I. Mahgoub ◽  
Basel Sitohy ◽  
Mahmoud Sitohy
Keyword(s):  
Bioinformatics Analysis ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Cell Receptor ◽  
Gene Encoding ◽  
Spike Gene ◽  
Insertion And Deletion ◽  
Host Cell Receptor ◽  
Genes Encoding ◽  
Pathogenic Action

Abstract Background Since the emergence of the pandemic novel pneumonia (COVID-19) disease in Wuhan city in China in November 2019, it is becoming holistically urgent to discover and definitely determine the potential origin of causative virus of this disease, SARS-CoV2 to understand its pathogenic action an better design proper remedies. Methods Using bioinformatics analysis, the whole genome of SARS-CoV2 emerging in 2020 and its deduced proteome were compared with the corresponding information on SARS-CoV-GD01 having emerged in 2003 in China. The genomes squences of the two viruses were obtained from NCBI. Alignment of protein sequences for all genes of both genomes were performed and displayed using Clustal Omega data base. Results Bioinformatics analysis revealed 10 genes encoding 10 proteins in the SARS-CoV2 genome instead of 11 genes encoding 12 proteins in the case of SARS-CoV-GD01, where the first gene is uniquely encoding two glycoproteins. Additionally, bio-informatics analysis disclosed variations in SARS-CoV2 genome size as a result of nucleotides insertion and deletion in all genes of the virus especially orf1ab gene, spike gene, and ORF10 gene. The most conspicuous alteration is apparently noticed in the spike gene, encoding for a novel protein enabling the virus to attach to the cell membrane via the interaction with host cell receptor, initiating probably a new pathway of infection and a specific pathogenic action. This alteration is Conclusions The big alterations in the genome of SARS-CoV-2 from that of SARS-CoV-GD01 may be potentially responsible for the worldwide witnessed high virulence and accelerated spread. The qualified and quantified information presented in the current study on the SARS-CoV-2, detailing the specificity and the magnitude of genomic and proteomic alterations from SARS-CoV-GD01, developed probably during 16 years will not only enable designing right drugs and strategies of confronting the current viral version, but it may rather allow to extrapolate and foresee potential outbreaks of newer versions during the coming decades. At the time of epidemics, nonspecific ways and drugs should be resorted to for confronting emergent viral infections. Chemically modified positively charged proteins and peptides can offer a wealth of potential antiviral agents but need more clinical research.

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