Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 58
Filter
1.
Asia-Pacific Journal of Molecular Biology and Biotechnology ; 29:57, 2021.
Article in English | ProQuest Central | ID: covidwho-1812906

ABSTRACT

The novel human coronavirus (CoV) 2019 known as COVID-19, similar to previous CoVs infections outbreaks has posed a serious and an unprecedented challenge on the entire health care system in the world, that needs aggressive preventive and easily accessible measures, policies for effective regular disinfection. Rampant use of disinfectants may pose toxicity to human, environmental hazards and, in some cases, decrease effectiveness and development of resistance due to other ingredients in the disinfectant agents. This review comprehensively highlights the effects of physical and chemical countermeasures and their related potential toxicity on human and environment. The study reveals that physical inactivation especially the effects of temperature, humidity and light mostly ultraviolet-C (UV-C), have significantly demonstrated proven efficacy in reducing the spread of CoV infections. Similarly, chemical countermeasures especially alcoholand iodine-based disinfecting agents have shown potentials inhibition against the survival of the viruses and other pathogenic micro-organisms on surfaces. Large number of disinfectants were reported to contain corrosive chemicals that are toxic to humans especially children and destroy the environment due to unhealthy accumulation and pollution, and other additional ingredients having potentials to develop resistance and decrease effectiveness of the disinfectants. This review sumarizes the imporatnce of physical and chemical preventive countermeasures currently in use against CoV infections for further modifications and translational study to design improved disinfecting agents.

2.
Front Cell Dev Biol ; 10:849298, 2022.
Article in English | PubMed | ID: covidwho-1809352

ABSTRACT

Recent studies on the epitranscriptomic code of SARS-CoV-2 infection have discovered various RNA modifications, such as N6-methyladenosine (m6A), pseudouridine (Ψ), and 2'-O-methylation (Nm). The effects of RNA methylation on SARS-CoV-2 replication and the enzymes involved in this mechanism are emerging. In this review, we summarize the advances in this emerging field and discuss the role of various players such as readers, writers, and erasers in m6A RNA methylation, the role of pseudouridine synthase one and seven in epitranscriptomic modification Ψ, an isomer of uridine, and role of nsp16/nsp10 heterodimer in 2'-O-methylation of the ribose sugar of the first nucleotide of SARS-CoV-2 mRNA. We also discuss RNA expression levels of various enzymes involved in RNA modifications in blood cells of SARS-CoV-2 infected individuals and their impact on host mRNA modification. In conclusion, these observations will facilitate the development of novel strategies and therapeutics for targeting RNA modification of SARS-CoV-2 RNA to control SARS-CoV-2 infection.

3.
Biochem J ; 479(6): 731-750, 2022 03 31.
Article in English | MEDLINE | ID: covidwho-1764226

ABSTRACT

The interplay between innate immunity and coagulation after infection or injury, termed immunothrombosis, is the primary cause of disseminated intravascular coagulation (DIC), a condition that occurs in sepsis. Thrombosis associated with DIC is the leading cause of death worldwide. Interest in immunothrombosis has grown because of COVID-19, the respiratory disease caused by SARS-CoV-2, which has been termed a syndrome of dysregulated immunothrombosis. As the relatively new field of immunothrombosis expands at a rapid pace, the focus of academic and pharmacological research has shifted from generating treatments targeted at the traditional 'waterfall' model of coagulation to therapies better directed towards immune components that drive coagulopathies. Immunothrombosis can be initiated in macrophages by cleavage of the non-canonical inflammasome which contains caspase-11. This leads to release of tissue factor (TF), a membrane glycoprotein receptor that forms a high-affinity complex with coagulation factor VII/VIIa to proteolytically activate factors IX to IXa and X to Xa, generating thrombin and leading to fibrin formation and platelet activation. The mechanism involves the post-translational activation of TF, termed decryption, and release of decrypted TF via caspase-11-mediated pyroptosis. During aberrant immunothrombosis, decryption of TF leads to thromboinflammation, sepsis, and DIC. Therefore, developing therapies to target pyroptosis have emerged as an attractive concept to counteract dysregulated immunothrombosis. In this review, we detail the three mechanisms of TF control: concurrent induction of TF, caspase-11, and NLRP3 (signal 1); TF decryption, which increases its procoagulant activity (signal 2); and accelerated release of TF into the intravascular space via pyroptosis (signal 3). In this way, decryption of TF is analogous to the two signals of NLRP3 inflammasome activation, whereby induction of pro-IL-1ß and NLRP3 (signal 1) is followed by activation of NLRP3 (signal 2). We describe in detail TF decryption, which involves pathogen-induced alterations in the composition of the plasma membrane and modification of key cysteines on TF, particularly at the location of the critical, allosterically regulated disulfide bond of TF in its 219-residue extracellular domain. In addition, we speculate towards the importance of identifying new therapeutics to block immunothrombotic triggering of TF, which can involve inhibition of pyroptosis to limit TF release, or the direct targeting of TF decryption using cysteine-modifying therapeutics.


Subject(s)
COVID-19 , Thrombosis , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , COVID-19/drug therapy , Humans , Inflammation/complications , Pyroptosis , SARS-CoV-2 , Thromboplastin/metabolism
4.
Chemosensors ; 10(3):103, 2022.
Article in English | ProQuest Central | ID: covidwho-1760411

ABSTRACT

Printing technology promises a viable solution for the low-cost, rapid, flexible, and mass fabrication of biosensors. Among the vast number of printing techniques, screen printing and inkjet printing have been widely adopted for the fabrication of biosensors. Screen printing provides ease of operation and rapid processing;however, it is bound by the effects of viscous inks, high material waste, and the requirement for masks, to name a few. Inkjet printing, on the other hand, is well suited for mass fabrication that takes advantage of computer-aided design software for pattern modifications. Furthermore, being drop-on-demand, it prevents precious material waste and offers high-resolution patterning. To exploit the features of inkjet printing technology, scientists have been keen to use it for the development of biosensors since 1988. A vast number of fully and partially inkjet-printed biosensors have been developed ever since. This study presents a short introduction on the printing technology used for biosensor fabrication in general, and a brief review of the recent reports related to virus, enzymatic, and non-enzymatic biosensor fabrication, via inkjet printing technology in particular.

5.
Postgrad Med ; : 1-10, 2022 Mar 30.
Article in English | MEDLINE | ID: covidwho-1740549

ABSTRACT

We must recognize the limitations of the current situation and vaccines where SARS-CoV-2 variants continue to transform and spread and need to build strategies to maintain and promote health in adherence to the suggested recommended action of the WHO. The purpose of this review is to examine the literature and latest research on the effects of physical activity (PA) on health in preparation for the SARS-CoV-2 strain and future infectious diseases era. In addition, it provides some general guidelines for actionable PA. We performed a literature search using Scopus, Riss, MEDLINE, and Google Scholar, this review method was a narrative literature review of the available literature and latest literature regarding health and PA-related factors during the COVID-19 pandemic. As a result, PA suggests opportunities to not only maintain and promote health by strengthening the immune system in an era where the COVID-19 variant is a crisis but also implement opportunities for well-being (WB), healthy lifestyles, and long-term health improvement. In particular, maintaining a regular PA routine outdoors or at home could be an important means to lower infection rates and maintain health during the potential impact of the current COVID-19 crisis and future pandemics (i.e. dramatic moments). The clinical relevance of the present review is crucial to understanding the impact of PA on WB, lifestyle, physical and mental health, maintaining regular PA, and important preventive factor to better prepare for the era of COVID-19 variants and similar pandemics in the future as it is emphasized as a prevention strategy and key strategy for continuous health promotion.

6.
Viruses ; 14(3)2022 03 04.
Article in English | MEDLINE | ID: covidwho-1732238

ABSTRACT

The spike proteins of enveloped viruses are transmembrane glycoproteins that typically undergo post-translational attachment of palmitate on cysteine residues on the cytoplasmic facing tail of the protein. The role of spike protein palmitoylation in virus biogenesis and infectivity is being actively studied as a potential target of novel antivirals. Here, we report that palmitoylation of the first five cysteine residues of the C-terminal cysteine-rich domain of the SARS-CoV-2 S protein are indispensable for infection, and palmitoylation-deficient spike mutants are defective in membrane fusion. The DHHC9 palmitoyltransferase interacts with and palmitoylates the spike protein in the ER and Golgi and knockdown of DHHC9 results in reduced fusion and infection of SARS-CoV-2. Two bis-piperazine backbone-based DHHC9 inhibitors inhibit SARS-CoV-2 S protein palmitoylation and the resulting progeny virion particles released are defective in fusion and infection. This establishes these palmitoyltransferase inhibitors as potential new intervention strategies against SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Lipoylation , Spike Glycoprotein, Coronavirus
7.
25th International Computer Science and Engineering Conference, ICSEC 2021 ; : 454-458, 2021.
Article in English | Scopus | ID: covidwho-1722922

ABSTRACT

Globally, the COVID-19 pandemic has caused dev-Astation and continues to do so even a year after its first outbreak. Behavioral modifications could help to mitigate a mechanism for acquiring and spreading illnesses. Using wearable devices such as smartwatches to recognize face contact has the opportunity to decrease face touching and, therefore, the spread of respiratory disease through fomite transmission. The purpose of this paper is to demonstrate how we can utilize accelerometer data from wristwatch sensors to identify face touching actions using deep learning techniques. We proposed the BiGRU deep learning model for the high-performance recognition of hand-To-face actions. The Face Touching dataset is used as a benchmark for evaluating the recognition accuracy of deep learning networks, including our network model. The experimental findings indicate that the BiGRU surpasses other baseline deep learning models regarding accuracy (98.56%) and F1-score (98.56%). © 2021 IEEE.

8.
Elife ; 112022 01 21.
Article in English | MEDLINE | ID: covidwho-1716085

ABSTRACT

Methyltransferase like-3 (METTL3) and METTL14 complex transfers a methyl group from S-adenosyl-L-methionine to N6 amino group of adenosine bases in RNA (m6A) and DNA (m6dA). Emerging evidence highlights a role of METTL3-METTL14 in the chromatin context, especially in processes where DNA and RNA are held in close proximity. However, a mechanistic framework about specificity for substrate RNA/DNA and their interrelationship remain unclear. By systematically studying methylation activity and binding affinity to a number of DNA and RNA oligos with different propensities to form inter- or intra-molecular duplexes or single-stranded molecules in vitro, we uncover an inverse relationship for substrate binding and methylation and show that METTL3-METTL14 preferentially catalyzes the formation of m6dA in single-stranded DNA (ssDNA), despite weaker binding affinity to DNA. In contrast, it binds structured RNAs with high affinity, but methylates the target adenosine in RNA (m6A) much less efficiently than it does in ssDNA. We also show that METTL3-METTL14-mediated methylation of DNA is largely restricted by structured RNA elements prevalent in long noncoding and other cellular RNAs.


Subject(s)
DNA Methylation/physiology , Methyltransferases/metabolism , DNA, Single-Stranded/metabolism , Deoxyadenosines/metabolism , Humans , RNA/chemistry , RNA/metabolism
9.
Front Cell Dev Biol ; 10: 807149, 2022.
Article in English | MEDLINE | ID: covidwho-1714988

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious virus of the coronavirus family that causes coronavirus disease-19 (COVID-19) in humans and a number of animal species. COVID-19 has rapidly propagated in the world in the past 2 years, causing a global pandemic. Here, we performed proteomic analysis of plasma samples from COVID-19 patients compared to healthy control donors in an exploratory study to gain insights into protein-level changes in the patients caused by SARS-CoV-2 infection and to identify potential proteomic and posttranslational signatures of this disease. Our results suggest a global change in protein processing and regulation that occurs in response to SARS-CoV-2, and the existence of a posttranslational COVID-19 signature that includes an elevation in threonine phosphorylation, a change in glycosylation, and a decrease in arginylation, an emerging posttranslational modification not previously implicated in infectious disease. This study provides a resource for COVID-19 researchers and, longer term, and will inform our understanding of this disease and its treatment.

10.
Curr Med Chem ; 2022 Feb 16.
Article in English | MEDLINE | ID: covidwho-1690553

ABSTRACT

BACKGROUND: The current coronavirus disease 2019 (COVID-19) pandemic, since first reported in Wuhan, has inspired worldwide efforts to develop effective COVID-19 vaccination strategies. mRNA vaccines encoding COVID-19 antigens gain lead in this global race due to their high effectiveness and simple manufacturing process. Notably, two COVID-19 mRNA vaccines, mRNA-1273 and BNT162b2, have survived in clinical trials and been authorized for emergency use across a range of countries. SUMMARY: Recent advances on mRNA vaccine development for COVID-19 are discussed in this perspective, including sequence design, chemical modification, manufacturing process and in vivo delivery. Phase I to IV clinical trials of mRNA-1273 and BNT162b2 are then summarized, respectively. PERSPECTIVE: Using mRNA vaccines serves as a promising strategy to achieve mass vaccination in the COVID-19 pandemic. We hope that future studies of mRNA vaccine technology would overcome existing limitations and help people cope with COVID-19.

11.
Epigenomics ; 14(3): 153-162, 2022 02.
Article in English | MEDLINE | ID: covidwho-1622527

ABSTRACT

Smoking could predispose individuals to a more severe COVID-19 by upregulating a particular gene known as mdig, which is mediated through a number of well-known histone modifications. Smoking might regulate the transcription-activating H3K4me3 mark, along with the transcription-repressing H3K9me3 and H3K27me3 marks, in a way to favor SARS-CoV-2 entry by enhancing the expression of ACE2, NRP1 and NRP2, AT1R, CTSD and CTSL, PGE2 receptors 2-4, SLC6A20 and IL-6, all of which interact either directly or indirectly with important receptors, facilitating viral entry in COVID-19.


Lay abstract The role of smoking in development of several respiratory diseases has been clearly established. A significant proportion of these deleterious effects is mediated through epigenetic mechanisms, particularly histone modifications. Recent evidence indicates that smoking induces the expression of a mediator known as mdig, which in turn alters the transcription of several key proteins that have been implicated in development of COVID-19.


Subject(s)
COVID-19/genetics , Dioxygenases/genetics , Epigenesis, Genetic , Histone Demethylases/genetics , Histones/genetics , Nuclear Proteins/genetics , Protein Processing, Post-Translational , Smoking/genetics , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/diagnosis , COVID-19/metabolism , COVID-19/virology , Cathepsin D/genetics , Cathepsin D/metabolism , Cathepsin L/genetics , Cathepsin L/metabolism , Dioxygenases/metabolism , Histone Demethylases/metabolism , Histones/metabolism , Humans , Interleukin-6/genetics , Interleukin-6/metabolism , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Methylation , Neuropilin-1/genetics , Neuropilin-1/metabolism , Neuropilin-2/genetics , Neuropilin-2/metabolism , Nuclear Proteins/metabolism , Protein Isoforms/genetics , Protein Isoforms/metabolism , Receptor, Angiotensin, Type 1/genetics , Receptor, Angiotensin, Type 1/metabolism , Receptors, Prostaglandin E/genetics , Receptors, Prostaglandin E/metabolism , Risk Factors , SARS-CoV-2/genetics , SARS-CoV-2/growth & development , SARS-CoV-2/metabolism , Smoking/metabolism , Smoking/pathology , Virus Internalization
12.
Int J Environ Res Public Health ; 18(24)2021 12 09.
Article in English | MEDLINE | ID: covidwho-1572444

ABSTRACT

Early in the SARS-CoV-2 pandemic, many national public health authorities implemented non-pharmaceutical interventions to mitigate disease outbreaks. Panamá established mandatory mask use two months after its first documented case. Initial compliance was high, but diverse masks were used in public areas. We studied behavioral dynamics of mask use through the first two COVID-19 waves in Panama, to improve the implementation of effective, low-cost public health containment measures when populations are exposed to novel air-borne pathogens. Mask use behavior was recorded from pedestrians in four Panamanian populations (August to December 2020). We recorded facial coverings and if used, the type of mask, and gender and estimated age of the wearer. Our results showed that people were highly compliant (>95%) with mask mandates and demonstrated important population-level behaviors: (1) decreasing use of cloth masks over time, and increasing use of surgical masks; (2) mask use was 3-fold lower in suburban neighborhoods than other public areas and (3) young people were least likely to wear masks. Results help focus on highly effective, low-cost, public health interventions for managing and controlling a pandemic. Considerations of behavioral preferences for different masks, relative to pricing and availability, are essential for optimizing public health policies. Policies to increase the availability of effective masks, and behavioral nudges to increase acceptance, and to facilitate mask usage, during the ongoing SARS-CoV-2 pandemic, and for future pandemics of respiratory pathogens, are key tools, especially for nations lagging in access to expensive vaccines and pharmacological approaches.


Subject(s)
COVID-19 , SARS-CoV-2 , Adolescent , Humans , Masks , Pandemics , Public Health
13.
Curr Diabetes Rev ; 2021 Dec 07.
Article in English | MEDLINE | ID: covidwho-1560669

ABSTRACT

OBJECTIVE: The objective of this study is to evaluate the impact of the COVID-19 lockdown on glycemic control and accompanying laboratory parameters in patients with type 2 Diabetes Mellitus. RESEARCH DESIGN AND METHODS: This study is a retrospective cohort study that was done on a multicenter level. It was conducted during the lockdown in 341 individuals. HbA1c was tested to measure glycemic control immediately before and after the lockdown period that lasted for 13 weeks. RESULTS: The primary outcome was the improvement of mean HbA1C after 13 weeks of lockdown compared to the pre-lockdown HbA1C. It was found that the mean HbA1C improved from 7.5±1.5 to 7.3±1.5 with a p-value of 0.001. CONCLUSION: Our study showed that patients with type 2 diabetes mellitus exhibited an improvement in their glycemic control after the period of lockdown.

14.
Int J Environ Res Public Health ; 18(22)2021 11 09.
Article in English | MEDLINE | ID: covidwho-1534036

ABSTRACT

INTRODUCTION: Modifications to electronic nicoti ne delivery systems (ENDS) can pose health risks to users. This study explored users' motivations for modifying ENDS devices and how perceived risks of modifications influenced modification behaviors as product availability and device characteristics changed over time. METHOD: We conducted nine focus groups (February-June 2020) with 32 current ENDS users (18+, used ENDS in the past 30 days, and had been using ENDS for more than 2 months). RESULTS: Participants primarily modified ENDS devices to improve their experiences, such as experimenting with flavor, controlling nicotine levels, or using cannabis products with ENDS. Another reason for modifying was routine maintenance to ensure a satisfactory experience, including maintaining coils and keeping batteries charged. The broader availability of ENDS products shifted modification behaviors over time, with newer devices making some modifications (e.g., coil replacement) easier and making more intricate modifications (e.g., building coil from scratch) less common. Participants were aware of modification dangers and cited perceived risk as the reason for avoiding certain modifications, such as battery alterations. CONCLUSIONS: Modifications of ENDS are ongoing and evolving among users and should be considered by the Food and Drug Administration (FDA) and other regulatory decision-makers as product authorization reviews are conducted and product standards are developed.


Subject(s)
Electronic Nicotine Delivery Systems , Vaping , Flavoring Agents , Focus Groups , Humans , Motivation , Nicotine
15.
Front Neurol ; 12: 744796, 2021.
Article in English | MEDLINE | ID: covidwho-1497107

ABSTRACT

Introduction: The coronavirus disease 2019 (COVID-19) pandemic represents a unified lifestyle modification model, which was developed by the globally applied measures. The lockdowns designed the perfect study settings for observing the interaction between migraine and the adopted changes in lifestyle. An experiment in vivo took place unexpectedly to determine how the lockdown lifestyle modifications can influence migraine. Subsection 1: Overall lifestyle modifications during the pandemic: People stay home, and outdoor activities and public contacts are restricted. Sleep is disturbed. Media exposure and prolonged screen use are increased. Working conditions change. In-person consultations and therapies are canceled. The beneficial effects of short-term stress, together with the harmful effects of chronic stress, were observed during the pandemic. Subsection 2: Short-term effects: Substantial lifestyle changes happened, and knowing how vulnerable migraine patients are, one could hypothesize that this would have resulted in severe worsening of headache. Surprisingly, even though the impacts of changing social conditions were significant, some patients (including children) experienced a reduction in their migraine during the first lockdown. Subsection 3: Long-term effects: Unfortunately, headache frequency returned to the basal state during the second pandemic wave. The risk factors that could have led to this worsening are the long-term disruption of sleep and dietary habits, stress, anxiety, depression, non-compliance to treatment, and working during the pandemic. Discussion: Sudden short-term lifestyle changes taking migraine patients out of their usual routine may be beneficial for headache management. It is not necessary to have a natural disaster in place for a drastic lifestyle modification with 6-8-week duration, if we know that this will improve migraine.

16.
Nano Today ; 40: 101267, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1450199

ABSTRACT

Nanoparticles provide new opportunities in merging therapeutics and new materials, with current research efforts just beginning to scratch the surface of their diverse benefits and potential applications. One such application, the use of inorganic nanoparticles in antiseptic coatings to prevent pathogen transmission and infection, has seen promising developments. Notably, the high reactive surface area to volume ratio and unique chemical properties of metal-based nanoparticles enables their potent inactivation of viruses. Nanoparticles exert their virucidal action through mechanisms including inhibition of virus-cell receptor binding, reactive oxygen species oxidation and destructive displacement bonding with key viral structures. The prevention of viral outbreaks is one of the foremost challenges to medical science today, emphasizing the importance of research efforts to develop nanoparticles for preventative antiviral applications. In this review, the use of nanoparticles to inactivate other viruses, such as influenza, HIV-1, or norovirus, among others, will be discussed to extrapolate broad-spectrum antiviral mechanisms that could also inhibit SARS-CoV-2 pathogenesis. This review analyzes the published literature to highlight the current state of knowledge regarding the efficacy of metal-based nanoparticles and other antiviral materials for biomedical, sterile polymer, and surface coating applications.

17.
Biomedicines ; 9(10)2021 Sep 30.
Article in English | MEDLINE | ID: covidwho-1444098

ABSTRACT

The protein kinase CK2 (CK2) family encompasses a small number of acidophilic serine/threonine kinases that phosphorylate substrates involved in numerous biological processes including apoptosis, cell proliferation, and the DNA damage response. CK2 has also been implicated in many human malignancies and other disorders including Alzheimer's and Parkinson's diseases, and COVID-19. Interestingly, no single mechanism describes how CK2 is regulated, including activation by external proteins or domains, phosphorylation, or dimerization. Furthermore, the kinase has an elongated activation loop that locks the kinase into an active conformation, leading CK2 to be labelled a constitutively active kinase. This presents an interesting paradox that remains unanswered: how can a constitutively active kinase regulate biological processes that require careful control? Here, we highlight a selection of studies where CK2 activity is regulated at the substrate level, and discuss them based on the regulatory mechanism. Overall, this review describes numerous biological processes where CK2 activity is regulated, highlighting how a constitutively active kinase can still control numerous cellular activities. It is also evident that more research is required to fully elucidate the mechanisms that regulate CK2 and what causes aberrant CK2 signaling in disease.

18.
Glycobiology ; 31(9): 1080-1092, 2021 09 20.
Article in English | MEDLINE | ID: covidwho-1434394

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), started in 2019 in China and quickly spread into a global pandemic. Nucleocapsid protein (N protein) is highly conserved and is the most abundant protein in coronaviruses and is thus a potential target for both vaccine and point-of-care diagnostics. N Protein has been suggested in the literature as having posttranslational modifications (PTMs), and accurately defining these PTMs is critical for its potential use in medicine. Reports of phosphorylation of N protein have failed to provide detailed site-specific information. We have performed comprehensive glycomics, glycoproteomics and proteomics experiments on two different N protein preparations. Both were expressed in HEK293 cells; one was in-house expressed and purified without a signal peptide (SP) sequence, and the other was commercially produced with a SP channeling it through the secretory pathway. Our results show completely different PTMs on the two N protein preparations. The commercial product contained extensive N- and O-linked glycosylation as well as O-phosphorylation on site Thr393. Conversely, the native N Protein model had O-phosphorylation at Ser176 and no glycosylation, highlighting the importance of knowing the provenance of any commercial protein to be used for scientific or clinical studies. Recent studies have indicated that N protein can serve as an important diagnostic marker for COVID-19 and as a major immunogen by priming protective immune responses. Thus, detailed structural characterization of N protein may provide useful insights for understanding the roles of PTMs on viral pathogenesis, vaccine design and development of point-of-care diagnostics.


Subject(s)
Coronavirus Nucleocapsid Proteins/metabolism , Protein Processing, Post-Translational/physiology , SARS-CoV-2/metabolism , Amino Acid Motifs , Amino Acid Sequence , Binding Sites , Coronavirus Nucleocapsid Proteins/chemistry , Glycosylation , HEK293 Cells , Humans , Phosphorylation , SARS-CoV-2/chemistry
19.
Chembiochem ; 22(22): 3199-3207, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1406083

ABSTRACT

Site-specific protein modifications are vital for biopharmaceutical drug development. Gluconoylation is a non-enzymatic, post-translational modification of N-terminal HisTags. We report high-yield, site-selective in vitro α-aminoacylation of peptides, glycoproteins, antibodies, and virus-like particles (VLPs) with azidogluconolactone at pH 7.5 in 1 h. Conjugates slowly hydrolyse, but diol-masking with borate esters inhibits reversibility. In an example, we multimerise azidogluconoylated SARS-CoV-2 receptor-binding domain (RBD) onto VLPs via click-chemistry, to give a COVID-19 vaccine. Compared to yeast antigen, HEK-derived RBD was immunologically superior, likely due to observed differences in glycosylation. We show the benefits of ordered over randomly oriented multimeric antigen display, by demonstrating single-shot seroconversion and best virus-neutralizing antibodies. Azidogluconoylation is simple, fast and robust chemistry, and should accelerate research and development.


Subject(s)
Azides/chemistry , COVID-19 Vaccines/chemistry , Gluconates/chemistry , Glycine/chemistry , Histidine/chemistry , Lactones/chemistry , Vaccines, Virus-Like Particle/chemistry , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/immunology , Azides/immunology , COVID-19 Vaccines/immunology , Gluconates/immunology , Glycine/immunology , Histidine/immunology , Humans , Lactones/immunology , Models, Molecular , Molecular Structure , Vaccines, Virus-Like Particle/immunology
20.
J Cell Commun Signal ; 15(4): 595-600, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1391998

ABSTRACT

Severe acute respiratory syndrome coronaviruses (SARS-CoVs) caused worldwide epidemics over the past few decades. Extensive studies on various strains of coronaviruses provided a basic understanding of the pathogenesis of the disease. Presently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading a global pandemic with unprecedented challenges. This is the third coronavirus outbreak of this century. A signaling pathway map of signaling events induced by SARS-CoV infection is not yet available. In this study, we present a literature-annotated signaling pathway map of reactions induced by SARS-CoV infected cells. Multiple signaling modules were found to be orchestrated including PI3K-AKT, Ras-MAPK, JAK-STAT, Type 1 IFN and NFκB. The signaling pathway map of SARS-CoV consists of 110 molecules and 101 reactions mediated by SARS-CoV proteins. The pathway reaction data are available in various community standard data exchange formats including Systems Biology Graphical Notation (SBGN). The pathway map is publicly available through the GitHub repository and data in various formats can be freely downloadable.

SELECTION OF CITATIONS
SEARCH DETAIL