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1.
Carbohydr Res ; 518: 108574, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1821162

ABSTRACT

Can envelope glycans be targeted to stop viral pandemics? Here we address this question by using molecular dynamics simulations to study the binding between 10 synthetic carbohydrate receptors (SCRs) and the 33 N-glycans most commonly found on the surfaces of enveloped viruses, including Zika virus and SARS-CoV-2. Based on association quotients derived from these simulations, we classified the SCRs as weak binders, promiscuous binders, or selective binders. The SCRs almost exclusively associate at the Man3GlcNAc2 core, which is common to all N-glycans, but the binding affinity between the SCR⋅glycan pair depends on the noncovalent interactions between the heterocycle rings and the glycan antennae. Systematic variations in the glycan and SCR structures reveal relationships that could guide the design of SCRs to attain affinity and selectivity towards a chosen envelope glycan target. With these results, envelope glycans, which are currently considered "undruggable", could become viable targets for new therapeutic strategies.


Subject(s)
COVID-19 , Receptors, Artificial , Zika Virus Infection , Zika Virus , Carbohydrates/chemistry , Humans , Molecular Dynamics Simulation , Polysaccharides/chemistry , Receptors, Artificial/chemistry , SARS-CoV-2 , Zika Virus/metabolism
2.
Virulence ; 13(1): 670-683, 2022 12.
Article in English | MEDLINE | ID: covidwho-1791073

ABSTRACT

Glycans are among the most important cell molecular components. However, given their structural diversity, their functions have not been fully explored. Glycosylation is a vital post-translational modification for various proteins. Many bacteria and viruses rely on N-linked and O-linked glycosylation to perform critical biological functions. The diverse functions of glycosylation on viral proteins during viral infections, including Dengue, Zika, influenza, and human immunodeficiency viruses as well as coronaviruses have been reported. N-linked glycosylation is the most common form of protein modification, and it modulates folding, transportation and receptor binding. Compared to N-linked glycosylation, the functions of O-linked viral protein glycosylation have not been comprehensively evaluated. In this review, we summarize findings on viral protein glycosylation, with particular attention to studies on N-linked glycosylation in viral life cycles. This review informs the development of virus-specific vaccines or inhibitors.


Subject(s)
Zika Virus Infection , Zika Virus , Glycosylation , Host Microbial Interactions , Humans , Protein Processing, Post-Translational , Viral Proteins/metabolism , Virulence , Zika Virus/metabolism
3.
FEBS Lett ; 595(23): 2854-2871, 2021 12.
Article in English | MEDLINE | ID: covidwho-1508599

ABSTRACT

SARS-CoV-2 has infected hundreds of millions of people with over four million dead, resulting in one of the worst global pandemics in recent history. Neurological symptoms associated with COVID-19 include anosmia, ageusia, headaches, confusion, delirium, and strokes. These may manifest due to viral entry into the central nervous system (CNS) through the blood-brain barrier (BBB) by means of ill-defined mechanisms. Here, we summarize the abilities of SARS-CoV-2 and other neurotropic RNA viruses, including Zika virus and Nipah virus, to cross the BBB into the CNS, highlighting the role of magnetic resonance imaging (MRI) in assessing presence and severity of brain structural changes in COVID-19 patients. We present new insight into key mutations in SARS-CoV-2 variants B.1.1.7 (P681H) and B.1.617.2 (P681R), which may impact on neuropilin 1 (NRP1) binding and CNS invasion. We postulate that SARS-CoV-2 may infect both peripheral cells capable of crossing the BBB and brain endothelial cells to traverse the BBB and spread into the brain. COVID-19 patients can be followed up with MRI modalities to better understand the long-term effects of COVID-19 on the brain.


Subject(s)
Blood-Brain Barrier , Henipavirus Infections , Nipah Virus , SARS-CoV-2 , Zika Virus Infection , Zika Virus , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/physiopathology , Blood-Brain Barrier/virology , COVID-19/epidemiology , COVID-19/genetics , COVID-19/metabolism , COVID-19/physiopathology , Henipavirus Infections/epidemiology , Henipavirus Infections/genetics , Henipavirus Infections/metabolism , Henipavirus Infections/physiopathology , Humans , Mutation , Nipah Virus/genetics , Nipah Virus/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Zika Virus/genetics , Zika Virus/metabolism , Zika Virus Infection/epidemiology , Zika Virus Infection/genetics , Zika Virus Infection/metabolism , Zika Virus Infection/physiopathology
4.
FEBS Lett ; 595(23): 2854-2871, 2021 12.
Article in English | MEDLINE | ID: covidwho-1508598

ABSTRACT

SARS-CoV-2 has infected hundreds of millions of people with over four million dead, resulting in one of the worst global pandemics in recent history. Neurological symptoms associated with COVID-19 include anosmia, ageusia, headaches, confusion, delirium, and strokes. These may manifest due to viral entry into the central nervous system (CNS) through the blood-brain barrier (BBB) by means of ill-defined mechanisms. Here, we summarize the abilities of SARS-CoV-2 and other neurotropic RNA viruses, including Zika virus and Nipah virus, to cross the BBB into the CNS, highlighting the role of magnetic resonance imaging (MRI) in assessing presence and severity of brain structural changes in COVID-19 patients. We present new insight into key mutations in SARS-CoV-2 variants B.1.1.7 (P681H) and B.1.617.2 (P681R), which may impact on neuropilin 1 (NRP1) binding and CNS invasion. We postulate that SARS-CoV-2 may infect both peripheral cells capable of crossing the BBB and brain endothelial cells to traverse the BBB and spread into the brain. COVID-19 patients can be followed up with MRI modalities to better understand the long-term effects of COVID-19 on the brain.


Subject(s)
Blood-Brain Barrier , Henipavirus Infections , Nipah Virus , SARS-CoV-2 , Zika Virus Infection , Zika Virus , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/physiopathology , Blood-Brain Barrier/virology , COVID-19/epidemiology , COVID-19/genetics , COVID-19/metabolism , COVID-19/physiopathology , Henipavirus Infections/epidemiology , Henipavirus Infections/genetics , Henipavirus Infections/metabolism , Henipavirus Infections/physiopathology , Humans , Mutation , Nipah Virus/genetics , Nipah Virus/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Zika Virus/genetics , Zika Virus/metabolism , Zika Virus Infection/epidemiology , Zika Virus Infection/genetics , Zika Virus Infection/metabolism , Zika Virus Infection/physiopathology
5.
Placenta ; 115: 70-77, 2021 11.
Article in English | MEDLINE | ID: covidwho-1433733

ABSTRACT

Species differences are among the main reasons for the high failure rate of preclinical studies. A better awareness and understanding of these differences might help to improve the outcome of preclinical research. In reproduction, the placenta is the central organ regulating fetal exposure to a substance circulating in the maternal organism. Exact information about placental transfer can help to better estimate the toxic potential of a substance. From an evolutionary point of view, the chorioallantoic placenta is the organ with the highest anatomical diversity among species. Moreover, frequently used animal models in reproduction belong to rodents and lagomorphs, two groups that are characterized by the generation of an additional type of placenta, which is crucial for fetal development, but absent from humans: the inverted yolk sac placenta. Taken together, the translatability of placental transfer studies from laboratory animals to humans is challenging, which is supported by the fact that numerous species-dependent toxic effects are described in literature. Thus, reliable human-relevant data are frequently lacking and the toxic potential of chemicals and pharmaceuticals for humans can hardly be estimated, often resulting in recommendations that medical treatments or exposure to chemicals should be avoided for safety reasons. Although species differences of placental anatomy have been described frequently and the need for human-relevant research models has been emphasized, analyses of substances with species-dependent placental transfer have been performed only sporadically. Here, we present examples for species-specific placental transfer, including that of nanoparticles and pharmaceuticals, and discuss potential underlying mechanisms. With respect to the COVID 19-pandemic it might be of interest that some antiviral drugs are reported to feature species-specific placental transfer. Further, differences in placental structure and antibody transfer may affect placental transfer of ZIKA virus.


Subject(s)
Maternal-Fetal Exchange/physiology , Placenta/metabolism , Animals , Antiviral Agents/pharmacokinetics , Biological Transport/physiology , COVID-19/drug therapy , COVID-19/transmission , COVID-19/virology , Female , Humans , Infectious Disease Transmission, Vertical , Maternal-Fetal Exchange/drug effects , Placenta/drug effects , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/metabolism , Pregnancy Complications, Infectious/virology , SARS-CoV-2/metabolism , Species Specificity , Yolk Sac/metabolism , Yolk Sac/physiology , Zika Virus/metabolism , Zika Virus Infection/drug therapy , Zika Virus Infection/transmission
6.
Biochim Biophys Acta Mol Basis Dis ; 1867(11): 166218, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1323748

ABSTRACT

Throughout history, pandemics of infectious diseases caused by emerging viruses have spread worldwide. Evidence from previous outbreaks demonstrated that pregnant women are at high risk of contracting the diseases and suffering from adverse outcomes. However, while some viruses can cause major health complications for the mother and her fetus, others do not appear to affect pregnancy. Viral surface proteins bind to specific receptors on the cellular membrane of host cells and begin therewith the infection process. During pregnancy, the molecular features of these proteins may determine specific target cells in the placenta, which may explain the different outcomes. In this review, we display information on Variola, Influenza, Zika and Corona viruses focused on their surface proteins, effects on pregnancy, and possible target placental cells. This will contribute to understanding viral entry during pregnancy, as well as to develop strategies to decrease the incidence of obstetrical problems in current and future infections.


Subject(s)
Placenta/virology , Pregnancy Complications, Infectious/virology , Viral Envelope Proteins/metabolism , Virus Diseases/virology , Female , Humans , Placenta/metabolism , Pregnancy , Pregnancy Complications, Infectious/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Variola virus/metabolism , Variola virus/pathogenicity , Virus Diseases/metabolism , Zika Virus/metabolism , Zika Virus/pathogenicity
7.
Int J Mol Sci ; 22(1)2020 Dec 30.
Article in English | MEDLINE | ID: covidwho-1006614

ABSTRACT

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins' functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.


Subject(s)
Protein Processing, Post-Translational , RNA Virus Infections/enzymology , RNA Virus Infections/virology , RNA Viruses/metabolism , RNA Viruses/pathogenicity , Viral Proteins/metabolism , Acetylation , Chikungunya virus/metabolism , Coronavirus/metabolism , Coronavirus/pathogenicity , Cytopathogenic Effect, Viral , Glycosylation , HIV/metabolism , HIV/pathogenicity , Host Microbial Interactions , Humans , Phosphorylation , RNA Virus Infections/immunology , RNA Virus Infections/metabolism , RNA Viruses/immunology , Ubiquitination , Virus Replication/physiology , Zika Virus/metabolism , Zika Virus/pathogenicity
8.
Cells ; 10(3)2021 03 02.
Article in English | MEDLINE | ID: covidwho-1125490

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) that has resulted in the current pandemic. The lack of highly efficacious antiviral drugs that can manage this ongoing global emergency gives urgency to establishing a comprehensive understanding of the molecular pathogenesis of SARS-CoV-2. We characterized the role of the nucleocapsid protein (N) of SARS-CoV-2 in modulating antiviral immunity. Overexpression of SARS-CoV-2 N resulted in the attenuation of retinoic acid inducible gene-I (RIG-I)-like receptor-mediated interferon (IFN) production and IFN-induced gene expression. Similar to the SARS-CoV-1 N protein, SARS-CoV-2 N suppressed the interaction between tripartate motif protein 25 (TRIM25) and RIG-I. Furthermore, SARS-CoV-2 N inhibited polyinosinic: polycytidylic acid [poly(I:C)]-mediated IFN signaling at the level of Tank-binding kinase 1 (TBK1) and interfered with the association between TBK1 and interferon regulatory factor 3 (IRF3), subsequently preventing the nuclear translocation of IRF3. We further found that both type I and III IFN production induced by either the influenza virus lacking the nonstructural protein 1 or the Zika virus were suppressed by the SARS-CoV-2 N protein. Our findings provide insights into the molecular function of the SARS-CoV-2 N protein with respect to counteracting the host antiviral immune response.


Subject(s)
Coronavirus Nucleocapsid Proteins/metabolism , DEAD Box Protein 58/metabolism , Interferons/metabolism , Receptors, Immunologic/metabolism , SARS-CoV-2/metabolism , DEAD Box Protein 58/genetics , Host-Pathogen Interactions/genetics , Humans , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferon Type I/genetics , Interferon Type I/metabolism , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interferons/genetics , Orthomyxoviridae/genetics , Orthomyxoviridae/metabolism , Phosphoproteins/metabolism , Poly C/pharmacology , Poly I/pharmacology , Promoter Regions, Genetic , /metabolism , Receptors, Immunologic/genetics , SARS-CoV-2/genetics , Signal Transduction/drug effects , Signal Transduction/genetics , Transcription Factors/metabolism , Tripartite Motif Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Up-Regulation , Zika Virus/genetics , Zika Virus/metabolism
9.
PLoS Pathog ; 17(1): e1009033, 2021 01.
Article in English | MEDLINE | ID: covidwho-1012135

ABSTRACT

The p53 transcription factor plays a key role both in cancer and in the cell-intrinsic response to infections. The ORFEOME project hypothesized that novel p53-virus interactions reside in hitherto uncharacterized, unknown, or hypothetical open reading frames (orfs) of human viruses. Hence, 172 orfs of unknown function from the emerging viruses SARS-Coronavirus, MERS-Coronavirus, influenza, Ebola, Zika (ZIKV), Chikungunya and Kaposi Sarcoma-associated herpesvirus (KSHV) were de novo synthesized, validated and tested in a functional screen of p53 signaling. This screen revealed novel mechanisms of p53 virus interactions and two viral proteins KSHV orf10 and ZIKV NS2A binding to p53. Originally identified as the target of small DNA tumor viruses, these experiments reinforce the notion that all viruses, including RNA viruses, interfere with p53 functions. These results validate this resource for analogous systems biology approaches to identify functional properties of uncharacterized viral proteins, long non-coding RNAs and micro RNAs.


Subject(s)
Communicable Diseases, Emerging/virology , RNA Viruses/metabolism , Signal Transduction/genetics , Tumor Suppressor Protein p53/metabolism , Chikungunya virus/genetics , Chikungunya virus/metabolism , Coronavirus/genetics , Coronavirus/metabolism , Ebolavirus/genetics , Ebolavirus/metabolism , Herpesvirus 8, Human/genetics , Herpesvirus 8, Human/metabolism , Humans , Influenza A virus/genetics , Influenza A virus/metabolism , Open Reading Frames , RNA Viruses/genetics , Tumor Suppressor Protein p53/genetics , Viral Nonstructural Proteins/metabolism , Zika Virus/genetics , Zika Virus/metabolism
10.
Biopreserv Biobank ; 18(6): 561-569, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-919312

ABSTRACT

When a new virus emerges and causes a significant epidemic, the emergency response relies on diagnostics, surveillance, testing, and proposal of treatments if they exist, and also in the longer term, redirection of research efforts toward understanding the newly discovered pathogen. To serve these goals, viral biobanks play a crucial role. The European Virus Archive (EVA) is a network of biobanks from research laboratories worldwide that has combined into a common set of practices and mutually beneficial objectives to give scientists the tools that they need to study viruses in general, and also to respond to a pandemic caused by emerging viruses. Taking the most recent outbreaks of the Zika virus and SARS-CoV-2 as examples, by looking at who orders what and when to the EVA, we illustrate how the global science community at large, public health, fundamental research and private companies, reorganize their activity toward diagnosing, understanding, and fighting the new pathogen.


Subject(s)
Biological Specimen Banks , COVID-19 , Pandemics , SARS-CoV-2/metabolism , Zika Virus Infection , Zika Virus/metabolism , COVID-19/epidemiology , COVID-19/metabolism , Europe/epidemiology , Humans , Zika Virus Infection/epidemiology , Zika Virus Infection/metabolism
11.
Viruses ; 12(10)2020 10 21.
Article in English | MEDLINE | ID: covidwho-887617

ABSTRACT

Most cells can release extracellular vesicles (EVs), membrane vesicles containing various proteins, nucleic acids, enzymes, and signaling molecules. The exchange of EVs between cells facilitates intercellular communication, amplification of cellular responses, immune response modulation, and perhaps alterations in viral pathogenicity. EVs serve a dual role in inhibiting or enhancing viral infection and pathogenesis. This review examines the current literature on EVs to explore the complex role of EVs in the enhancement, inhibition, and potential use as a nanotherapeutic against clinically relevant viruses, focusing on neurotropic viruses: Zika virus (ZIKV) and human immunodeficiency virus (HIV). Overall, this review's scope will elaborate on EV-based mechanisms, which impact viral pathogenicity, facilitate viral spread, and modulate antiviral immune responses.


Subject(s)
Extracellular Vesicles/metabolism , Virus Diseases/metabolism , Antiviral Agents/pharmacology , Cell Communication/physiology , Coronavirus/metabolism , Coronavirus/pathogenicity , Exosomes/metabolism , HIV/metabolism , HIV/pathogenicity , HIV Infections/metabolism , Humans , Retroviridae/metabolism , Simplexvirus/metabolism , Therapeutics/methods , Virus Diseases/drug therapy , Virus Diseases/virology , Zika Virus/metabolism , Zika Virus/pathogenicity , Zika Virus Infection/metabolism
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