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7.
Viruses ; 13(11)2021 10 26.
Article in English | MEDLINE | ID: covidwho-1488755

ABSTRACT

Understanding the dynamic relationship between viral pathogens and cellular host factors is critical to furthering our knowledge of viral replication, disease mechanisms and development of anti-viral therapeutics. CRISPR genome editing technology has enhanced this understanding, by allowing identification of pro-viral and anti-viral cellular host factors for a wide range of viruses, most recently the cause of the COVID-19 pandemic, SARS-CoV-2. This review will discuss how CRISPR knockout and CRISPR activation genome-wide screening methods are a robust tool to investigate the viral life cycle and how other class 2 CRISPR systems are being repurposed for diagnostics.


Subject(s)
CRISPR-Cas Systems , Communicable Diseases, Emerging/virology , Coronavirus Infections/virology , Coronavirus/genetics , Gene Editing , Zika Virus Infection/virology , Zika Virus/genetics , COVID-19/diagnosis , COVID-19/virology , Clustered Regularly Interspaced Short Palindromic Repeats , Communicable Diseases, Emerging/diagnosis , Coronavirus/physiology , Coronavirus Infections/diagnosis , Host-Pathogen Interactions , Humans , SARS-CoV-2/genetics , Zika Virus/physiology , Zika Virus Infection/diagnosis
8.
Med Mal Infect ; 50(3): 243-251, 2020 May.
Article in English | MEDLINE | ID: covidwho-1409419

ABSTRACT

Since the first case of human infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in June 2012, more than 2260 cases of confirmed MERS-CoV infection and 803 related deaths have been reported since the 16th of October 2018. The vast majority of these cases (71%) were reported in Saudi Arabia but the epidemic has now spread to 27 countries and has not ceased 6 years later, unlike SARS-CoV that disappeared a little less than 2 years after emerging. Due to the high fatality rate observed in MERS-CoV infected patients (36%), much effort has been put into understanding the origin and pathophysiology of this novel coronavirus to prevent it from becoming endemic in humans. This review focuses in particular on the origin, epidemiology and clinical manifestations of MERS-CoV, as well as the diagnosis and treatment of infected patients. The experience gained over recent years on how to manage the different risks related to this kind of epidemic will be key to being prepared for future outbreaks of communicable disease.


Subject(s)
Coronavirus Infections/virology , Middle East Respiratory Syndrome Coronavirus/physiology , Animals , Antiviral Agents/therapeutic use , Camelus/virology , Chiroptera/virology , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/prevention & control , Communicable Diseases, Emerging/virology , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Disease Management , Disease Reservoirs , Epidemics , Extracorporeal Membrane Oxygenation , Genome, Viral , Global Health , Humans , Hygiene , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Risk Factors , Saudi Arabia/epidemiology , Survival Rate , Symptom Assessment , Travel , Viral Vaccines
9.
Cell ; 184(6): 1604-1620, 2021 03 18.
Article in English | MEDLINE | ID: covidwho-1392179

ABSTRACT

Historically, emerging viruses appear constantly and have cost millions of human lives. Currently, climate change and intense globalization have created favorable conditions for viral transmission. Therefore, effective antivirals, especially those targeting the conserved protein in multiple unrelated viruses, such as the compounds targeting RNA-dependent RNA polymerase, are urgently needed to combat more emerging and re-emerging viruses in the future. Here we reviewed the development of antivirals with common targets, including those against the same protein across viruses, or the same viral function, to provide clues for development of antivirals for future epidemics.


Subject(s)
Antiviral Agents/therapeutic use , Communicable Diseases, Emerging/drug therapy , Communicable Diseases, Emerging/epidemiology , Molecular Targeted Therapy/methods , Pandemics , Virus Diseases/drug therapy , Virus Diseases/epidemiology , Viruses/enzymology , Animals , Antiviral Agents/pharmacology , Communicable Diseases, Emerging/virology , Humans , RNA-Dependent RNA Polymerase/antagonists & inhibitors , Viral Envelope Proteins/antagonists & inhibitors , Virus Diseases/virology , Virus Internalization/drug effects
10.
Cell Host Microbe ; 29(2): 160-164, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-1385266

ABSTRACT

The emergence of alternate variants of SARS-CoV-2 due to ongoing adaptations in humans and following human-to-animal transmission has raised concern over the efficacy of vaccines against new variants. We describe human-to-animal transmission (zooanthroponosis) of SARS-CoV-2 and its implications for faunal virus persistence and vaccine-mediated immunity.


Subject(s)
COVID-19/veterinary , Communicable Diseases, Emerging/veterinary , SARS-CoV-2/pathogenicity , Zoonoses/transmission , Zoonoses/virology , Animals , COVID-19/immunology , COVID-19/transmission , COVID-19/virology , Communicable Diseases, Emerging/transmission , Communicable Diseases, Emerging/virology , Disease Reservoirs/veterinary , Disease Reservoirs/virology , Humans , Immunity , Viral Vaccines/immunology
11.
Int Health ; 12(2): 77-85, 2020 02 12.
Article in English | MEDLINE | ID: covidwho-1387916

ABSTRACT

BACKGROUND: Strategies are urgently needed to mitigate the risk of zoonotic disease emergence in southern China, where pathogens with zoonotic potential are known to circulate in wild animal populations. However, the risk factors leading to emergence are poorly understood, which presents a challenge in developing appropriate mitigation strategies for local communities. METHODS: Residents in rural communities of Yunnan, Guangxi and Guangdong provinces were recruited and enrolled in this study. Data were collected through ethnographic interviews and field observations, and thematically coded and analysed to identify both risk and protective factors for zoonotic disease emergence at the individual, community and policy levels. RESULTS: Eighty-eight ethnographic interviews and 55 field observations were conducted at nine selected sites. Frequent human-animal interactions and low levels of environmental biosecurity in local communities were identified as risks for zoonotic disease emergence. Policies and programmes existing in the communities provide opportunities for zoonotic risk mitigation. CONCLUSIONS: This study explored the relationship among zoonotic risk and human behaviour, environment and policies in rural communities in southern China. It identifies key behavioural risk factors that can be targeted for development of tailored risk-mitigation strategies to reduce the threat of novel zoonoses.


Subject(s)
Animals, Wild/virology , Communicable Diseases, Emerging/transmission , Coronavirus Infections/transmission , Disease Outbreaks/prevention & control , Pneumonia, Viral/transmission , Rural Population , Virus Diseases/transmission , Zoonoses/transmission , Adolescent , Adult , Animals , Betacoronavirus , COVID-19 , China/epidemiology , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Female , Health Knowledge, Attitudes, Practice , Humans , Interviews as Topic , Male , Middle Aged , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Qualitative Research , Risk Factors , SARS-CoV-2 , Severe Acute Respiratory Syndrome , Virus Diseases/epidemiology , Young Adult , Zoonoses/epidemiology , Zoonoses/virology
13.
Viruses ; 13(8)2021 07 22.
Article in English | MEDLINE | ID: covidwho-1325789

ABSTRACT

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog populations. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralising antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Due to the retrospective nature of this study, samples for viral isolation and PCR were unavailable. Still, seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms.


Subject(s)
COVID-19/veterinary , Communicable Diseases, Emerging/veterinary , Dog Diseases/epidemiology , SARS-CoV-2/isolation & purification , Animals , Antibodies, Viral/blood , COVID-19/blood , COVID-19/epidemiology , COVID-19/virology , Communicable Diseases, Emerging/blood , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/virology , Croatia/epidemiology , Dog Diseases/blood , Dog Diseases/diagnosis , Dog Diseases/virology , Dogs , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Pandemics , Retrospective Studies , SARS-CoV-2/immunology , Seroepidemiologic Studies
15.
Viruses ; 13(6)2021 06 16.
Article in English | MEDLINE | ID: covidwho-1286940

ABSTRACT

Dengue fever, caused by the mosquito-borne dengue virus (DENV), has been endemic in Myanmar since 1970 and it has become a significant public health burden. It is crucial that circulating DENV strains are identified and monitored, and that their transmission efficiency and association with disease severity is understood. In this study, we analyzed DENV-1, DENV-2, DENV-3, and DENV-4 serotypes in 1235 serum samples collected in Myanmar between 2017 and 2019. Whole-genome sequencing of DENV-1-4 demonstrated that most DENV-1-4 strains had been circulating in Myanmar for several years. We also identified the emergence of DENV-3 genotype-I in 2017 samples, which persisted through 2018 and 2019. The emergence of the strain coincided with a period of increased DENV-3 cases and marked changes in the serotype dynamics. Nevertheless, we detected no significant differences between serum viral loads, disease severity, and infection status of individuals infected with different DENV serotypes during the 3-year study. Our results not only identify the spread of a new DENV-3 genotype into Yangon, Myanmar, but also support the importance of DENV evolution in changing the epidemic dynamics in endemic regions.


Subject(s)
Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/virology , Dengue Virus/classification , Dengue Virus/genetics , Dengue/epidemiology , Dengue/virology , Genotype , Adolescent , Amino Acid Substitution , Child , Child, Preschool , Dengue/diagnosis , Dengue/history , Dengue Virus/isolation & purification , Disease Outbreaks , Genetic Variation , Genome, Viral , History, 21st Century , Humans , Myanmar , Phylogeny , Seroepidemiologic Studies , Serogroup , Whole Genome Sequencing
16.
Viruses ; 13(6)2021 05 31.
Article in English | MEDLINE | ID: covidwho-1256669

ABSTRACT

Identification of therapeutics against emerging and re-emerging viruses remains a continued priority that is only reinforced by the recent SARS-CoV-2 pandemic. Advances in monoclonal antibody (mAb) isolation, characterization, and production make it a viable option for rapid treatment development. While mAbs are traditionally screened and selected based on potency of neutralization in vitro, it is clear that additional factors contribute to the in vivo efficacy of a mAb beyond viral neutralization. These factors include interactions with Fc receptors (FcRs) and complement that can enhance neutralization, clearance of infected cells, opsonization of virions, and modulation of the innate and adaptive immune response. In this review, we discuss recent studies, primarily using mouse models, that identified a role for Fc-FcγR interactions for optimal antibody-based protection against emerging and re-emerging virus infections.


Subject(s)
Communicable Diseases, Emerging/immunology , Immunoglobulin Fc Fragments/immunology , Receptors, IgG/immunology , Virus Diseases/immunology , Viruses/immunology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibody-Dependent Cell Cytotoxicity , Communicable Diseases, Emerging/therapy , Communicable Diseases, Emerging/virology , Humans , Immunization, Passive , Phagocytosis , Virus Diseases/therapy , Virus Diseases/virology , Viruses/classification
17.
PLoS Pathog ; 17(6): e1009583, 2021 06.
Article in English | MEDLINE | ID: covidwho-1256050

ABSTRACT

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic reveals a major gap in global biosecurity infrastructure: a lack of publicly available biological samples representative across space, time, and taxonomic diversity. The shortfall, in this case for vertebrates, prevents accurate and rapid identification and monitoring of emerging pathogens and their reservoir host(s) and precludes extended investigation of ecological, evolutionary, and environmental associations that lead to human infection or spillover. Natural history museum biorepositories form the backbone of a critically needed, decentralized, global network for zoonotic pathogen surveillance, yet this infrastructure remains marginally developed, underutilized, underfunded, and disconnected from public health initiatives. Proactive detection and mitigation for emerging infectious diseases (EIDs) requires expanded biodiversity infrastructure and training (particularly in biodiverse and lower income countries) and new communication pipelines that connect biorepositories and biomedical communities. To this end, we highlight a novel adaptation of Project ECHO's virtual community of practice model: Museums and Emerging Pathogens in the Americas (MEPA). MEPA is a virtual network aimed at fostering communication, coordination, and collaborative problem-solving among pathogen researchers, public health officials, and biorepositories in the Americas. MEPA now acts as a model of effective international, interdisciplinary collaboration that can and should be replicated in other biodiversity hotspots. We encourage deposition of wildlife specimens and associated data with public biorepositories, regardless of original collection purpose, and urge biorepositories to embrace new specimen sources, types, and uses to maximize strategic growth and utility for EID research. Taxonomically, geographically, and temporally deep biorepository archives serve as the foundation of a proactive and increasingly predictive approach to zoonotic spillover, risk assessment, and threat mitigation.


Subject(s)
Biological Specimen Banks/organization & administration , Communicable Disease Control , Communicable Diseases, Emerging/prevention & control , Community Networks/organization & administration , Public Health Surveillance/methods , Animals , Animals, Wild , Biodiversity , Biological Specimen Banks/standards , Biological Specimen Banks/supply & distribution , Biological Specimen Banks/trends , COVID-19/epidemiology , Communicable Disease Control/methods , Communicable Disease Control/organization & administration , Communicable Disease Control/standards , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/microbiology , Communicable Diseases, Emerging/virology , Community Networks/standards , Community Networks/supply & distribution , Community Networks/trends , Disaster Planning/methods , Disaster Planning/organization & administration , Disaster Planning/standards , Geography , Global Health/standards , Global Health/trends , Humans , Medical Countermeasures , Pandemics/prevention & control , Public Health , Risk Assessment , SARS-CoV-2/physiology , Zoonoses/epidemiology , Zoonoses/prevention & control
18.
Emerg Microbes Infect ; 10(1): 1227-1240, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1246665

ABSTRACT

The ongoing pandemic of COVID-19, caused by SARS-CoV-2, has severely impacted the global public health and socio-economic stability, calling for effective vaccines and therapeutics. In this study, we continued our efforts to develop more efficient SARS-CoV-2 fusion inhibitors and achieved significant findings. First, we found that the membrane-proximal external region (MPER) sequence of SARS-CoV-2 spike fusion protein plays a critical role in viral infectivity and can serve as an ideal template for design of fusion-inhibitory peptides. Second, a panel of novel lipopeptides was generated with greatly improved activity in inhibiting SARS-CoV-2 fusion and infection. Third, we showed that the new inhibitors maintained the potent inhibitory activity against emerging SARS-CoV-2 variants, including those with the major mutations of the B.1.1.7 and B.1.351 strains circulating in the United Kingdom and South Africa, respectively. Fourth, the new inhibitors also cross-inhibited other human CoVs, including SARS-CoV, MERS-CoV, HCoV-229E, and HCoV-NL63. Fifth, the structural properties of the new inhibitors were characterized by circular dichroism (CD) spectroscopy and crystallographic approach, which revealed the mechanisms underlying the high binding and inhibition. Combined, our studies provide important information for understanding the mechanism of SARS-CoV-2 fusion and a framework for the development of peptide therapeutics for the treatment of SARS-CoV-2 and other CoVs.


Subject(s)
Drug Design , Lipopeptides/chemical synthesis , Lipopeptides/pharmacology , SARS-CoV-2/drug effects , Virus Attachment/drug effects , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cell Fusion , Cell Survival/drug effects , Chlorocebus aethiops , Communicable Diseases, Emerging/virology , HEK293 Cells , Humans , Mutagenesis, Site-Directed , Protein Conformation , Vero Cells
19.
Cells ; 10(6)2021 05 23.
Article in English | MEDLINE | ID: covidwho-1243956

ABSTRACT

The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.


Subject(s)
Adaptive Immunity/genetics , Camelus/virology , Communicable Diseases, Emerging/immunology , Coronavirus Infections/immunology , Immunity, Innate/genetics , Zoonoses/immunology , Animals , Antibodies, Viral , Bronchi/cytology , Bronchi/physiology , COVID-19/genetics , COVID-19/immunology , COVID-19/virology , Camelus/genetics , Camelus/immunology , Cilia/physiology , Communicable Diseases, Emerging/genetics , Communicable Diseases, Emerging/transmission , Communicable Diseases, Emerging/virology , Coronavirus Infections/genetics , Coronavirus Infections/transmission , Coronavirus Infections/virology , Disease Reservoirs/virology , Female , Genetic Predisposition to Disease , Host Microbial Interactions/genetics , Host Microbial Interactions/immunology , Humans , Male , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Respiratory Mucosa/cytology , Respiratory Mucosa/physiology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , United Arab Emirates , Virus Replication/genetics , Virus Replication/immunology , Zoonoses/genetics , Zoonoses/transmission , Zoonoses/virology
20.
Cell ; 184(10): 2532-2534, 2021 05 13.
Article in English | MEDLINE | ID: covidwho-1229877

ABSTRACT

In this issue of Cell, Washington et al. and Alpert et al. demonstrate the value of genomic surveillance when studying the introduction of the B.1.1.7 variant to the US and illustrate the challenge that results from the lack of good sampling strategies.


Subject(s)
COVID-19/epidemiology , Communicable Diseases, Emerging/epidemiology , Epidemiological Monitoring , Metagenomics/methods , SARS-CoV-2/isolation & purification , COVID-19/virology , Communicable Diseases, Emerging/virology , Humans , SARS-CoV-2/genetics , United States/epidemiology
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