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1.
J Leukoc Biol ; 111(2): 497-508, 2022 02.
Article in English | MEDLINE | ID: covidwho-1669515

ABSTRACT

Coronaviruses (CoVs) are RNA viruses that cause human respiratory infections. Zoonotic transmission of the SARS-CoV-2 virus caused the recent COVID-19 pandemic, which led to over 2 million deaths worldwide. Elevated inflammatory responses and cytotoxicity in the lungs are associated with COVID-19 severity in SARS-CoV-2-infected individuals. Bats, which host pathogenic CoVs, operate dampened inflammatory responses and show tolerance to these viruses with mild clinical symptoms. Delineating the mechanisms governing these host-specific inflammatory responses is essential to understand host-virus interactions determining the outcome of pathogenic CoV infections. Here, we describe the essential role of inflammasome activation in determining COVID-19 severity in humans and innate immune tolerance in bats that host several pathogenic CoVs. We further discuss mechanisms leading to inflammasome activation in human SARS-CoV-2 infection and how bats are molecularly adapted to suppress these inflammasome responses. We also report an analysis of functionally important residues of inflammasome components that provide new clues of bat strategies to suppress inflammasome signaling and innate immune responses. As spillover of bat viruses may cause the emergence of new human disease outbreaks, the inflammasome regulation in bats and humans likely provides specific strategies to combat the pathogenic CoV infections.


Subject(s)
COVID-19/pathology , Immune Tolerance , Immunity, Innate , Inflammasomes/immunology , SARS-CoV-2/immunology , Animals , COVID-19/immunology , COVID-19/virology , Chiroptera , Humans , Inflammasomes/metabolism , Phylogeny
2.
Minerva Stomatol ; 69(5): 324-327, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1267021

ABSTRACT

A new pandemic classified by the World Health Organization and called COVID-19, is causing widespread respiratory infections and deaths in several countries on the five continents. Although it does not have a high lethality rate, this new virus can present rates of complications and hospitalizations in the intensive care unit in up to 20% of patients, especially the elderly and those with compromised health, which can cause a collapse in the health system national public health. Dentistry is one of the most vulnerable professions due to work in the oral cavity, one of the areas with the highest concentration of the virus, therefore having an important role in controlling the disease. The objective of this work is through a review of the current literature, to establish conducts that can reduce the contamination by COVID-19 between the population and the dental team during the service in the public and private health system.


Subject(s)
Betacoronavirus , Coronavirus Infections , Dental Care , Pandemics , Pneumonia, Viral , Aged , COVID-19 , Coronavirus Infections/epidemiology , Humans , Infection Control , SARS-CoV-2
3.
Turk Kardiyol Dern Ars ; 49(4): 334-338, 2021 06.
Article in English | MEDLINE | ID: covidwho-1262653

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global coronavirus disease 2019 (COVID-19) pandemic. Although the virus predominantly causes respiratory system infection, recent reports have shown that it is also associated with many cardiovascular complications. It has been reported that COVID-19 may cause myocarditis, type 1 and 2 acute myocardial infarction, and thrombotic complications.[1] Spontaneous coronary artery dissection (SCAD) is a rare form of coronary artery disease that has recently been associated with COVID-19 in a few case reports. The case reported here is of COVID-19 associated SCAD in a patient with no history of cardiovascular disease.


Subject(s)
COVID-19/complications , Coronary Artery Disease , Coronary Vessel Anomalies , Vascular Diseases/congenital , Coronary Artery Disease/physiopathology , Coronary Artery Disease/therapy , Coronary Artery Disease/virology , Coronary Vessel Anomalies/physiopathology , Coronary Vessel Anomalies/therapy , Coronary Vessel Anomalies/virology , Electrocardiography , Humans , Male , Middle Aged , Vascular Diseases/physiopathology , Vascular Diseases/therapy , Vascular Diseases/virology
4.
Annu Rev Virol ; 8(1): 393-414, 2021 09 29.
Article in English | MEDLINE | ID: covidwho-1255635

ABSTRACT

Biological sex affects the outcome of diverse respiratory viral infections. The pathogenesis of respiratory infections caused by viruses ranging from respiratory syncytial virus to influenza viruses and severe acute respiratory syndrome coronavirus 2 differs between the sexes across the life course. Generally, males are more susceptible to severe outcomes from respiratory viral infections at younger and older ages. During reproductive years (i.e., after puberty and prior to menopause), females are often at greater risk than males for severe outcomes. Pregnancy and biological sex affect the pathogenesis of respiratory viral infections. In addition to sex differences in the pathogenesis of disease, there are consistent sex differences in responses to treatments, with females often developing greater immune responses but experiencing more adverse reactions than males. Animal models provide mechanistic insights into the causes of sex differences in respiratory virus pathogenesis and treatment outcomes, where available.


Subject(s)
Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/therapy , Virus Physiological Phenomena , Age Factors , Animals , Female , Humans , Male , Respiratory Tract Infections/immunology , Respiratory Tract Infections/virology , Severity of Illness Index , Sex Characteristics , Sex Factors , Viruses/classification
5.
Foods ; 10(4)2021 Apr 20.
Article in English | MEDLINE | ID: covidwho-1241257

ABSTRACT

Influenza A virus induces severe respiratory tract infection and results in a serious global health problem. Influenza infection disturbs the cross-talk connection between lung and gut. Probiotic treatment can inhibit influenza virus infection; however, the mechanism remains to be explored. The mice received Lactobacillus mucosae 1025, Bifidobacterium breve CCFM1026, and their mixture MIX for 19 days. Effects of probiotics on clinical symptoms, immune responses, and gut microbial alteration were evaluated. L. mucosae 1025 and MIX significantly reduced the loss of body weight, pathological symptoms, and viral loading. B. breve CCFM1026 significantly reduced the proportion of neutrophils and increased lymphocytes, the expressions of TLR7, MyD88, TRAF6, and TNF-α to restore the immune disorders. MIX increased the antiviral protein MxA expression, the relative abundances of Lactobacillus, Mucispirillum, Adlercreutzia, Bifidobacterium, and further regulated SCFA metabolism resulting in an enhancement of butyrate. The correlation analysis revealed that the butyrate was positively related to MxA expression (p < 0.001) but was negatively related to viral loading (p < 0.05). The results implied the possible antiviral mechanisms that MIX decreased viral loading and increased the antiviral protein MxA expression, which was closely associated with the increased butyrate production resulting from gut microbial alteration.

6.
J Virol Methods ; 294: 114183, 2021 08.
Article in English | MEDLINE | ID: covidwho-1225322

ABSTRACT

BACKGROUND: The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the worldwide coronavirus disease-19 (COVID-19) pandemic, starting in late 2019. The standard diagnostic methods to detect SARS-CoV-2 are PCR-based genetic assays. Antigen-antibody-based immunochromatographic assays are alternative methods of detecting this virus. Rapid diagnosis kits to detect SARS-CoV-2 are urgently needed. STUDY DESIGN: Three monoclonal antibodies against SARS-CoV-2 nucleocapsid (N) protein were used to develop an antigen-antibody-based immunochromatographic kit to detect SARS-CoV-2. These assays were evaluated using  nasopharyngeal swab specimens collected from patients suspected of having COVID-19. RESULTS: These assays detected recombinant SARS-CoV-2 N protein at concentrations >0.2 ng/mL within 10 min after protein loading, but did not detect the N proteins of Middle East respiratory syndrome coronavirus (MERS-CoV), human coronaviruses OC43 (HCoV-OC43) and 299E (HCoV-229E) and other pathogens causing respiratory infections. Nasopharyngeal swab specimens obtained 1~3, 4~9, and ≥ 10 days after symptom onset from COVID-19 patients diagnosed by RT-PCR showed positivity rates of 100 %, >80 %, and <30 %, respectively. CONCLUSIONS: Kits using this immunochromatographic assay may be a rapid and useful tool for point-of-care diagnosis of COVID-19 when samples are obtained from patients 1~9 days after symptom onset.


Subject(s)
COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/immunology , Immunoassay/methods , Animals , Antibodies, Monoclonal/immunology , COVID-19/blood , Humans , Nasopharynx/virology , Phosphoproteins/immunology , Rats , SARS-CoV-2
7.
Nutrients ; 13(5)2021 May 04.
Article in English | MEDLINE | ID: covidwho-1224078

ABSTRACT

Coronaviruses are a large family of viruses that are known to cause respiratory tract infections ranging from colds to more severe diseases, such as Middle East Respiratory Syndrome (MERS) and the Severe Acute Respiratory Syndrome (SARS). New Coronavirus Disease 2019 (COVID-19), which led to deaths as well as social and economic disruptions, is an ongoing worldwide pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Currently, there is no approved treatment for COVID-19. Hence, only supportive care has been approved by the World Health Organization (WHO) for now. Pharmacological agents used for the adjunctive treatment of COVID-19 following the current literature and clinical experiences include antiviral, anti-inflammatory, and anti-malaria drugs, and other traditional or untraditional treatments. However, it has been reported that the use of these drugs may have some negative effects and comorbidities. Moreover, the current data have indicated that the risk of drug-drug interactions may also be high in polypharmacy cases, especially in elderly people, some comorbidity situations, and intensive care unit (ICU) patients. It is highly possible that these situations can not only increase the risk of drug-drug interactions but also increase the risk of food/nutrition-drug interactions and affect the nutritional status. However, this issue has not yet been entirely discussed in the literature. In this review, current information on the possible mechanisms as well as pharmacokinetic and pharmacodynamic effects of some pharmacological agents used in the treatment of COVID-19 and/or their secondary interactions with nutrition were evaluated and some future directions were given.


Subject(s)
Antiviral Agents , COVID-19/drug therapy , Food-Drug Interactions , SARS-CoV-2 , Age Factors , Antiviral Agents/pharmacokinetics , Antiviral Agents/therapeutic use , COVID-19/epidemiology , Humans
8.
Virusdisease ; : 1-8, 2021 Apr 22.
Article in English | MEDLINE | ID: covidwho-1202859

ABSTRACT

Aerosol particles can spread respiratory infections, especially those caused by viruses; however, the perceived threat is small for many technical reasons, as identified in this article. Under controlled conditions, aerosol particles can travel up to a distance of 28 feet (or 8 m); however, such aerosol particles are less likely to have sufficient quantities of viable viruses to spread infection. Additionally, nearly all the experimental models examined the behavior of the aerosols only in confined spaces, not in open areas; these findings, therefore, cannot be considered generally applicable. In the absence of scientific information and education, only misconceptions, unfounded fears, and unsubstantiated myths will prevail. Given that an effective vaccine and drugs are still not available, prevention remains the only option of protection against SARS-CoV-2, the new coronavirus. Wearing a mask is not only necessary but also critical to reduce the probability of viral spread by contact (fomite), not aerosol, transmission.

9.
Rev Esp Quimioter ; 34(4): 365-370, 2021 Aug.
Article in Spanish | MEDLINE | ID: covidwho-1200529

ABSTRACT

OBJECTIVE: To control the pandemic caused by SARS-CoV-2, the implementation of social and hygienic confinement measures was determined in all countries. These measures reduce the circulation of most respiratory viruses that are transmitted preferentially by air and contact. METHODS: The impact of these measures on non-Covid respiratory viruses during the period August-December 2020 and 2019 has been comparatively analyzed. To all nasopharyngeal aspirates that were negative against SARS-CoV-2 by RT-PCR and the suspicion of acute respiratory infection persisted, were subjected to a new RT-PCR that simultaneously and differentially amplifies 21 different respiratory viruses. RESULTS: In the year of the pandemic, a 36.6% decrease was detected in the number of respiratory samples studied and 66% in their positivity in relation to 2019. All viruses showed reduction percentages of between 40-100%. The only viruses that circulated during and after national lockdown were rhinovirus (74.1%), adenovirus (10.1%), and enterovirus (9.6%). CONCLUSIONS: The measures used to control the SARS-CoV-2 infection have also affected the community circulation of most respiratory viruses including influenza and respiratory syncytial virus.


Subject(s)
COVID-19/prevention & control , Hygiene , Physical Distancing , Respiratory Tract Diseases/epidemiology , Virus Diseases/epidemiology , Communicable Disease Control , Humans , Influenza, Human/epidemiology , Nasopharynx/virology , Pandemics , Real-Time Polymerase Chain Reaction , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Tract Infections/epidemiology , Spain/epidemiology
10.
Inform Med Unlocked ; 24: 100577, 2021.
Article in English | MEDLINE | ID: covidwho-1193338

ABSTRACT

COVID-19 is an infectious disease caused by the newly discovered SARS-CoV-2 virus. This virus causes a respiratory tract infection, symptoms include dry cough, fever, tiredness and in more severe cases, breathing difficulty. SARS-CoV-2 is an extremely contagious virus that is spreading rapidly all over the world and the scientific community is working tirelessly to find an effective treatment. This paper aims to determine the origin of this virus by comparing its nucleic acid sequence with all members of the coronaviridae family. This study uses a new approach based on the combination of three powerful techniques which are: Ngrams (For text categorization), Principal Component Analysis (For dimensionality reduction) and Random Forest algorithm (For supervised classification). The experimental results have shown that a large set of SARS-CoV-2 genomes, collected from different locations around the world, present significant similarities to those found in pangolins. This finding confirms some previous results obtained by other methods, which also suggest that pangolins should be considered as possible hosts in the emergence of the new coronavirus.

11.
Emergent Mater ; : 1-26, 2021 Mar 25.
Article in English | MEDLINE | ID: covidwho-1160848

ABSTRACT

With the recent SARS-CoV-2 outbreak, the importance of rapid and direct detection of respiratory disease viruses has been well recognized. The detection of these viruses with novel technologies is vital in timely prevention and treatment strategies for epidemics and pandemics. Respiratory viruses can be detected from saliva, swab samples, nasal fluid, and blood, and collected samples can be analyzed by various techniques. Conventional methods for virus detection are based on techniques relying on cell culture, antigen-antibody interactions, and nucleic acids. However, these methods require trained personnel as well as expensive equipment. Microfluidic technologies, on the other hand, are one of the most accurate and specific methods to directly detect respiratory tract viruses. During viral infections, the production of detectable amounts of relevant antibodies takes a few days to weeks, hampering the aim of prevention. Alternatively, nucleic acid-based methods can directly detect the virus-specific RNA or DNA region, even before the immune response. There are numerous methods to detect respiratory viruses, but direct detection techniques have higher specificity and sensitivity than other techniques. This review aims to summarize the methods and technologies developed for microfluidic-based direct detection of viruses that cause respiratory infection using different detection techniques. Microfluidics enables the use of minimal sample volumes and thereby leading to a time, cost, and labor effective operation. Microfluidic-based detection technologies provide affordable, portable, rapid, and sensitive analysis of intact virus or virus genetic material, which is very important in pandemic and epidemic events to control outbreaks with an effective diagnosis.

13.
Pathogens ; 10(3)2021 Mar 08.
Article in English | MEDLINE | ID: covidwho-1143550

ABSTRACT

The aim of our study was to define the spectrum of viral infections in pilgrims with acute respiratory tract illnesses presenting to healthcare facilities around the holy places in Makkah, Saudi Arabia during the 2019 Hajj pilgrimage. During the five days of Hajj, a total of 185 pilgrims were enrolled in the study. Nasopharyngeal swabs (NPSs) of 126/185 patients (68.11%) tested positive for one or more respiratory viruses by PCR. Among the 126 pilgrims whose NPS were PCR positive: (a) there were 93/126 (74%) with a single virus infection, (b) 33/126 (26%) with coinfection with more than one virus (up to four viruses): of these, 25/33 cases had coinfection with two viruses; 6/33 were infected with three viruses, while the remaining 2/33 patients had infection with four viruses. Human rhinovirus (HRV) was the most common detected viruses with 53 cases (42.06%), followed by 27 (21.43%) cases of influenza A (H1N1), and 23 (18.25%) cases of influenza A other than H1N1. Twenty-five cases of CoV-229E (19.84%) were detected more than other coronavirus members (5 CoV-OC43 (3.97%), 4 CoV-HKU1 (3.17%), and 1 CoV-NL63 (0.79%)). PIV-3 was detected in 8 cases (6.35%). A single case (0.79%) of PIV-1 and PIV-4 were found. HMPV represented 5 (3.97%), RSV and influenza B 4 (3.17%) for each, and Parechovirus 1 (0.79%). Enterovirus, Bocavirus, and M. pneumoniae were not detected. Whether identification of viral nucleic acid represents nasopharyngeal carriage or specific causal etiology of RTI remains to be defined. Large controlled cohort studies (pre-Hajj, during Hajj, and post-Hajj) are required to define the carriage rates and the specific etiology and causal roles of specific individual viruses or combination of viruses in the pathogenesis of respiratory tract infections in pilgrims participating in the annual Hajj. Studies of the specific microbial etiology of respiratory track infections (RTIs) at mass gathering religious events remain a priority, especially in light of the novel SARS-CoV-2 pandemic.

14.
Nat Commun ; 12(1): 1653, 2021 03 12.
Article in English | MEDLINE | ID: covidwho-1132073

ABSTRACT

SARS-CoV-2 emerged in late 2019 and caused a pandemic, whereas the closely related SARS-CoV was contained rapidly in 2003. Here, an experimental set-up is used to study transmission of SARS-CoV and SARS-CoV-2 through the air between ferrets over more than a meter distance. Both viruses cause a robust productive respiratory tract infection resulting in transmission of SARS-CoV-2 to two of four indirect recipient ferrets and SARS-CoV to all four. A control pandemic A/H1N1 influenza virus also transmits efficiently. Serological assays confirm all virus transmission events. Although the experiments do not discriminate between transmission via small aerosols, large droplets and fomites, these results demonstrate that SARS-CoV and SARS-CoV-2 can remain infectious while traveling through the air. Efficient virus transmission between ferrets is in agreement with frequent SARS-CoV-2 outbreaks in mink farms. Although the evidence for virus transmission via the air between humans under natural conditions is absent or weak for SARS-CoV and SARS-CoV-2, ferrets may represent a sensitive model to study interventions aimed at preventing virus transmission.


Subject(s)
Air Microbiology , COVID-19/transmission , Ferrets/virology , SARS Virus , SARS-CoV-2 , Severe Acute Respiratory Syndrome/transmission , Aerosols , Amino Acid Substitution , Animal Fur/virology , Animals , COVID-19/virology , Disease Models, Animal , Female , Fomites/virology , Influenza A Virus, H1N1 Subtype , Models, Biological , Orthomyxoviridae Infections/transmission , Polymorphism, Single Nucleotide , SARS-CoV-2/genetics , Severe Acute Respiratory Syndrome/virology , Time Factors , Viral Load , Viral Zoonoses/transmission , Viral Zoonoses/virology , Virus Shedding
15.
Monaldi Arch Chest Dis ; 91(2)2021 Mar 05.
Article in English | MEDLINE | ID: covidwho-1119588

ABSTRACT

To the Editor An elegant study reported dysmorphic cells and syncytia in the deceased's lungs for COVID-19. The authors reasonably considered that most of these syncytia-forming cells were pneumocytes, as identified by specific biomarkers. However, cellular dysmorphism and syncytia are pathological features common in other respiratory infections caused by different viruses, including the human respiratory syncytial virus (HRSV) and Epstein-Barr virus (EBV), as correctly documented...


Subject(s)
COVID-19/pathology , Lung/pathology , Nose/pathology , Cilia/pathology , Epithelial Cells/pathology , Giant Cells/pathology , Humans
16.
Eur J Case Rep Intern Med ; 8(1): 002204, 2021.
Article in English | MEDLINE | ID: covidwho-1083855

ABSTRACT

The COVID-19 pandemic has posed new challenges for the scientific community. The behaviour of the virus and outcomes in people living with HIV have not yet been properly studied. We report the case of a 34-year-old man with newly diagnosed HIV infection stage 4 and asymptomatic SARS-CoV-2 infection. Although immunocompromised patients are classified as being at high risk of developing severe COVID-19, HIV-related immunosuppression may have a protective role. LEARNING POINTS: It is important to remember that not every respiratory infection during this pandemic is due to SARS-CoV-2.We need more studies to elucidate the behaviour of COVID-19 in people living with HIV.There is still doubt about the best time for antiretroviral therapy (ART) initiation in this context.

17.
Cell ; 184(1): 120-132.e14, 2021 01 07.
Article in English | MEDLINE | ID: covidwho-1064914

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of over one million people worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a member of the Coronaviridae family of viruses that can cause respiratory infections of varying severity. The cellular host factors and pathways co-opted during SARS-CoV-2 and related coronavirus life cycles remain ill defined. To address this gap, we performed genome-scale CRISPR knockout screens during infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E). These screens uncovered host factors and pathways with pan-coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, sterol regulatory element-binding protein (SREBP) signaling, bone morphogenetic protein (BMP) signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VMP1, TMEM41, and TMEM64 (VTT) domain-containing protein transmembrane protein 41B (TMEM41B) for infection by SARS-CoV-2 and three seasonal coronaviruses. This human coronavirus host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus pandemics.


Subject(s)
Coronavirus Infections/genetics , Genome-Wide Association Study , SARS-CoV-2/physiology , A549 Cells , Cell Line , Clustered Regularly Interspaced Short Palindromic Repeats , Coronavirus 229E, Human/physiology , Coronavirus Infections/virology , Coronavirus NL63, Human/physiology , Coronavirus OC43, Human/physiology , Gene Knockout Techniques , HEK293 Cells , Host-Pathogen Interactions/drug effects , Humans , Membrane Proteins/metabolism , Metabolic Networks and Pathways/drug effects , Protein Interaction Mapping
18.
Diabetes Metab Syndr ; 14(6): 1617-1619, 2020.
Article in English | MEDLINE | ID: covidwho-1059786

ABSTRACT

Coronaviruses are a large family of viruses that may cause illness in humans as well as in animals. In humans, coronaviruses cause respiratory infections ranging from the common cold to more severe diseases such as the Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). To combat this disease; various Nations have adopted many strategies across the globe. The present paper discuss the role and status of various countries related to wearing of masks by the public, as a crucial measure to minimize the spared of virus. Almost all the countries across the globe have favor the use of masks in public with several other measures. Thus, the use of masks in public is an important health measure and new normal after COVID-19 pandemic.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Internationality/legislation & jurisprudence , Masks/standards , Practice Guidelines as Topic/standards , Humans , Pandemics/prevention & control
19.
Ann Ig ; 33(1): 103-104, 2021.
Article in English | MEDLINE | ID: covidwho-1000569

ABSTRACT

The new Coronavirus is spreading rapidly around the world these days, and many countries are heavily infected with it. Corona is a large family of viruses that cause respiratory infections, from the common cold to the SARS epidemic that broke out in 2003, and now the newest member of the family (SARS-Cov-2) is present in Iran. Like other countries, it is expanding rapidly. Currently, COVID-19 pandemic is one of the most important health issues in Iran and around the World (1-4). The "Corona crisis" has led to various effects in the World, including economic, political, educational, cultural, lifestyle, and so on. But over time, the Corona outbreak appears to have led to an economic shock in the World. According to economists, there are three types of economic shocks caused by the virus; type L economic shock, in which economic growth slows and never improves; type U economic shock, in which economic growth decreases and subsequently improves, but never returns to its previous state; and type V economic shock, in which economic growth gradually decreases, but gradually returns to normal (5-8). It seems, in Iran, due to COVID-19 crisis, the hospitals as a heart of health services providing system were faced with the L type of economic shock.


Subject(s)
COVID-19/economics , Economics, Hospital , Pandemics/economics , SARS-CoV-2 , COVID-19/epidemiology , Developing Countries , Economic Recession , Economics, Hospital/statistics & numerical data , Humans , Iran/epidemiology
20.
Thorax ; 76(1): 64-72, 2021 01.
Article in English | MEDLINE | ID: covidwho-978826

ABSTRACT

INTRODUCTION: Human respiratory syncytial virus (HRSV) is a common cause of respiratory tract infections (RTIs) globally and is one of the most fatal infectious diseases for infants in developing countries. Of those infected, 25%-40% aged ≤1 year develop severe lower RTIs leading to pneumonia and bronchiolitis, with ~10% requiring hospitalisation. Evidence also suggests that HRSV infection early in life is a major cause of adult asthma. There is no HRSV vaccine, and the only clinically approved treatment is immunoprophylaxis that is expensive and only moderately effective. New anti-HRSV therapeutic strategies are therefore urgently required. METHODS: It is now established that viruses require cellular ion channel functionality to infect cells. Here, we infected human lung epithelial cell lines and ex vivo human lung slices with HRSV in the presence of a defined panel of chloride (Cl-) channel modulators to investigate their role during the HRSV life-cycle. RESULTS: We demonstrate the requirement for TMEM16A, a calcium-activated Cl- channel, for HRSV infection. Time-of-addition assays revealed that the TMEM16A blockers inhibit HRSV at a postentry stage of the virus life-cycle, showing activity as a postexposure prophylaxis. Another important negative-sense RNA respiratory pathogen influenza virus was also inhibited by the TMEM16A-specific inhibitor T16Ainh-A01. DISCUSSION: These findings reveal TMEM16A as an exciting target for future host-directed antiviral therapeutics.


Subject(s)
Anoctamin-1/pharmacology , Antibodies, Viral/immunology , Neoplasm Proteins/pharmacology , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus, Human/immunology , Cells, Cultured , Humans , Lung/metabolism , Lung/pathology , Lung/virology , Respiratory Syncytial Virus Infections/metabolism , Respiratory Syncytial Virus Infections/virology
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