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1.
Cell ; 186(10): 2144-2159.e22, 2023 05 11.
Article in English | MEDLINE | ID: covidwho-2312256

ABSTRACT

Bats are special in their ability to live long and host many emerging viruses. Our previous studies showed that bats have altered inflammasomes, which are central players in aging and infection. However, the role of inflammasome signaling in combating inflammatory diseases remains poorly understood. Here, we report bat ASC2 as a potent negative regulator of inflammasomes. Bat ASC2 is highly expressed at both the mRNA and protein levels and is highly potent in inhibiting human and mouse inflammasomes. Transgenic expression of bat ASC2 in mice reduced the severity of peritonitis induced by gout crystals and ASC particles. Bat ASC2 also dampened inflammation induced by multiple viruses and reduced mortality of influenza A virus infection. Importantly, it also suppressed SARS-CoV-2-immune-complex-induced inflammasome activation. Four key residues were identified for the gain of function of bat ASC2. Our results demonstrate that bat ASC2 is an important negative regulator of inflammasomes with therapeutic potential in inflammatory diseases.


Subject(s)
Apoptosis Regulatory Proteins , Chiroptera , Inflammasomes , Ribonucleoproteins , Virus Diseases , Animals , Humans , Mice , Apoptosis Regulatory Proteins/metabolism , Chiroptera/immunology , COVID-19 , Inflammasomes/immunology , Ribonucleoproteins/metabolism , SARS-CoV-2 , Virus Diseases/immunology , Virus Physiological Phenomena
2.
J Am Assoc Lab Anim Sci ; 61(4): 344-352, 2022 07 01.
Article in English | MEDLINE | ID: covidwho-1975772

ABSTRACT

Bats are known natural reservoirs of several highly pathogenic zoonotic viruses, including Hendra virus, Nipah virus, rabies virus, SARS-like coronaviruses, and suspected ancestral reservoirs of SARS-CoV-2 responsible for the ongoing COVID-19 pandemic. The capacity to survive infections of highly pathogenic agents without severe disease, together with many other unique features, makes bats an ideal animal model for studying the regulation of infection, cancer, and longevity, which is likely to translate into human health outcomes. A key factor that limits bat research is lack of breeding bat colonies. To address this need, a captive bat colony was established in Singapore from 19 wild-caught local cave nectar bats. The bats were screened for specific pathogens before the start of captive breeding. Custom-made cages and an optimized diet inclusive of Wombaroo dietary formula, liquid diet, and supplement of fruits enabled the bats to breed prolifically in our facility. Cages are washed daily and disinfected once every fortnight. Bats are observed daily to detect any sick bat or abnormal behavior. In addition, bats undergo a thorough health check once every 3 to 4 mo to check on their overall wellbeing, perform sampling, and document any potential pregnancy. The current colony houses over 80 bats that are successfully breeding, providing a valuable resource for research in Singapore and overseas.


Subject(s)
COVID-19 , Chiroptera , Animals , Breeding , Disease Reservoirs , Humans , Pandemics , Phylogeny , Plant Nectar , SARS-CoV-2 , Singapore
3.
Infect Dis Ther ; 9(3): 669-675, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-635608

ABSTRACT

INTRODUCTION: As of 22 June 2020, Severe Acute Respiratory Syndrome (SARS)-coronavirus (CoV)-2 has infected more than 8.95 million people worldwide, causing > 468,000 deaths. The virus is transmitted through respiratory droplets and physical contact from contaminated surfaces to the mucosa. Hand hygiene and oral decontamination among other measures are key to preventing the spread of the virus. We report the in vitro virucidal activity of topical and oral povidone-iodine (PVP-I) products against SARS-CoV-2. METHODS: Suspension assays were used to assess the virucidal activity of PVP-I against SARS-CoV-2. Products were tested at a contact time of 30 s for virucidal activity. Viral titres were calculated using the Spearman-Kärber method and reported as median tissue culture infectious dose (TCID50)/mL. RESULTS: All four products [antiseptic solution (PVP-I 10%), skin cleanser (PVP-I 7.5%), gargle and mouth wash (PVP-I 1%) and throat spray (PVP-I 0.45%)] achieved ≥ 99.99% virucidal activity against SARS-CoV-2, corresponding to ≥ 4 log10 reduction of virus titre, within 30 s of contact. CONCLUSION: This study provides evidence of rapid and effective virucidal activity of PVP-I against SARS-CoV-2. PVP-I-based products are widely available for medical and personal use for hand hygiene and oral decontamination, and could be readily integrated into coronavirus disease, COVID-19, infection control measures in hospital and community settings.

4.
Emerg Microbes Infect ; 9(1): 1497-1505, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-595010

ABSTRACT

In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, multiple diagnostic tests are required for acute disease diagnosis, contact tracing, monitoring asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed. Unlike PCR tests which are highly specific, cross-reactivity is a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. SARS-CoV is genetically related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus in the genus Betacoronavirus of family Coronaviridae. We developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. There is significant cross-reactivity when N protein of either virus is used. The S1 or RBD regions from the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. We found that SARS survivors all have significant levels of antibodies remaining in their blood 17 years after infection. Anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Serologic Tests/methods , Severe Acute Respiratory Syndrome/diagnosis , Severe acute respiratory syndrome-related coronavirus/immunology , Antibodies, Viral/blood , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Coronavirus Nucleocapsid Proteins , Cross Reactions , Diagnosis, Differential , Enzyme-Linked Immunosorbent Assay/methods , HEK293 Cells , Humans , Immunoprecipitation , Nucleocapsid Proteins/immunology , Pandemics , Phosphoproteins , Protein Domains/immunology , Severe acute respiratory syndrome-related coronavirus/isolation & purification , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
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