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1.
Frontiers in Microbiology ; 13:997539, 2022.
Article in English | MEDLINE | ID: covidwho-2022796

ABSTRACT

Stress granule formation is induced by numerous environmental stressors, including sodium arsenite treatment and viral infection. Accordingly, stress granules can inhibit viral propagation and function as part of the antiviral host response to numerous viral infections. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antagonizes stress granule formation, in part, via interaction between SARS-CoV-2 nucleocapsid (N) protein and Ras-GTPase-activating SH3-domain-binding protein 1 (G3BP1). However, it is unclear whether there are differential effects in different cell types. In this study, we assessed interaction between the N protein of SARS-CoV-2 S clade and G3BP1/2 in Vero and Calu-3 cells and investigated the effect of various SARS-CoV-2 strains on sodium arsenite-induced stress granule formation. Our data show that SARS-CoV-2 S clade N protein interacts with both G3BP1 and G3BP2 more strongly in Calu-3 vs. Vero cells. Consistent with this observation, infection with SARS-CoV-2 S clade induces stress granule formation in Vero but not in Calu-3 cells. However, infection with SARS-CoV-2 S clade, as well as other SARS-CoV-2 variants, inhibits sodium arsenite-induced stress granule formation in both cell lines. Taken together, our results show differential effects of SARS-CoV-2 infection on stress granule formation that is dependent on host cell type, rather than virus strain type.

2.
Gastroenterology ; 162(7):S-600, 2022.
Article in English | EMBASE | ID: covidwho-1967347

ABSTRACT

Introduction Despite the global impact of the COVID-19 pandemic, vaccine hesitancy remains common in the general public. Adults who were on immunosuppressive medications were among the earlier groups recommended by the Centers for Disease Control and Prevention to receive the COVID-19 vaccine. It is unclear whether similar vaccine hesitancy is seen in patients with inflammatory bowel disease (IBD), especially those who are on immunosuppressive medications. We sought to examine rate of vaccine hesitancy in patients with IBD as well as associated demographic and socioeconomic risk factors. Methods We performed a retrospective chart review in November 2021 of 1383 patients with IBD seen at University of Maryland Medical Center, a tertiary referral medical center, between November 2020 and October 2021. Data obtained from patients' charts included demographics;disease characteristics including disease phenotype, number of years since diagnosis, number of IBD-related surgeries;and IBD therapy including biologics, thiopurines or methotrexate, corticosteroids, and mesalamine. Information on COVID vaccination and routinely recommended vaccines were also collected which included annual influenza vaccine, Prevnar/ Pneumovax, and Shingrix. Those with no recorded COVID-19 vaccine were contacted by nurses for updated vaccine status. Results 72% (990/1383) of patients in this cohort were on a biologic, 17% (232/1383) were on corticosteroids, and 16% (224/1383) were on thiopurine or methotrexate, indicating a cohort of patients with moderate to severe disease phenotype. Fifty-seven percent (792/1383) of patients received either the Pfizer, Moderna, or Johnson & Johnson vaccine. In a multivariate regression analysis, COVID vaccination was found to be positively associated with a number of factors including older age (p-value= 4.92e-4), female sex (p=1.61e-3), Asian and Caucasian races (p=9.13e-3, 6.47e-06), number of years since diagnosis (p=2.73e-2), number of clinic visits in the past 12 months (p= 2.66e-10), and biologic use (p=4.41e-4). This remained the case while controlling for IBD disease type;marital status;insurance (Commercial vs Medicaid vs Medicare);and tobacco, alcohol, and substance use history. Patients who received other routinely recommended vaccines (influenza, Prevnar/Pneumovax, Shingrix) were not more likely to receive COVID- 19 vaccine. Discussion Although majority of patients in this cohort were on an immunosuppressive medication, COVID-19 vaccination rate is only recorded to be at 57%. Number of clinic visits, presumably more education and conversation with healthcare providers, had a positive impact on COVID-19 vaccination. In this cohort, younger adults, males, and African Americans were less likely to receive COVID-19 vaccine. Healthcare providers need to recognize these potential risk factors for COVID-19 vaccine hesitancy.

3.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-334725

ABSTRACT

With the emergence of SARS-CoV-2 variants, there is urgent need to develop broadly neutralizing antibodies. Here, we isolate two V H H nanobodies (7A3 and 8A2) from dromedary camels by phage display, which have high affinity for the receptor-binding domain (RBD) and broad neutralization activities against SARS-CoV-2 and its emerging variants. Cryo-EM complex structures reveal that 8A2 binds the RBD in its up mode and 7A3 inhibits receptor binding by uniquely targeting a highly conserved and deeply buried site in the spike regardless of the RBD conformational state. 7A3 at a dose of a5 mg/kg efficiently protects K18-hACE2 transgenic mice from the lethal challenge of B.1.351 or B.1.617.2, suggesting that the nanobody has promising therapeutic potentials to curb the COVID-19 surge with emerging SARS-CoV-2 variants. ONE-SENTENCE SUMMARY: Dromedary camel ( Camelus dromedarius ) V H H phage libraries were built for isolation of the nanobodies that broadly neutralize SARS-CoV-2 variants.

4.
Advanced Electronic Materials ; 2022.
Article in English | Scopus | ID: covidwho-1708957

ABSTRACT

Sub-zero temperature sensors (SZTSs) have potential applications in safely storing COVID-19 vaccines. Herein, an SZTS based on laser-induced carbonization (LIC) achieved by a nanosecond infrared laser with a wavelength of 1064 nm is reported. Direct laser writing is adopted for laser-induced carbon in Kapton polyimide sheets with a thickness of 125 µm. The sensor exhibits a good linear change in resistance to sub-zero temperatures ranging from 0 to −150 °C, where the coefficient of determination adjusted R-square (R2) value is 0.99238, which indicates a good linear fit. The sensor exhibits a stable static response at all temperatures over time. The dynamic responses by controlling the liquid nitrogen gas and placing an ice cube on the sensor are also measured to validate the sensor. Notably, the electrical performance of the sensor remains stable even after 15 h. The sensor response of the LIC sample validates the 3D variable range-hopping charge transport mechanism, governed by the Mott equation with a good linear fit, which is mainly owing to disorder in its structure. LIC-based SZTSs can enable sensors that are ultra-fast to fabricate, roll-to-roll processable, economical, and more significantly, can be interfaced with flexible printed circuit boards without any additional interfacing. © 2022 Wiley-VCH GmbH

5.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-292966

ABSTRACT

With the emergence of SARS-CoV-2 variants, there is urgent need to develop broadly neutralizing antibodies. Here, we isolate two V H H nanobodies (7A3 and 8A2) from dromedary camels by phage display, which have high affinity for the receptor-binding domain (RBD) and broad neutralization activities against SARS-CoV-2 and its emerging variants. Cryo-EM complex structures reveal that 8A2 binds the RBD in its up mode and 7A3 inhibits receptor binding by uniquely targeting a highly conserved and deeply buried site in the spike regardless of the RBD conformational state. 7A3 at a dose of a5 mg/kg efficiently protects K18-hACE2 transgenic mice from the lethal challenge of B.1.351 or B.1.617.2, suggesting that the nanobody has promising therapeutic potentials to curb the COVID-19 surge with emerging SARS-CoV-2 variants. One-Sentence Summary: Dromedary camel ( Camelus dromedarius ) V H H phage libraries were built for isolation of the nanobodies that broadly neutralize SARS-CoV-2 variants.

6.
BMB reports ; 09:09, 2021.
Article in English | MEDLINE | ID: covidwho-1173250

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus disease 2019 (COVID-19) and may increase the risk of adverse outcomes in lung cancer patients. In this study, we investigated the expression and function of mucin 1 (MUC1) after SARS-CoV-2 infection in the lung epithelial cancer cell line Calu-3. MUC1 is a major constituent of the mucus layer in the respiratory tract and contributes to pathogen defense. SARS-CoV-2 infection induced MUC1 C-terminal subunit (MUC1-C) expression in a STAT3 activation-dependent manner. Inhibition of MUC1-C signaling increased apoptosis-related protein levels and reduced proliferation-related protein levels;however, SARS-CoV-2 replication was not affected. Together, these results suggest that increased MUC1-C expression in response to SARS-CoV-2 infection may trigger the growth of lung cancer cells, and COVID-19 may be a risk factor for lung cancer patients.

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