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1.
Journal of Medical Virology ; 02:02, 2022.
Article in English | MEDLINE | ID: covidwho-2013637

ABSTRACT

Increasing evidence supports inter-species transmission of SARS-CoV-2 variants from human to domestic or wild animals during the ongoing COVID-19 pandemic, which is posing great challenges to epidemic control. Clarifying the host range of emerging SARS-CoV-2 variants will provide instructive information for the containment of viral spillover. The spike protein (S) of SARS-CoV-2 is the key determinant of receptor utilization, and therefore amino acid mutations on S will probably alter viral host range. Here, in order to evaluate the impact of S mutations, we constructed 20 Hela cell lines stably expressing ACE2 orthologs from different animals, and prepared 27 pseudotyped SARS-CoV-2 carrying different spike mutants, among which 20 bear single mutation and the other 7 were cloned from emerging SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (B.1.429) and Mu (B.1.621). Using pseudoviral reporter assay, we identified that the substitutions of T478I and N501Y enabled the pseudovirus to utilize chicken ACE2, indicating potential infectivity to avian species. Furthermore, the S mutants of real SARS-CoV-2 variants comprising N501Y showed significantly acquired abilities to infect cells expressing mouse ACE2, indicating a critical role of N501Y in expanding SARS-CoV-2 host range. In addition, A262S and T478I significantly enhanced the utilization of various mammals ACE2. In summary, our results indicated that T478I and N501Y substitutions were two S mutations important for receptor adaption of SARS-CoV-2, potentially contributing to the spillover of the virus to many other animal hosts. Therefore, more attention should be paid to SARS-CoV-2 variants with these two mutations. This article is protected by copyright. All rights reserved.

3.
Microbiology Spectrum ; : e0105622, 2022.
Article in English | MEDLINE | ID: covidwho-2001788

ABSTRACT

Infection by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has posed a severe threat to global public health. The current study revealed that several inhibitors of protein kinases C (PKCs) possess protective activity against SARS-CoV-2 infection. Four pan-PKC inhibitors, Go 6983, bisindolylmaleimide I, enzastaurin, and sotrastaurin, reduced the replication of a SARS-CoV-2 replicon in both BHK-21 and Huh7 cells. A PKCdelta-specific inhibitor, rottlerin, was also effective in reducing viral infection. The PKC inhibitors acted at an early step of SARS-CoV-2 infection. Finally, PKC inhibitors blocked the replication of wild-type SARS-CoV-2 in ACE2-expressing A549 cells. Our work highlights the importance of the PKC signaling pathway in infection by SARS-CoV-2 and provides evidence that PKC-specific inhibitors are potential therapeutic agents against SARS-CoV-2. IMPORTANCE There is an urgent need for effective therapeutic drugs to control the pandemic caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). We found that several inhibitors of protein kinases C (PKCs) dramatically decrease the replication of SARS-CoV-2 in cultured cells. These PKC inhibitors interfere with an early step of viral infection. Therefore, the rapid and prominent antiviral effect of PKC inhibitors underscores that they are promising antiviral agents and suggests that PKCs are important host factors involved in infection by SARS-CoV-2.

4.
Journal of Organizational and End User Computing ; 34(6):22, 2022.
Article in English | Web of Science | ID: covidwho-1822481

ABSTRACT

This study focuses on the restorative effects of immersive virtual reality (VR) forest experiences on elderly people during the COVID-19 lockdown. A field experiment with 63 elderly participants was conducted in an elderly care institution in China. The results showed that a five-minute VR forest experience with three minutes of subsequent reliving can bring immediate psychological improvements (i.e., increased positive affect, decreased negative affect, and enhanced stress recovery) to elderly individuals. The negative affect decrease and stress recovery enhancement were more obvious among introverted individuals. Furthermore, participating in three VR forest experiences over three consecutive days can bring continuous psychological improvements. Moreover, short VR forest experiences were unable to significantly decrease the blood pressure of participants. The effects of three VR experiences over three days on blood pressure improvement were also nonsignificant. Additionally, VR forest experiences can increase elderly participants' intentions to undertake real forest therapy.

5.
MEDLINE; 2020.
Preprint in English | MEDLINE | ID: ppcovidwho-329976

ABSTRACT

COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of the century after severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) since 2012. Treatment options for CoVs are largely lacking. Here, we show that clofazimine, an anti-leprosy drug with a favorable safety and pharmacokinetics profile, possesses pan-coronaviral inhibitory activity, and can antagonize SARS-CoV-2 replication in multiple in vitro systems, including the human embryonic stem cell-derived cardiomyocytes and ex vivo lung cultures. The FDA-approved molecule was found to inhibit multiple steps of viral replication, suggesting multiple underlying antiviral mechanisms. In a hamster model of SARS-CoV-2 pathogenesis, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and fecal viral shedding, and also prevented cytokine storm associated with viral infection. Additionally, clofazimine exhibited synergy when administered with remdesivir. Since clofazimine is orally bioavailable and has a comparatively low manufacturing cost, it is an attractive clinical candidate for outpatient treatment and remdesivir-based combinatorial therapy for hospitalized COVID-19 patients, particularly in developing countries. Taken together, our data provide evidence that clofazimine may have a role in the control of the current pandemic SARS-CoV-2, endemic MERS-CoV in the Middle East, and, possibly most importantly, emerging CoVs of the future.

6.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326792

ABSTRACT

The devastation caused by SARS-CoV-2 has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses and thus its promise as an agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses, but also uncovered a new antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.

7.
China Information ; : 20, 2022.
Article in English | Web of Science | ID: covidwho-1677468

ABSTRACT

For some years now, there has been an increase in the number of Chinese students travelling abroad to pursue higher education. The outbreak of COVID-19 has created new challenges for international students around the world. Based on an analysis of online forums during the pandemic (January-July 2020), we focus on the challenges Chinese transnational students have been facing. From the state's point of view, being at the front of China's internationalization progress, the students are expected to have both a 'vision of globalization' ((sic)(sic)(sic)(sic)野) as well as a deep 'Chinese feeling' ((sic)(sic)(sic)(sic)). However, in practice during the pandemic, the students found it extremely difficult to achieve a balance between their multiple identities. In this article, we argue that discrepancies between the students' identities may be due to the pandemic having highlighted several existing conflicts that have so far received only meagre attention or were even overlooked.

8.
International Journal of Customer Relationship Marketing and Management ; 13(1), 2022.
Article in English | Scopus | ID: covidwho-1481072

ABSTRACT

This study investigates the mediated moderating relationship of self-concept clarity, materialism, and social consumption motivation in the context of COVID-19 pandemic based on the terror management theory. The findings suggest that Malaysian consumers have high self-concept clarity about their materialistic orientation. This materialistic orientation may be of hedonistic-utilitarian nature that is internally directed for self-satisfaction and not exclusively directed externally in material consumption to portray an image to others. Furthermore, this study posits that cultural factors like collectivism and uncertainty avoidance delimits the applicability of terror management theory in Malaysia, suggesting that the development of the theory draw heavily from Western ideology of individualism not directly relevant in the Asian context. Finally, this study offers an understanding of the self-concept clarity from the Asian context, addressing the appeal by Dunlop to investigate the construct of self-concept clarity particularly in non-Western context. Copyright © 2022, IGI Global.

9.
Journal of Aerosol Medicine and Pulmonary Drug Delivery ; 34(3):A4-A5, 2021.
Article in English | EMBASE | ID: covidwho-1338646

ABSTRACT

In response to emerging and re-emerging respiratory viral infections with high morbidity and mortality such as Coronavirus Disease 2019 (COVID-19), Middle East respiratory syndrome coronavirus (MERS-CoV), and influenza, early administration of broad-spectrum antivirals can facilitate pandemic control and improve patient outcomes. This provides empiric therapeutic options during the time-lag for developing specific drug/vaccine. AM80 (tamibarotene), an orally active retinoid, was demonstrated with broad-spectrum antiviral efficacy in a recent study. To maximise antiviral efficacy in respiratory tract, an inhalable powder formulation of AM80 was developed by spray freeze drying (SFD) technology with hydroxypropyl-bcyclodextrin (HPbCD) as solubiliser. The formulation showed good aerosol performance, as evaluated by Next Generation Impactor, with a fine particle fraction of 65.1 ± 7.9% and an emitted fraction of 95.1 ± 1.7%. The sublimation of solvent crystal led to the formation of porous particles, which was visualised by scanning electron microscopy. In contrast to the slow-dissolving unformulated AM80, the SFD AM80 powder displayed a burst-release dissolution, which is postulated to be a combined result of enhanced solubility by HPbCD and increased surface area of porous structure. The in vivo pharmacokinetics of the SFD AM80 powder after intratracheal administration was investigated in mice. With the same dose given, inhaled AM80 powder resulted in higher bioavailability in both lungs and plasma than intraperitoneally injected unformulated AM80 in 0.1% DMSO solution. This study demonstrated a strategy to develop an inhaled formulation for a broad-spectrum antiviral agent, which could be a strong candidate in clinical applications for various respiratory viral infections.

10.
CMES - Computer Modeling in Engineering and Sciences ; 127(2):385-387, 2021.
Article in English | Scopus | ID: covidwho-1215891
11.
Diagnostics ; 11(4):20, 2021.
Article in English | MEDLINE | ID: covidwho-1209020

ABSTRACT

Lung sounds remain vital in clinical diagnosis as they reveal associations with pulmonary pathologies. With COVID-19 spreading across the world, it has become more pressing for medical professionals to better leverage artificial intelligence for faster and more accurate lung auscultation. This research aims to propose a feature engineering process that extracts the dedicated features for the depthwise separable convolution neural network (DS-CNN) to classify lung sounds accurately and efficiently. We extracted a total of three features for the shrunk DS-CNN model: the short-time Fourier-transformed (STFT) feature, the Mel-frequency cepstrum coefficient (MFCC) feature, and the fused features of these two. We observed that while DS-CNN models trained on either the STFT or the MFCC feature achieved an accuracy of 82.27% and 73.02%, respectively, fusing both features led to a higher accuracy of 85.74%. In addition, our method achieved 16 times higher inference speed on an edge device and only 0.45% less accuracy than RespireNet. This finding indicates that the fusion of the STFT and MFCC features and DS-CNN would be a model design for lightweight edge devices to achieve accurate AI-aided detection of lung diseases.

12.
Non-conventional | WHO COVID | ID: covidwho-62

ABSTRACT

A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike's receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection. FAU - Chan, Jasper Fuk-Woo

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