A5040481654- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Mosquito-borne diseases and control
- Bacteriophages and microbial interactions
- Viral Infections and Immunology Research
- Respiratory viral infections research
- interferon and immune responses
- COVID-19 epidemiological studies
- Long-Term Effects of COVID-19
- Influenza Virus Research Studies
- Circular RNAs in diseases
- Phagocytosis and Immune Regulation
- Viral Infections and Vectors
- Immune Cell Function and Interaction
- MicroRNA in disease regulation
- Immune responses and vaccinations
- Virology and Viral Diseases
- COVID-19 diagnosis using AI
- Liver Disease Diagnosis and Treatment
- PARP inhibition in cancer therapy
- Infection Control and Ventilation
- Endoplasmic Reticulum Stress and Disease
University of Hong Kong
2015-2024
Chinese University of Hong Kong
2015-2024
HKU-Pasteur Research Pole
2023
Xinyang College of Agriculture and Forestry
2023
Hong Kong Science and Technology Parks Corporation
2022
University of Pennsylvania
2021
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported from China in January, 2020. SARS-CoV-2 is efficiently transmitted person to and, months, has caused more than 82 000 laboratory-confirmed cases of disease 2019 (COVID-19) and 2800 deaths 46 countries. The total number surpassed that the 2003 severe (SARS-CoV). Although both COVID-19 (SARS) manifest as pneumonia, associated with apparently efficient transmission, fewer diarrhoea, increased mental confusion, a lower...
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging that has resulted in more than 000 laboratory-confirmed cases including over 145 deaths. Although SARS-CoV-2 and SARS-CoV share a number of common clinical manifestations, appears to be highly efficient person-to-person transmission frequently causes asymptomatic or presymptomatic infections. However, the underlying mechanisms confer these viral characteristics high transmissibility infection...
Lipids play numerous indispensable cellular functions and are involved in multiple steps the replication cycle of viruses. Infections by human-pathogenic coronaviruses result diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how lipids may modulate pathogenicity remains poor. To this end, we utilized human coronavirus 229E (HCoV-229E) as a model comprehensively characterize host cell lipid response...
Coronavirus tropism is predominantly determined by the interaction between coronavirus spikes and host receptors. In this regard, coronaviruses have evolved a complicated receptor-recognition system through their spike proteins. Spikes from highly related can recognize distinct receptors, whereas of distant employ same cell-surface molecule for entry. Moreover, broad range molecules in addition to receptors thereby augment attachment or The receptor Middle East respiratory syndrome...
Clinical manifestations of coronavirus disease 2019 (COVID-19) vary from asymptomatic virus shedding, nonspecific pharyngitis, to pneumonia with silent hypoxia and respiratory failure. Dendritic cells macrophages are sentinel for innate adaptive immunity that affect the pathogenesis severe acute syndrome (SARS) Middle East (MERS). The interplay between SARS-CoV-2 these cell types remains unknown. We investigated infection host responses monocyte-derived dendritic (moDCs) (MDMs) infected by...
Wildtype mice are not susceptible to SARS-CoV-2 infection. Emerging variants, including B.1.1.7, B.1.351, P.1, and P.3, contain mutations in spike that has been suggested associate with an increased recognition of mouse ACE2, raising the postulation these variants may have evolved expand species tropism wildtype potentially other murines. Our study evaluated this possibility substantial public health importance.
Abstract Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on transmissibility and pathogenesis, reveal targets intervention. Here, we analyze host viral determinants essential for in both lung epithelial ex vivo tissues. We identify heparan sulfate as an important attachment factor infection. Next, show sialic acids present ACE2 prevent spike/ACE2-interaction. While SARS-CoV is substantially limited by acid-mediated restriction...
SARS-CoV-2 B.1.1.529.1 (Omicron BA.1) emerged in November 2021 and quickly became the predominant circulating variant globally. Omicron BA.1 contains more than 30 mutations spike protein, which contribute to its altered virological features when compared ancestral or previous variants. Recent studies by us others demonstrated that is less dependent on transmembrane serine protease 2 (TMPRSS2), efficient cleavage, fusogenic, adopts an propensity utilize plasma membrane endosomal pathways for...
Abstract Emerging SARS-CoV-2 variants, particularly the Omicron variant and its sublineages, continually threaten global public health. Small molecule antivirals are an effective treatment strategy to fight against virus. However, first-generation either show limited clinical efficacy and/or have some defects in pharmacokinetic (PK) properties. Moreover, with increased use of these drugs across globe, they face great pressure drug resistance. We herein present discovery characterization a...
Infection by highly pathogenic coronaviruses results in substantial apoptosis. However, the physiological relevance of apoptosis pathogenesis coronavirus infections is unknown. Here, with a combination vitro, ex vivo, and vivo models, we demonstrated that protein kinase R-like endoplasmic reticulum (PERK) signaling mediated proapoptotic signals Middle East respiratory syndrome (MERS-CoV) infection, which converged intrinsic pathway. Inhibiting PERK or both alleviated MERS vivo. Severe acute...
SARS-CoV-2 has been confirmed in over 450 million cases since 2019. Although several vaccines have certified by the WHO and people are being vaccinated on a global scale, it reported that multiple variants can escape neutralization antibodies, resulting vaccine breakthrough infections. Bacillus Calmette-Guérin (BCG) is known to induce heterologous protection based trained immune responses. Here, we investigated whether BCG-induced immunity protected against K18-hACE2 mouse model. Our data...
Older individuals are at higher risk of SARS-CoV-2 infection and severe outcomes, but the underlying mechanisms incompletely understood. In addition, how age modulates re-infection vaccine breakthrough infections remain largely unexplored. Here, we investigated age-associated pathogenesis, immune responses, occurrence utilizing a wild-type C57BL/6N mouse model. We demonstrated that interferon adaptive antibody response upon challenge significantly impaired in aged mice compared to young...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 was a dominant circulating SARS-CoV-2 variant worldwide. Recent reports hint that is similarly potent regarding antibody evasion but may be more transmissible than BA.1. The pathogenicity of remains unclear and critical public health significance. Here we investigated the virological features with in vitro vivo models. We show less dependent on transmembrane protease serine (TMPRSS2) for virus entry comparison BA.1...
Among the Omicron sublineages that have emerged, BA.1, BA.2, BA.5, and their related resulted in largest number of infections. While recent studies demonstrated all robustly escape neutralizing antibody response, it remains unclear on whether these share any pattern evolutionary trajectory replication efficiency intrinsic pathogenicity along respiratory tract.We compared virological features, capacity dominant BA.2 BA.5 human nasal epithelium, characterized K18-hACE2, A129, young C57BL/6,...
Successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires proteolytic cleavage of the viral spike protein. While role host transmembrane protease serine in SARS-CoV-2 is widely recognized, involvement other proteases capable facilitating entry remains incompletely explored. Here, we show that multiple members from membrane-type matrix metalloproteinase (MT-MMP) and a disintegrin families can mediate entry. Inhibition MT-MMPs significantly reduces replication...
The overall success of worldwide mass vaccination in limiting the negative effect COVID-19 pandemics is inevitable, however, recent SARS-CoV-2 variants concern, especially Omicron and its sub-lineages, efficiently evade humoral immunity mounted upon or previous infection. Thus, it an important question whether these variants, vaccines against them, induce anti-viral cellular immunity. Here we show that mRNA vaccine BNT162b2 induces robust protective K18-hACE2 transgenic B-cell deficient...
SARS-CoV-2 JN.1 with an additional L455S mutation on spike when compared its parental variant BA.2.86 has outcompeted all earlier variants to become the dominant circulating variant. Recent studies investigated immune resistance of but factors are speculated contribute global dominance, which remain elusive until today. Here, we find that a higher infectivity than in differentiated primary human nasal epithelial cells (hNECs). Mechanistically, demonstrate gained over associates increased...
Circular RNAs (circRNAs) are an integral component of the host competitive endogenous RNA (ceRNA) network. These noncoding characterized by their unique splicing reactions to form covalently closed loop structures and play important regulatory roles in cells. Recent studies showed that circRNA expressions were perturbed viral infections circRNAs might serve as potential antiviral targets. We investigated ceRNA network changes biological relevance human lung adenocarcinoma epithelial (Calu-3)...
Rapid accumulation of viral proteins in host cells render viruses highly dependent on cellular chaperones including heat shock protein 90 (Hsp90). Three pathogenic human coronaviruses, MERS-CoV, SARS-CoV and SARS-CoV-2, have emerged the past 2 decades. However, there is no approved antiviral agent against these coronaviruses. We inspected role Hsp90 for coronavirus propagation. First, an inhibitor, 17-AAG, significantly suppressed MERS-CoV propagation cell lines physiological-relevant...
Besides prominent respiratory involvement, gastrointestinal manifestations are commonly reported in Coronavirus Disease 2019 (COVID-19) patients. We compared infection of ex vivo human intestinal tissues by SARS-CoV-2 and SARS-CoV with respect to their replication kinetics immune activation profile.Human were obtained from patients while undergoing surgical operations at Queen Mary Hospital, Hong Kong. Upon removal, the immediately processed infected or SARS-CoV. Replication determined...
"Pan-coronavirus" antivirals targeting conserved viral components can be designed. Here, we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high mannose found on proteins but seldom healthy human cells, potently inhibits Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute 2 (SARS-CoV-2) (including Omicron), and other human-pathogenic coronaviruses at nanomolar concentrations. H84T-BanLec protects against MERS-CoV...