Publications by authors named "Zanxian Xia"

Article Synopsis
  • - The study investigates the genetic diversity and evolutionary dynamics of the Omicron variant of COVID-19 in Pakistan, analyzing 954 sequenced genomes during the fifth wave of the pandemic.
  • - Results show that the Pakistani Omicron variant originated from two distinct lineages and has low genetic diversity but significant mutations in the spike protein, with a notable increase in the population size at the end of 2021.
  • - The findings highlight Omicron's unique evolutionary path and the importance of global cooperation to monitor virus variants and improve pandemic response strategies.
View Article and Find Full Text PDF

Iminosugars, a class of polyhydroxylated cyclic alkaloids with intriguing properties, hold promising therapeutic potentials against a broad spectrum of enveloped viruses, including DENV, HCV, HIV, and influenza viruses. Mechanistically, iminosugars act as the competitive inhibitors of host endoplasmic reticular α-glucosidases I and II to  disrupt the proper folding of viral nascent glycoproteins, which thereby exerts antiviral effects. Remarkably, the glycoproteins of many enveloped viruses are significantly more dependent on the calnexin pathway of the protein folding than most host glycoproteins.

View Article and Find Full Text PDF
Article Synopsis
  • - The envelope (E) protein of SARS-CoV-2 is crucial for viral particle formation, ion channel function, and can induce harmful cellular responses like cell death and inflammation.
  • - Research identifies ubiquitin-specific protease 33 (USP33) as a factor that stabilizes E proteins, thus promoting viral replication; without USP33, E proteins degrade quickly, leading to lower virus levels and reduced inflammation.
  • - A new delivery method using lipid nanoparticles (LNP) to target and suppress USP33 has been shown to effectively inhibit viral replication in mouse lungs, providing a potential strategy for treating SARS-CoV-2 without causing long-term issues.
View Article and Find Full Text PDF

Extracellular vesicles (EVs) have emerged as key intercellular communication and pathogenesis mediators. Parasitic organisms' helminths, cause widespread infections with significant health impacts worldwide. Recent research has shed light on the role of EVs in the lifecycle, immune evasion, and disease progression of these parasitic organisms.

View Article and Find Full Text PDF
Article Synopsis
  • The ORF9b protein from SARS-CoV and SARS-CoV-2 is important for the virus to evade the immune system, but the specific ways it works are not fully understood.
  • This study shows that ORF9b can be tagged for degradation through a pathway involving ubiquitination and a complex formation with TOM70, HSP90α, and CUL5, where CUL5 helps degrade ORF9b while HSP90α stabilizes it.
  • Treatments that inhibit HSP90, such as GA or 17-AAG, increase the breakdown of ORF9b and reduce SARS-CoV-2 replication, indicating a potential target for new COVID-19 treatments and enhancing understanding of the host-virus
View Article and Find Full Text PDF

The progressive emergence of SARS-CoV-2 variants has necessitated the urgent exploration of novel therapeutic strategies to combat the COVID-19 pandemic. The SARS-CoV-2 main protease (M) represents an evolutionarily conserved therapeutic target for drug discovery. This study highlights the discovery of meisoindigo (Mei), derived from the traditional Chinese medicine (TCM) Indigo naturalis, as a novel non-covalent and nonpeptidic M inhibitor.

View Article and Find Full Text PDF

Meisoindigo (Mei) has long been recognized in chronic myeloid leukemia (CML) treatment. To elucidate its molecular target and mechanisms, we embarked on designing and synthesizing a series of Mei-derived PROTACs. Through this endeavor, VHL-type PROTAC was identified to be highly cytotoxic against SW620, SW480, and K562 cells.

View Article and Find Full Text PDF

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously producing new variants, necessitating effective therapeutics. Patients are not only confronted by the immediate symptoms of infection but also by the long-term health issues linked to long COVID-19. Activation of epidermal growth factor receptor (EGFR) signalling during SARS-CoV-2 infection promotes virus propagation, mucus hyperproduction, and pulmonary fibrosis, and suppresses the host's antiviral response.

View Article and Find Full Text PDF

M2-like polarized tumor-associated macrophages (TAMs) are the major component of infiltrating immune cells in hepatocellular carcinoma (HCC), which have been proved to exhibit significant immunosuppressive and pro-tumoral effects. However, the underlying mechanism of the tumor microenvironment (TME) educating TAMs to express M2-like phenotypes is still not fully understood. Here, we report that HCC-derived exosomes are involved in intercellular communications and exhibit a greater capacity to mediate TAMs' phenotypic differentiation.

View Article and Find Full Text PDF
Article Synopsis
  • Three human coronaviruses have emerged over the last two decades—SARS-CoV, MERS-CoV, and SARS-CoV-2—creating significant health and economic challenges that drive research into their characteristics and treatments.
  • MERS-CoV's ORF4b protein can suppress the immune response but is unstable and degraded by the host's ubiquitin proteasome system, specifically regulated by the UBR5 protein.
  • UBR5 diminishes ORF4b’s anti-immunity effects, thereby inhibiting MERS-CoV's ability to evade the immune system, showcasing a new mechanism through which host cells combat this virus.
View Article and Find Full Text PDF
Article Synopsis
  • Emerging evidence indicates that circular RNAs (circRNAs), particularly circMDK, play a significant role in the progression of hepatocellular carcinoma (HCC) and may serve as oncogenic markers.
  • CircMDK, found to be upregulated in HCC, enhances tumor growth and metastasis by sponging specific microRNAs and activating the PI3K/AKT/mTOR signaling pathway.
  • Delivery of circMDK-targeting siRNA using poly (β-amino esters) significantly inhibits HCC tumor progression in various mouse models, suggesting potential for nanotherapeutic applications in cancer treatment.
View Article and Find Full Text PDF

Motivation: Viruses continue to threaten human health. Yet, the complete viral species carried by humans and their infection characteristics have not been fully revealed.

Results: This study curated an atlas of human viruses from public databases and literature, and built the Human Virus Database (HVD).

View Article and Find Full Text PDF
Article Synopsis
  • - The novel coronavirus (SARS-CoV-2) has caused a global pandemic with over 23 million cases and at least 800,000 deaths as of August 2020, challenging healthcare systems worldwide.
  • - This review explores the characteristics of SARS-CoV-2, discusses potential treatments, and highlights technologies like CRISPR-Cas9 and PROteolysis TArgeting Chimeras for drug development and disease detection.
  • - Additionally, it covers the limited epidemiological data on COVID-19, ongoing vaccine efforts, and suggests future research directions to better understand the disease's molecular mechanisms.
View Article and Find Full Text PDF

The Wnt/β-catenin signaling pathway has been implicated as the central mechanism that drives colorectal carcinogenesis. Its activation is historically due to mutation on APC (adenomatous polyposis coli), resulting to nuclear localization of β-catenin and expression of Wnt target genes that promote tumor progression. Although this pathway seems to be a pivotal therapeutic target because of its critical role in colorectal cancer, there has been no clinically approved therapies targeting Wnt/β-catenin signaling pathway to this date.

View Article and Find Full Text PDF

With the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), coronaviruses have begun to attract great attention across the world. Of the known human coronaviruses, however, Middle East respiratory syndrome coronavirus (MERS-CoV) is the most lethal. Coronavirus proteins can be divided into three groups: nonstructural proteins, structural proteins, and accessory proteins.

View Article and Find Full Text PDF
Article Synopsis
  • In a study of 47 COVID-19 patients compared to 19 healthy controls, researchers found unique microorganisms in the COVID-19 group and significant changes in gut microbiota composition, including decreased butyrate producers and increased probiotic levels.
  • The research identified 15 microbial markers that could help diagnose COVID-19 and noted correlations between certain gut bacteria and clinical features of the disease, suggesting that gut microbiota alterations may impact COVID-19 severity.
View Article and Find Full Text PDF

Retinoic acid-inducible gene I (RIG-I) is a sensor that recognizes cytosolic double-stranded RNA derived from microbes to induce host immune response. Viruses, such as herpesviruses, deploy diverse mechanisms to derail RIG-I-dependent innate immune defense. In this study, we discovered that mouse RIG-I is intrinsically resistant to deamidation and evasion by herpes simplex virus 1 (HSV-1).

View Article and Find Full Text PDF

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly throughout the world. Although COVID-19 has a relatively low case severity rate compared to SARS and Middle East Respiratory syndrome it is a major public concern because of its rapid spread and devastating impact on the global economy. Scientists and clinicians are urgently trying to identify drugs to combat the virus with hundreds of clinical trials underway.

View Article and Find Full Text PDF

SARS-CoV-2 is the etiological agent responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). The main protease of SARS-CoV-2, 3CLpro, is an attractive target for antiviral inhibitors due to its indispensable role in viral replication and gene expression of viral proteins. The search of compounds that can effectively inhibit the crucial activity of 3CLpro, which results to interference of the virus life cycle, is now widely pursued.

View Article and Find Full Text PDF

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a widespread outbreak of highly pathogenic coronavirus disease 2019 (COVID-19). It is therefore important and timely to characterize interactions between the virus and host cell at the molecular level to understand its disease pathogenesis. To gain insights, we performed high-throughput sequencing that generated time-series data simultaneously for bioinformatics analysis of virus genomes and host transcriptomes implicated in SARS-CoV-2 infection.

View Article and Find Full Text PDF

Background: High incidence of venous thromboembolic complications in coronavirus disease 2019 (COVID-19) patients was noted recently.

Objective: This study aimed to explore the factors associated with prevalence of venous thromboembolism (VTE) in COVID-19 patients.

Methods: A literature search was conducted in several online databases.

View Article and Find Full Text PDF

This study aimed to provide systematic evidence for the association between multiorgan dysfunction and COVID-19 development. Several online databases were searched for articles published until May 13, 2020. Two investigators independently selected trials, extracted data, and evaluated the quality of individual trials.

View Article and Find Full Text PDF

Zika Virus (ZIKV) is a Flavivirus transmitted primarily via the bite of infected Aedes aegypti mosquitoes. Globally, 87 countries and territories have recorded autochthonous mosquito-borne transmission of ZIKV as at July 2019 and distributed across four of the six WHO Regions. Outbreaks of ZIKV infection peaked in 2016 and declined substantially throughout 2017 and 2018 in the Americas region.

View Article and Find Full Text PDF
Article Synopsis
  • A detailed study of the 2019-nCoV genome has shown notable differences from SARS and other similar coronaviruses.
  • Researchers found 380 specific amino acid changes that distinguish 2019-nCoV from these related viruses.
  • These differences may have led to unique functional and disease-causing characteristics in 2019-nCoV.
View Article and Find Full Text PDF