Biology subjects

Ji, F.

Publications and source records attributed to Ji, F..

40 records · Page 3Linked to original sources

bioRxiv2020

Mass spectrometry analysis of newly emerging coronavirus HCoV-19 spike S protein and human ACE2 reveals camouflaging glycans and unique post-translational modifications

The pneumonia-causing COVID-19 pandemia has prompt worldwide efforts to understand its biological and clinical traits of newly identified HCoV-19 virus. In this study, post-translational modification (PTM) of recombinant HCoV-19 S and hACE2 were characterized by LC-MSMS. We revealed that both proteins were highly decorated with specific proportions of N-glycan subtypes. Out of 21 possible glycosites in HCoV-19 S protein, 20 were confirmed completely occupied by N-glycans, with oligomannose glycans being the most abundant type. All 7 possible glycosylation sites in hACE2 were completely occupied mainly by complex type N-glycans. However, we showed that glycosylation did not directly contribute to the binding affinity between SARS-CoV spike protein and hACE2. Additionally, we also identified multiple sites methylated in both proteins, and multiple prolines in hACE2 were converted to hydroxylproline. Refined structural models were built by adding N-glycan and PTMs to recently published cryo-EM structure of the HCoV-19 S and hACE2 generated with glycosylation sites in the vicinity of binding surface. The PTM and glycan maps of both HCoV-19 S and hACE2 provide additional structural details to study mechanisms underlying host attachment, immune response mediated by S protein and hACE2, as well as knowledge to develop remedies and vaccines desperately needed nowadays.

molecular biology↗

bioRxiv2020

Functional and Genetic Analysis of Viral Receptor ACE2 Orthologs Reveals Broad Potential Host Range of SARS-CoV-2

The pandemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health threat. Epidemiological studies suggest that bats are the natural zoonotic reservoir for SARS-CoV-2. However, the host range of SARS-CoV-2 and intermediate hosts that facilitate its transmission to humans remain unknown. The interaction of coronavirus with its host receptor is a key genetic determinant of host range and cross-species transmission. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as the receptor to enter host cells in a species-dependent manner. It has been shown that human, palm civet, pig and bat ACE2 can support virus entry, while the murine ortholog cannot. In this study, we characterized the ability of ACE2 from diverse species to support viral entry. We found that ACE2 is expressed in a wide range of species, with especially high conservation in mammals. By analyzing amino acid residues of ACE2 critical for virus entry, based on structure of SARS-CoV spike protein interaction with human, bat, palm civet, pig and ferret ACE2, we identified approximately eighty ACE2 proteins from mammals that could potentially mediate SARS-CoV-2 entry. We chose 48 representative ACE2 orthologs among eighty orthologs for functional analysis and it showed that 44 of these mammalian ACE2 orthologs, including those of domestic animals, pets, livestock, and animals commonly found in zoos and aquaria, could bind SARS-CoV-2 spike protein and support viral entry. In contrast, New World monkey ACE2 orthologs could not bind SARS-CoV-2 spike protein and support viral entry. We further identified the genetic determinant of New World monkey ACE2 that restricts viral entry using genetic and functional analyses. In summary, our study demonstrates that ACE2 from a remarkably broad range of species can facilitate SARS-CoV-2 entry. These findings highlight a potentially broad host tropism of SARS-CoV-2 and suggest that SARS-CoV-2 might be distributed much more widely than previously recognized, underscoring the necessity to monitor susceptible hosts to prevent future outbreaks.

microbiology↗

bioRxiv2018

Antimicrobial Activity of Tetrabromobisphenol A (TBBPA) against Staphylococcus aureus Skin Infections

Tetrabromobisphenol A (TBBPA) is a brominated flame retardant with selective antimicrobial activity against Gram-positive bacteria. We show that TBBPA exerts bactericidal effects by damaging the cell wall and membrane of Staphylococcus aureus (SA) without inducing antimicrobial resistance. In vivo skin infection assays indicate that a low dose of TBBPA could contribute to wound closure and attenuate SA infection and inflammatory infiltration. TBBPA has potential for use as an antimicrobial agent against Gram-positive pathogens.

microbiology↗

bioRxiv2018

Quality control-based signal drift correction and interpretations of metabolomics/proteomics data using random forest regression

Large-scale mass spectrometry-based metabolomics and proteomics study requires the long-term analysis of multiple batches of biological samples, which often accompanied with significant signal drift and various inter- and intra- batch variations. The unwanted variations can lead to poor inter- and intra-day reproducibility, which is a hindrance to discover real significance. We developed a novel quality control-based random forest signal correction algorithm, being ensemble learning approach to remove inter- and intra- batches of unwanted variations at feature-level. Our evaluation based on real samples showed the developed algorithm improved the data precision and statistical accuracy for metabolomics and proteomics, which was superior to other common correction methods. We have been able to improve its performance for interpretations of large-scale metabolomics and proteomics data, and to allow the improvement of the data precision for uncovering the real biologically differences.

bioinformatics↗