A5110648171- Viral Infections and Outbreaks Research
- Viral gastroenteritis research and epidemiology
- Hepatitis C virus research
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Vectors
- Hepatitis B Virus Studies
- Computational Drug Discovery Methods
- HIV Research and Treatment
- Bacteriophages and microbial interactions
- HIV/AIDS drug development and treatment
- Cytomegalovirus and herpesvirus research
- interferon and immune responses
- SARS-CoV-2 detection and testing
- T-cell and Retrovirus Studies
- Animal Disease Management and Epidemiology
- Influenza Virus Research Studies
- COVID-19 Clinical Research Studies
- Genomics and Chromatin Dynamics
- Flavonoids in Medical Research
- Phytochemistry and Biological Activities
- Infection Control and Ventilation
- Advanced Proteomics Techniques and Applications
- Pharmacological Effects of Natural Compounds
- Viral Infections and Immunology Research
- thermodynamics and calorimetric analyses
Emory University
2009-2024
Children's Healthcare of Atlanta
2021-2024
Cocrystal Pharma
2017
Princeton University
2012
University of Minnesota
2012
Augusta University
2008
Shanghai Medical College of Fudan University
2003-2005
National Natural Science Foundation of China
2003
Fudan University
2003
PSI-7977, a prodrug of 2'-F-2'-C-methyluridine monophosphate, is the purified diastereoisomer PSI-7851 and currently being investigated in phase 3 clinical trials for treatment hepatitis C. In this study, we profiled activity PSI-7977 its ability to select resistance using number different replicon cells. Results showed that was active against genotype (GT) 1a, 1b, 2a (strain JFH-1) replicons chimeric containing GT J6), 2b, 3a NS5B polymerase. Cross-resistance studies 1b confirmed S282T...
Coronavirus Disease 2019 (COVID-19) is a deadly emerging infectious disease caused by Severe Acute Respiratory Syndrome 2 (SARS-CoV-2). Because SARS-CoV-2 easily transmitted through the air and has relatively long incubation time, COVID-19 rapidly developed into global pandemic. As there are no antiviral agents for prevention treatment of this severe pathogen except remdesivir, development therapies to treat infected individuals remains highly urgent. Here, we showed that baicalein baicalin...
Abstract The early steps of HIV-1 infection, such as uncoating, reverse transcription, nuclear import, and transport to integration sites are incompletely understood. Here, we imaged entry replication complexes in cell lines, primary monocyte-derived macrophages (MDMs) CD4 + T cells. We show that viral traffic accumulate within speckles these precede the completion DNA synthesis. is dependent on interaction capsid proteins with host cleavage polyadenylation specificity factor 6 (CPSF6),...
Abstract The antiviral component of Paxlovid, nirmatrelvir (NIR), forms a covalent bond with Cys145 SARS-CoV-2 nsp5. To explore NIR resistance we designed mutations to impair binding over substrate. Using 12 Omicron (BA.1) and WA.1 replicons, cell-based complementation enzymatic assays, showed that in both strains, E166V imparted high (∼55-fold), major decrease WA1 replicon fitness (∼20-fold), but not BA.1 (∼2-fold). was restored by L50F. These differences may contribute potentially lower...
ABSTRACT Several arenaviruses can cause hemorrhagic fever diseases (VHFs) in humans, the pathogenic mechanism of which is poorly understood due to their virulent nature and lack molecular clones. A safe, convenient, economical small animal model arenavirus based on guinea pigs infected by Pichinde (PICV). PICV does not disease but an adapted strain (P18) causes a that mimics humans many aspects, while low-passaged (P2) remains avirulent animals. In order identify virulence determinants...
Arenaviruses cause severe hemorrhagic fever diseases in humans, and there are limited preventative therapeutic measures against these diseases. Previous structural functional analyses of arenavirus nucleoproteins (NPs) revealed a conserved DEDDH exoribonuclease (RNase) domain that is important for type I interferon (IFN) suppression, but the biological roles NP RNase viral replication host immune suppression have not been well characterized. Infection guinea pigs with Pichinde virus (PICV),...
The COVID-19 pandemic has emphasized the urgency for effective antiviral therapies against SARS-CoV-2. Targeting main protease (3CLpro) of virus emerged as a promising approach, and nirmatrelvir (PF-07321332), active component Pfizer's oral drug Paxlovid, demonstrated remarkable clinical efficacy. However, emergence resistance mutations poses challenge to its continued success. In this study, we employed alchemical free energy perturbation (FEP) alanine scanning identify...
Chronic infection by hepatitis C virus (HCV) is closely correlated with serious liver diseases. Although considerable progress has been made during recent years, the mechanism of replication and pathogenesis HCV are still elusive. We have applied proteomic techniques in this work to globally analyze protein expression profiles a human cell lines Huh7 absence presence replication, aiming at elucidating components cellular responses replication. The mixtures three subcellular fractions from...
Arenaviruses are enveloped single‐strand RNA viruses that mostly have natural hosts in rodents. Upon infection of humans, several arenaviruses can cause severe hemorrhagic fever diseases, including Lassa is endemic West Africa. The virulence mechanism these deadly be studied a safe and economical small animal model—guinea pigs infected by nonpathogenic arenavirus Pichinde virus (PICV), virulent strain which similar disease syndromes guinea as arenaviral fevers humans. We recently developed...
ABSTRACT Several arenaviruses are responsible for causing viral hemorrhagic fevers (VHF) in humans. Lassa virus (LASV), the causative agent of fever, is a biosafety level 4 (BSL4) pathogen that requires handling BSL4 facilities. In contrast, Pichinde arenavirus (PICV) BSL2 can cause fever-like symptoms guinea pigs resemble those observed human fever. Comparative sequence analysis avirulent P2 strain PICV and virulent P18 shows high degree homology bisegmented genome between two strains...
It has been suggested that cellular proteins are involved in hepatitis C virus (HCV) RNA replication. By using the yeast two‐hybrid system, we isolated seven cDNA clones encoding interacting with HCV polymerase (NS5B) from a human liver library. For one of these, α‐actinin, confirmed interaction by coimmunoprecipitation, immunofluorescent staining and confocal microscopic analysis. Experiments deletion mutants showed domains NS5B 84–95 , 466–478 α‐actinin 621–733 responsible for interaction....
RNA viruses are highly successful pathogens and the causative agents for many important diseases. To fully understand replication of these it is necessary to address roles both positive-strand ((+)RNA) negative-strand ((−)RNA), their interplay with viral host proteins. Here we used branched DNA (bDNA) fluorescence in situ hybridization (FISH) stain abundant (+)RNA far less (−)RNA hepatitis C virus (HCV)- Zika virus-infected cells, combined analyses visualization proteins through confocal...
Lassa virus (LASV) is a mammarenavirus (arenavirus) that causes zoonotic infection in humans can lead to fatal hemorrhagic fever (LF) disease. Currently, there are no FDA-approved vaccines or therapeutics against LASV. Development of treatments LF and other related arenavirus-induced fevers (AHFs) requires relevant animal models recapitulate clinical pathological features AHF diseases humans. Laboratory mice generally resistant LASV infection, non-human primates, while being good model for...
Arenaviruses, such as Lassa virus (LASV), can cause severe and fatal hemorrhagic fevers (e.g., fever, LF) in humans with no vaccines or therapeutics. Research on arenavirus-induced (AHFs) has been hampered by the highly virulent nature of these viral pathogens, which require high biocontainment laboratory, lack an immune-competent small animal model that recapitulate AHF disease pathological features. Guinea pig infected Pichinde (PICV), arenavirus does not humans, established a convenient...
Arenaviruses include several causative agents of haemorrhagic fever disease in humans. In addition, the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a superb model for study virus-host interactions, including basis viral persistence and associated diseases. There little understanding about molecular mechanisms concerning regulation specific role proteins modulating arenavirus-host cell interactions either with an acute or persistent infection, disease. Here, we report...
To establish an efficient, sensitive, cell-based assay system for NS3 serine protease in effort to study further the property of hepatitis C virus (HCV) and develop new antiviral agents.We constructed pCI-neo-NS3/4A-SEAP chimeric plasmid, which secreted alkaline phosphatase (SEAP) was fused in-frame downstream NS4A/4B cleavage site. The activity reflected by SEAP culture media transient or stable expression cells. Stably expressing cell lines were obtained G418 selection. Pefabloc SC, a...
ABSTRACT Replicon-based technologies were used to develop reagents and assays for advanced drug discovery efforts against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), examining all facets of the SARS-CoV-2 replication cycle at reduced biocontainment level. Specifically: a) 21 replicons cloned in bacterial artificial chromosomes (BACs) delivered as transfectable plasmid DNA or transcribed RNA various cell types. Replicons carrying mutations that affect activity antiviral...
Capturing the dynamic replication and assembly processes of viruses has been hindered by lack robust in situ hybridization (ISH) technologies that enable sensitive simultaneous labeling viral nucleic acid protein. Conventional DNA fluorescence (FISH) methods are often not compatible with immunostaining. We have therefore developed an imaging approach, MICDDRP (multiplex immunofluorescent cell-based detection DNA, RNA protein), which enables single-cell visualization RNA, Compared to...
Human coronaviruses are a continuous threat to the human population and have limited antiviral treatments, recent COVID-19 pandemic sparked interest in finding new strategies, such as natural products, combat emerging coronaviruses. Rapid efforts scientific community identify effective agents for remain focus minimize mortalities global setbacks. In this study, an essential oil derived from Myrtus communis L. (MEO) is against HCoV-229E HCoV-OC43 virus infections comparison two FDA-approved...