- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- Infection Control and Ventilation
- Advanced Biosensing Techniques and Applications
- Thermal Regulation in Medicine
- Bacillus and Francisella bacterial research
- Nanoplatforms for cancer theranostics
- HIV Research and Treatment
- Immune responses and vaccinations
- Animal health and immunology
- Biosensors and Analytical Detection
- vaccines and immunoinformatics approaches
- Heparin-Induced Thrombocytopenia and Thrombosis
- Influenza Virus Research Studies
- COVID-19 and healthcare impacts
- Surgical site infection prevention
- Ubiquitin and proteasome pathways
- COVID-19 Impact on Reproduction
- Long-Term Effects of COVID-19
- Cytomegalovirus and herpesvirus research
- Respiratory viral infections research
University of Iowa
2020-2025
Rutgers, The State University of New Jersey
2024
Rutgers Sexual and Reproductive Health and Rights
2024
The recent emergence of B.1.1.529, the Omicron variant
Abstract Despite the development and deployment of antibody vaccine countermeasures, rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in spike protein jeopardize their efficacy. The recent emergence B.1.1.529, Omicron variant1,2, which has more than 30 protein, raised concerns for escape from protection by vaccines therapeutic antibodies. A test potential countermeasures against B.1.1.529 is activity pre-clinical rodent models respiratory tract disease. Here, using...
The SARS-CoV-2 Omicron subvariants BA.1 and BA.2 exhibit reduced lung cell infection relative to previously circulating variants, which may account for their pathogenicity. However, it is unclear whether by BA.5, displaced these remains attenuated. Here, we show that the spike (S) protein of BA.5 exhibits increased cleavage at S1/S2 site drives cell-cell fusion entry with higher efficiency than its counterparts from BA.2. Increased depends on mutation H69Δ/V70Δ associated efficient...
Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding spike protein. In contrast, whether antigenic occurs S2 remains largely elusive. Here, we perform a deep mutational scanning experiment to identify that affect three apex public antibodies. Our results indicate spatially diverse mutations, including D950N Q954H, which are observed Delta Omicron variants, respectively, weaken these Although antibodies known be nonneutralizing, show...
Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a series of single-domain antibodies (i.e., nanobody),
Abstract The fusion peptide of SARS-CoV-2 spike protein is functionally important for membrane during virus entry and part a broadly neutralizing epitope. However, sequence determinants at the its adjacent regions pathogenicity antigenicity remain elusive. In this study, we perform series deep mutational scanning (DMS) experiments on an S2 region spanning authentic in different cell lines presence antibodies. We identify mutations residue 813 that reduced TMPRSS2-mediated with decreased...
Several SARS-CoV-2 variants have shown increased transmissibility, calling for a need to develop effective vaccines with broadly neutralizing activity against multiple variants. This study identified non-neutralizing epitope on the receptor-binding domain (RBD) of spike protein, and further shielded it glycan probe.
With the recent approval of COVID-19 vaccines, recovered subjects who are vaccinated may be ideal candidates to donate convalescent plasma (CCP).
SARS-CoV-2 spike–based vaccines are used to control the COVID-19 pandemic. However, emerging variants have become resistant antibody neutralization and further mutations may lead full resistance. We tested whether T cells alone could provide protection without antibodies. designed a cell–based vaccine in which spike sequences were rearranged attached ubiquitin. Immunization of mice with induced no specific antibodies, but strong cell responses. challenged wild-type strain or an Omicron...
Background. The pathogenic coronaviruses (CoVs) MERS-CoV and SARS-CoV-2, which are responsible for the MERS outbreak COVID-19 pandemic, respectively, continue to infect humans, with significant adverse outcomes. There is a continuing need develop mucosal vaccines against these respiratory viral pathogens prevent entry replication at sites. receptor-binding domain (RBD) of CoV spike (S) protein critical vaccine target, glycan masking unique approach designing subunit improved neutralizing...
Coronaviruses express a repertoire of accessory proteins for evading host immune responses. A small internal (I) protein is expressed by the genus Betacoronavirus. Previous studies reported that I SARS-CoV, MERS-CoV and SARS-CoV-2 inhibit type interferon (IFN-I) expression through distinct mechanisms have different roles in pathogenesis. Human coronaviruses (hCoV) HKU1 OC43 are betacoronaviruses also encode as an protein. Although hCoV-HKU1 hCoV-OC43 predominantly cause common cold healthy...
Multiple SARS-CoV-2 variants are identified with higher rates of transmissibility or greater disease severity. Particularly, recent emergence Omicron variant rapid human-to-human transmission posts new challenges to the current prevention strategies. In this study, following vaccination an mRNA vaccine encoding receptor-binding domain (RBD-mRNA), we detected serum antibodies that neutralized pseudoviruses expressing spike (S) protein harboring single multiple mutations, as well authentic...
Safe, passive immunization methods are required against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants. Immunization of chickens with antigen is known to induce specific IgY antibodies concentrated in the egg yolk has a good safety profile, high yield per egg, can be topically applied, not requiring parenteral delivery. Our data provide first evidence prophylactic efficacy Immunoglobulin Y SARS-CoV-2 mice. Lohmann hens were injected recombinant RBD protein;...
Abstract Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a novel series of single-domain antibodies (i.e., nanobody), Nanosota-1, from camelid nanobody phage display library. Structural data showed that Nanosota-1 bound to oft-hidden receptor-binding domain (RBD) SARS-CoV-2 spike protein, blocking out viral receptor ACE2. The lead drug possessing an Fc tag ( Nanosota-1C-Fc ) RBD with K d 15.7picomolar (∼3000 times more tightly than ACE2 did) inhibited...
SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. We identified the host E3-ubiquitin ligase TRIM7 as an inhibitor apoptosis replication via ubiquitination membrane (M) protein.
Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, belonging to the genus beta-CoV, have caused outbreaks or pandemics. SARS-CoV-2 has evolved into many variants with increased resistance current vaccines. Spike (S) protein its receptor-binding domain (RBD) fragment of these CoVs are important vaccine targets; however, RBD Omicron variant is mutated, rending neutralizing antibodies elicited by ancestral-based vaccines targeting this region ineffective,...
The function of betacoronavirus internal protein has been relatively understudied. earliest report on the mouse hepatitis virus suggested that is a structural without significant functions in replication and virulence. However, proteins
encode a conserved accessory gene within the +1 open reading frame (ORF) of nucleocapsid called internal N gene. This is referred to as "I" for mouse hepatitis virus (MHV), ORF9b severe acute respiratory CoV (SARS-CoV) and SARS-CoV-2, ORF8b Middle East syndrome (MERS-CoV). Previous studies have shown immunoevasive properties, while only known information MHV I its localization virion hepatotropic/neurotropic A59 strain MHV. Whether an innate immune antagonist or has other functions not been...
SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. Here we show the host E3-ubiquitin ligase TRIM7 acts as an inhibitor apoptosis replication via ubiquitination membrane (M) protein. Trim7-/- mice exhibit increased pathology titers associated with epithelial dysregulated immune responses. Mechanistically, ubiquitinates M on K14, which protects cells...
Respiratory infections are a major health burden worldwide. syncytial virus (RSV) is among the leading causes of hospitalization in both young children and older adults. The onset severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic public response had profound impact on normal seasonal outbreaks other viruses. However, little known about how prior infection impacts SARS-CoV-2 disease outcomes. In this study, we examine previous RSV severity subsequent challenge BALB/c mice....
Widespread vaccination and natural infection have resulted in greatly decreased rates of severe disease, hospitalization death after subsequent or reinfection with SARS-CoV-2. New vaccine formulations are based on circulating strains virus, which tended to evolve more readily transmit human evade the neutralizing antibody response. An assumption this approach is that ancestral virus will not recur. Recurrence these could be a problem for individuals previously exposed spike protein by...
ABSTRACT The fusion peptide of SARS-CoV-2 spike protein is functionally important for membrane during virus entry and part a broadly neutralizing epitope. However, sequence determinants at the its adjacent regions pathogenicity antigenicity remain elusive. In this study, we performed series deep mutational scanning (DMS) experiments on an S2 region spanning authentic in different cell lines presence antibodies. We identified mutations residue 813 that reduced TMPRSS2-mediated with decreased...