A5070703755- Virology and Viral Diseases
- Respiratory viral infections research
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- Influenza Virus Research Studies
- Viral Infections and Immunology Research
- COVID-19 Clinical Research Studies
- Viral Infections and Vectors
- HIV Research and Treatment
- Animal Virus Infections Studies
- vaccines and immunoinformatics approaches
- SARS-CoV-2 detection and testing
- Endoplasmic Reticulum Stress and Disease
- Bacteriophages and microbial interactions
- Mosquito-borne diseases and control
- Immune responses and vaccinations
- Gut microbiota and health
- Viral Infections and Outbreaks Research
- Parvovirus B19 Infection Studies
- Cellular transport and secretion
- Pneumonia and Respiratory Infections
- Ubiquitin and proteasome pathways
- Immunodeficiency and Autoimmune Disorders
- Computational Drug Discovery Methods
Georgia State University
2015-2024
Emory University
2009-2022
Friedrich-Loeffler-Institut
2022
Georgia Southern University
2020-2021
Keele University
2020
University of Minnesota Rochester
2020
St. Vincent's Birmingham
2020
Emmanuel College - Massachusetts
2020
RELX Group (Netherlands)
2020
Children's Healthcare of Atlanta
2009-2013
The coronavirus disease 2019 (COVID-19) pandemic is having a catastrophic impact on human health1. Widespread community transmission has triggered stringent distancing measures with severe socio-economic consequences. Gaining control of the will depend interruption chains until vaccine-induced or naturally acquired protective herd immunity arises. However, approved antiviral treatments such as remdesivir and reconvalescent serum cannot be delivered orally2,3, making them poorly suitable for...
A next-generation, broad-spectrum, orally efficacious influenza and B virus inhibitor is associated with a high genetic resistance barrier.
Morbidity and mortality resulting from influenza-like disease are a threat, especially for older adults. To improve case management, next-generation broad-spectrum antiviral therapeutics that efficacious against major drivers of disease, including influenza viruses respiratory syncytial virus (RSV), urgently needed.
Preparing antiviral defenses Antiviral drugs are an important tool in the battle against COVID-19. Both remdesivir and molnupiravir, which target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase, were first developed other RNA viruses. This highlights importance of broad-spectrum antivirals that can be rapidly deployed related emerging pathogens. Sourimant et al . used syncytial virus (RSV) as a primary indication identifying further polymerase enzyme The authors...
The yeast Ca 2+ adenosine triphosphatase Pmr1, located in medial-Golgi, has been implicated intracellular transport of and Mn ions. We show here that addition greatly alleviates defects ofpmr1 mutants N-linked O-linked protein glycosylation. In contrast, accurate sorting carboxypeptidase Y (CpY) to the vacuole requires a sufficient supply intralumenal . Most remarkably, pmr1 are also unable degrade CpY*, misfolded soluble endoplasmic reticulum protein, display phenotypes similar defective...
We have studied components of the endoplasmic reticulum (ER) proofreading and degradation system in yeast Saccharomyces cerevisiae. Using a der3–1 mutant defective mutated lumenal protein, carboxypeptidase yscY (CPY*), gene was cloned which encodes 64-kDa protein ER membrane. Der3p found to be identical with Hrd1p, identified necessary for HMG-CoA reductase. contains five putative transmembrane domains long hydrophilic C-terminal tail containing RING-H2 finger domain is oriented lumen....
Degradation of misfolded or tightly regulated proteins in the endoplasmic reticulum (ER) is performed by cytosolic ubiquitin-proteasome system and therefore requires their prior transport back to cytosol. Here, we report on extraction degradation mechanism a polytopic membrane protein. Rapid proteasomal mutated form ATP-binding cassette transporter Pdr5 retained ER initialized at lumenal face membrane. Using different antibodies directed against tails loop transmembrane protein, it could be...
Abstract Measles virus (MeV) remains a major human pathogen, but there are presently no licensed antivirals to treat MeV or other paramyxoviruses. Here, we use cryo-electron tomography (cryo-ET) elucidate the principles governing paramyxovirus assembly in MeV-infected cells. The three-dimensional (3D) arrangement of structural proteins including surface glycoproteins (F and H), matrix protein (M), ribonucleoprotein complex (RNP) characterized at stages budding, released particles. M is...
Abstract Remdesivir is an antiviral approved for COVID-19 treatment, but its wider use limited by intravenous delivery. An orally bioavailable remdesivir analog may boost therapeutic benefit facilitating early administration to non-hospitalized patients. This study characterizes the anti-SARS-CoV-2 efficacy of GS-621763, oral prodrug parent nucleoside GS-441524. Both GS-621763 and GS-441524 inhibit SARS-CoV-2, including variants concern (VOC) in cell culture human airway epithelium...
Abstract SARS-CoV-2 variants of concern (VOC) have triggered infection waves. Oral antivirals such as molnupiravir promise to improve disease management, but efficacy against VOC delta was questioned and potency omicron is unknown. This study evaluates in human airway epithelium organoids, ferrets, a lethal Roborovski dwarf hamster model severe COVID-19-like lung injury. were equally inhibited by cells organoids. Treatment reduced shedding ferrets prevented transmission. Pathogenicity...
The gut microbiome is intricately coupled with immune regulation and metabolism, but its role in Coronavirus Disease 2019 (COVID-19) not fully understood. Severe fatal COVID-19 characterized by poor anti-viral immunity hypercoagulation, particularly males. Here, we define multiple pathways which the protects mammalian hosts from SARS-CoV-2 intranasal infection, both locally systemically, via production of short-chain fatty acids (SCFAs). SCFAs reduced viral burdens airways intestines...
Abstract Therapeutic options against SARS-CoV-2 are underutilized. Two oral drugs, molnupiravir and paxlovid (nirmatrelvir/ritonavir), have received emergency use authorization. Initial trials suggested greater efficacy of paxlovid, but recent studies indicated comparable potency in older adults. Here, we compare both drugs two animal models; the Roborovski dwarf hamster model for severe COVID-19-like lung infection ferret transmission model. Dwarf hamsters treated with either drug survive...
ABSTRACT The endoplasmic reticulum contains a quality control system that subjects misfolded or unassembled secretory proteins to rapid degradation via the cytosolic ubiquitin proteasome system. This requires retrograde protein transport from back cytosol. Sec61 pore, central component of import channel into reticulum, was identified as core subunit retro-translocon well. As mutated lumen is successfully terminated, new targeting mechanism must exist mediates re-entering pore lumenal side de...
Paramyxovirinae envelope glycoproteins constitute a premier model to dissect how specific and dynamic interactions in multisubunit membrane protein complexes can control deep-seated conformational rearrangements. However, individual residues that determine reciprocal specificity of the viral attachment fusion (F) proteins have not been identified. We developed an assay based on pair canine distemper virus (CDV) F (strains Onderstepoort (ODP) Lederle) share ∼95% identity but differ their...
ABSTRACT Respiratory syncytial virus (RSV) is the leading cause of death due to a viral etiology in infants. RSV disease characterized by epithelial desquamation, neutrophilic bronchiolitis and pneumonia, obstructive pulmonary mucus. It has been shown that infection BALB/cJ mice with clinical isolate A2001/2-20 (2-20) results higher early load, greater airway necrosis, levels interleukin-13 (IL-13) mucin expression than laboratory strain A2. We hypothesized fusion (F) protein 2-20...