A5087524000- interferon and immune responses
- Viral Infections and Vectors
- Biochemical and Molecular Research
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- Hepatitis C virus research
- HIV/AIDS drug development and treatment
- Computational Drug Discovery Methods
- Immune Response and Inflammation
- Malaria Research and Control
- Animal Virus Infections Studies
- Tuberculosis Research and Epidemiology
- Immune Cell Function and Interaction
- Influenza Virus Research Studies
- Inflammasome and immune disorders
- Toxoplasma gondii Research Studies
- Viral gastroenteritis research and epidemiology
- Endoplasmic Reticulum Stress and Disease
- Receptor Mechanisms and Signaling
- Infectious Encephalopathies and Encephalitis
- Cancer therapeutics and mechanisms
- Innovation and Socioeconomic Development
- Vector-borne infectious diseases
- Animal Disease Management and Epidemiology
The University of Texas Southwestern Medical Center
2018-2024
University of Utah
2022-2024
Howard Hughes Medical Institute
2021-2024
Children's Medical Center
2021
Ahram Canadian University
2021
Interferons (IFNs) contribute to cell-intrinsic antiviral immunity by inducing hundreds of interferon-stimulated genes (ISGs). In a screen identify ISGs, we unexpectedly found that LY6E, member the LY6/uPAR family, enhanced viral infection. Here, show enhancement ectopically expressed LY6E extends several cellular backgrounds and affects multiple RNA viruses. does not impair IFN activity or signaling, but rather promotes entry. Using influenza A virus as model, narrow enhancing effect...
Viruses acquire host genes via horizontal transfer and can express them to manipulate biology during infections. Some homologs retain sequence identity, but evolutionary divergence obscure origins. We use structural modeling compare vaccinia virus proteins with metazoan proteomes. identify A47L as a homolog of gasdermins, the executioners pyroptosis. An X-ray crystal structure A47 confirms this homology, cell-based assays reveal that interferes caspase function. also C1L product cryptic gene...
Significance Flaviviruses are significant human pathogens and emerging infectious disease threats. A screen of interferon-inducible genes revealed Shiftless (SHFL) as a potent antiviral effector, inhibiting all Flaviviridae tested, including West Nile, Zika, dengue, yellow fever, hepatitis C viruses. Mechanistic studies showed that SHFL inhibits viral replication at point after translation the incoming genome. In whole-body Shfl knockout (KO) mice, compared to wild-type KO mice were more...
Abstract Zika and dengue virus nonstructural protein 5 antagonism of STAT2, a critical interferon signaling transcription factor, to suppress the host response is required for viremia pathogenesis in vertebrate host. This affects viral species tropism, as mouse STAT2 resistance renders only immunocompromised or humanized mice infectable. Here, we explore how evolution impacts antagonism. By measuring susceptibility 38 diverse proteins, demonstrate that arose numerous times mammalian...
The continuing heavy toll of the COVID-19 pandemic necessitates development therapeutic options. We adopted structure-based drug repurposing to screen FDA-approved drugs for inhibitory effects against main protease enzyme (Mpro) substrate-binding pocket SARS-CoV-2 non-covalent and covalent binding. Top candidates were screened infectious in a cell-based viral replication assay. Promising included atovaquone, mebendazole, ouabain, dronedarone, entacapone, although atovaquone mebendazole only...
Mammalian mRNAs possess an N7-methylguanosine (m7G) cap and 2’O methylation of the initiating nucleotide at their 5’ end, whereas certain viral RNAs lack these characteristic features. The human antiviral restriction factor IFIT1 recognizes binds to specific that features host mRNAs, resulting in targeted suppression RNA translation. This interaction imposes significant host-driven evolutionary pressures on viruses, many viruses have evolved mechanisms evade action IFIT1. However, little is...
<p>The newly emerged coronavirus, SARS-CoV-2, and the resulting COVID-19 disease, has spread swiftly across globe since its initial detection in December 2019. Given heavy toll of this pandemic, therapeutic options for treatment are urgently needed. Here, we adopted a repositioning approach using in-silico molecular modeling to screen FDA-approved drugs with established safety profiles potential inhibitory effects against SARS-CoV-2. We used structure-based drug design more than 2000...
The rapid evolution of SARS-CoV-2 variants highlights the need for new therapies to prevent disease spread. SARS-CoV-2, like SARS-CoV-1, uses human cell surface protein angiotensin-converting enzyme 2 (ACE2) as its native receptor. Here, we design and characterize a mutant ACE2 that enables affinity purification dimeric by altering active site autoproteolytic digestion C-terminal His
The newly emerged coronavirus, SARS-CoV-2, and the resulting COVID-19 disease, has spread swiftly across globe since its initial detection in December 2019. Given heavy toll of this pandemic, therapeutic options for treatment are urgently needed. Here, we adopted a repositioning approach using in-silico molecular modeling to screen FDA-approved drugs with established safety profiles potential inhibitory effects against SARS-CoV-2. We used structure-based drug design more than 2000 FDA...
Given the continuing heavy toll of COVID-19 pandemic, therapeutic options for treatment are urgently needed. Here, we adopted a repositioning approach using in silico molecular modeling to screen FDA-approved drugs with established safety profiles potential inhibitory effects against SARS-CoV-2. We used structure-based drug design more than 2000 FDA approved SARS-CoV-2 main protease enzyme (Mpro) substrate-binding pocket. additionally screened top hits from both sites covalent binding via...
Viruses acquire host genes via horizontal gene transfer and can express them to manipulate biology during infections. Some viral homologs retain sequence identity, but evolutionary divergence obscure origins. We used structural modeling compare vaccinia virus proteins with metazoan proteomes. identified
Given the continuing heavy toll of COVID-19 pandemic, therapeutic options for treatment are urgently needed. Here, we adopted a repositioning approach using in silico molecular modeling to screen FDA-approved drugs with established safety profiles potential inhibitory effects against SARS-CoV-2. We used structure-based drug design more than 2000 FDA approved SARS-CoV-2 main protease enzyme (Mpro) substrate-binding pocket. additionally screened top hits from both sites covalent binding via...
Mammalian mRNAs possess an N7-methylguanosine (m7G) cap and 2'O methylation of the initiating nucleotide at their 5' end, whereas certain viral RNAs lack these characteristic features. The human antiviral restriction factor IFIT1 recognizes binds to specific that features host mRNAs, resulting in targeted suppression RNA translation. This interaction imposes significant host-driven evolutionary pressures on viruses, many viruses have evolved mechanisms evade action IFIT1. However, little is...
Mammalian mRNAs possess an N7-methylguanosine (m7G) cap and 2’O methylation of the initiating nucleotide at their 5’ end, whereas certain viral RNAs lack these characteristic features. The human antiviral restriction factor IFIT1 recognizes binds to specific that features host mRNAs, resulting in targeted suppression RNA translation. This interaction imposes significant host-driven evolutionary pressures on viruses, many viruses have evolved mechanisms evade action IFIT1. However, little is...
Abstract The rapid evolution of SARS-CoV-2 variants highlights the need for new therapies to prevent disease spread. SARS-CoV-2, like SARS-CoV-1, uses human cell surface protein angiotensin-converting enzyme 2 (ACE2) as its native receptor. Here, we design and characterize a mutant ACE2 that enables affinity purification dimeric by altering active site autoproteolytic digestion C-terminal His 10 epitope tag. In cultured cells, competitively inhibits lentiviral vectors pseudotyped with spike...
The Receptor Transporter Protein (RTP) family is present in most, if not all jawed vertebrates. Most of our knowledge this protein comes from studies on mammalian RTPs, which are multi-function proteins that regulate cell-surface G-protein coupled receptor levels, influence olfactory system development, immune signaling, and directly inhibit viral infection. However, mammals comprise less than one-tenth extant vertebrate species, about the expression, function, evolution non-mammalian RTPs...
Given the continuing heavy toll of COVID-19 pandemic, therapeutic options for treatment are urgently needed. Here, we adopted a repositioning approach using in silico molecular modeling to screen FDA-approved drugs with established safety profiles potential inhibitory effects against SARS-CoV-2. We used structure-based drug design more than 2000 FDA approved SARS-CoV-2 main protease enzyme (Mpro) substrate-binding pocket. additionally screened top hits from both sites covalent binding via...
Given the continuing heavy toll of COVID-19 pandemic, therapeutic options for treatment are urgently needed. Here, we adopted a repositioning approach using in silico molecular modeling to screen FDA-approved drugs with established safety profiles potential inhibitory effects against SARS-CoV-2. We used structure-based drug design more than 2000 FDA approved SARS-CoV-2 main protease enzyme (Mpro) substrate-binding pocket. additionally screened top hits from both sites covalent binding via...