A5025975648- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- vaccines and immunoinformatics approaches
- interferon and immune responses
- Long-Term Effects of COVID-19
- Vector-borne infectious diseases
- Viral Infections and Vectors
- Antimicrobial Peptides and Activities
- Viral gastroenteritis research and epidemiology
- CAR-T cell therapy research
- Animal Virus Infections Studies
- Bacteriophages and microbial interactions
- S100 Proteins and Annexins
- CRISPR and Genetic Engineering
- Research on Leishmaniasis Studies
- Mosquito-borne diseases and control
- Protease and Inhibitor Mechanisms
- Extracellular vesicles in disease
- Venomous Animal Envenomation and Studies
- Immunotherapy and Immune Responses
- Traumatic Brain Injury and Neurovascular Disturbances
- Advanced Biosensing Techniques and Applications
The University of Texas Medical Branch at Galveston
2017-2025
Galveston College
2023
Medical University of Silesia
2014
Host-cell cysteine proteases play an essential role in the processing of viral spike protein SARS coronaviruses. K777, irreversible, covalent inactivator that has recently completed phase 1 clinical trials, reduced SARS-CoV-2 infectivity several host cells: Vero E6 (EC50< 74 nM), HeLa/ACE2 (4 Caco-2 (EC90 = 4.3 μM), and A549/ACE2 (<80 nM). Infectivity Calu-3 cells depended on cell line assayed. If Calu-3/2B4 was used, EC50 7 nM, but ATCC without ACE2 enrichment, >10 μM. There no toxicity to...
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2MPro ) to digest two of translated long polypeptides form a number mature proteins that are essential for viral replication and pathogenesis. Inhibition this vital proteolytic process is effective in preventing the virus from replicating infected cells therefore provides potential treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 (SC1MPro ), we have designed synthesized series SC2MPro inhibitors...
Guided by a computational docking analysis, about 30 Food and Drug Administration/European Medicines Agency (FDA/EMA)-approved small-molecule medicines were characterized on their inhibition of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). Of these small molecules tested, six displayed concentration that inhibits response 50% (IC50) value below 100 μM in inhibiting Mpro, and, importantly, three, is, pimozide, ebastine, bepridil, are basic potentiate...
Significance Effective therapies are urgently needed for COVID-19. We rapidly (within a week) identified fully human monoclonal germline-like antibody (ab1) from phage-displayed libraries that potently inhibited mouse ACE2-adapted SARS-CoV-2 replication in wild-type BALB/c mice and native virus transgenic expressing ACE2 as well hamsters when administered before challenge. It was also effective after infection of hamsters, although at lower efficacy than used prophylactically. Ab1 highly...
SARS-CoV-2 is a novel virus with many unknowns. No vaccine or specific therapy available yet to prevent and treat this deadly virus.
The key to battling the COVID-19 pandemic and its potential aftermath is develop a variety of vaccines that are efficacious safe, elicit lasting immunity, cover range SARS-CoV-2 variants. Recombinant viral receptor-binding domains (RBDs) safe vaccine candidates but often have limited efficacy due lack virus-like immunogen display pattern. Here we developed novel nanoparticle (VLP) displays 120 copies RBD on surface. This VLP-RBD mimics virus-based in display, which boosts efficacy, while...
Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and promising drug target novel antivirals against SARS-CoV-2. The marine natural product gallinamide A several synthetic analogues were identified as potent inhibitors of cathepsin with IC50 values in the picomolar range. Lead molecules possessed selectivity over other cathepsins alternative proteases involved viral entry. Gallinamide directly interacted cells and, together two lead analogues, potently...
A “universal” platform that can rapidly generate multiplex vaccine candidates is critically needed to control pandemics. Using the severe acute respiratory syndrome coronavirus 2 as a model, we have developed such by CRISPR engineering of bacteriophage T4. pipeline was engineered incorporating various viral components into appropriate compartments phage nanoparticle structure. These include expressible spike genes in genome, and envelope epitopes surface decorations, nucleocapsid proteins...
Inhibitors of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M pro ) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing severity COVID-19, but presence resistance-conferring mutations sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function against these mutants are thus urgently needed. We hypothesized covalent hepatitis C virus inhibitor boceprevir (BPV) could...
Effective therapies are urgently needed for COVID-19. Here we describe the identification of a new stable human immunoglobulin G1 heavy-chain variable (VH) domain scaffold that was used construction large library, lCAT6, engineered VHs. This library panned against receptor-binding (RBD) SARS-CoV-2 spike (S) glycoprotein. Two VH domains (VH ab6 and m397) were selected fused to Fc increased half-life in circulation. The VH-Fc m397 specifically neutralized with high potencies (50%...
According to the World Health Organization, COVID-19 may have caused ~15-million deaths across globe and is still ravaging world. Another wave of ~100 million infections predicted in United States due emergence highly transmissible immune-escaped Omicron variants.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance VOCs bring unprecedented challenges epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current has surprising tolerance mutations adjacent or within its interaction epitope. Cryo-electron microscopy structure showed 2G1 bound tip receptor binding domain (RBD) spike protein...
Thromboembolic complications and excessive inflammation are frequent in severe COVID-19, potentially leading to long COVID. In non-COVID studies, we others demonstrated that circulating Reelin promotes leukocyte infiltration thrombosis. Thus, hypothesized participates endothelial dysfunction hyperinflammation during COVID-19. We showed was increased COVID-19 patients correlated with the disease activity. group, observed a hyperinflammatory state, as judged by concentration of cytokines...
COVID-associated coagulopathy seemly plays a key role in post-acute sequelae of SARS- CoV-2 infection. However, the underlying pathophysiological mechanisms are poorly understood, largely due to lack suitable animal models that recapitulate clinical and pathological symptoms. Here, we fully characterized AC70 line human ACE2 transgenic (AC70 hACE2 Tg) mice for SARS-CoV-2 We noted this model is highly permissive with values 50% lethal dose infectious as ~ 3 0.5 TCID50 SARS-CoV-2,...
SARS-CoV-2 3CL protease (Main protease) and human cathepsin L are proteases that play unique roles in the infection of cells by SARS-CoV-2, causative agent COVID-19. Both recognize leucine other hydrophobic amino acids at P2 position a peptidomimetic inhibitor. At P1 position, accepts many acid side chains, with partial preference for phenylalanine, while 3CL-PR has stringent specificity glutamine or analogues. We have designed, synthesized, evaluated aldehyde dual-target (dual-acting)...
Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and -2 (SARS-CoV-2) are beta-coronaviruses (β-CoVs) that have caused significant morbidity mortality worldwide. Therefore, a better understanding of host responses to β-CoVs would provide insights into the pathogenesis these viruses identify potential targets for medical countermeasures. In this study, our objective is use systems biology approach explore magnitude scope innate immune triggered by SARS-CoV-1 infection over time in...
The rapid evolution of the viral genome has led to continual generation new variants SARS-CoV-2. Developing antibody drugs with broad-spectrum and high efficiency is a long-term task. It promising but challenging develop therapeutic neutralizing antibodies (nAbs) through in vitro based on antigen–antibody binding interactions. From an early B cell repertoire, we isolated 8G3 that retains its nonregressive activity against Omicron BA.1 various other strains vitro. protected ACE2 transgenic...
Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors all these proteases. However, the intrinsic, high electrophilicity aldehyde group is associated with safety concerns metabolic instability, limiting use drugs. We developed a novel self-masked (SMAIs) cruzain, major cysteine protease causative agent...
ABSTRACT Guided by a computational docking analysis, about 30 FDA/EMA-approved small molecule medicines were characterized on their inhibition of the SARS-CoV-2 main protease (M Pro ). Of these tested medicines, six displayed an IC 50 value in inhibiting M below 100 μM. Three pimozide, ebastine, and bepridil are basic molecules. Their uses COVID-19 patients potentiate dual functions both raising endosomal pH to slow entry into human cell host infected cells. A live virus-based...