A5003788917- SARS-CoV-2 and COVID-19 Research
- Herpesvirus Infections and Treatments
- interferon and immune responses
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- COVID-19 Clinical Research Studies
- Animal Virus Infections Studies
- Respiratory viral infections research
- Hepatitis C virus research
- PARP inhibition in cancer therapy
- Cytomegalovirus and herpesvirus research
- Hepatitis B Virus Studies
- Liver Disease Diagnosis and Treatment
- Lung Cancer Diagnosis and Treatment
- CRISPR and Genetic Engineering
- SARS-CoV-2 detection and testing
- Influenza Virus Research Studies
- HIV Research and Treatment
- Viral gastroenteritis research and epidemiology
- Metabolomics and Mass Spectrometry Studies
- Cardiovascular Function and Risk Factors
- Synthesis and Characterization of Heterocyclic Compounds
- Cancer Diagnosis and Treatment
- RNA regulation and disease
- Heart Failure Treatment and Management
California Institute for Biomedical Research
2021-2025
Torrey Pines Institute For Molecular Studies
2024-2025
Scripps Research Institute
2021-2025
Discovery Institute
2019-2024
Sanford Burnham Prebys Medical Discovery Institute
2019-2024
Azienda Ospedaliera G. Brotzu
2023
Scripps Institution of Oceanography
2023
Scripps (United States)
2023
Azienda di Rilievo Nazionale ed Alta Specializzazione
2022
Institut Pasteur de Lille
2015-2021
Recent studies have profiled the innate immune signatures in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and suggest that cellular responses to viral challenge may affect disease severity. Yet molecular events underlie recognition response SARS-CoV-2 infection remain be elucidated. Here, we find replication induces a delayed interferon (IFN) lung epithelial cells. By screening 16 putative sensors involved sensing of RNA virus infection, found MDA5 LGP2...
The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by coronavirus, following emergence severe acute respiratory syndrome (SARS) in 20031 and Middle East (MERS) 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine—an anti-leprosy drug with favourable safety profile3—possesses inhibitory activity against several coronaviruses, can antagonize replication SARS-CoV-2 MERS-CoV range vitro systems. We found molecule, which has been...
Abstract The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline discovery of efficacious SARS-CoV-2 inhibitors. We screen best-in-class repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing receptor ACE2 other lung...
The NLRP3 inflammasome is involved in many obesity-associated diseases, such as type 2 diabetes, atherosclerosis, and gouty arthritis, through its ability to induce interleukin (IL)-1β release. molecular link between obesity activation still unclear, but free fatty acids have been proposed one triggering event. Here we reported opposite effects of saturated (SFAs) compared with unsaturated (UFAs) on human monocytes/macrophages. Palmitate stearate, both SFAs, triggered IL-1β secretion a...
Abstract The emergence of novel SARS coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic severe pneumonia-like disease designated as (COVID-19). To date, more than 2.1 million confirmed cases and 139,500 deaths have been reported worldwide, there are currently no medical countermeasures available to prevent or treat the disease. As development a vaccine could require at least 12-18 months, typical timeline from hit finding drug registration antiviral is >10 years,...
SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified small-molecule library of 34 430 protein kinase inhibitors that were capable inhibiting cytopathic effect in human epithelial cells. These drug are various stages clinical trials. detected key proteins involved cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, DNA-damage response critical for infection. A drug-protein interaction-based...
There remains a need to develop novel SARS-CoV-2 therapeutic options that improve upon existing therapies by an increased robustness of response, fewer safety liabilities, and global-ready accessibility. Functionally critical viral main protease (Mpro, 3CLpro) is attractive target due its homology within the coronaviral family, lack thereof toward human proteases. In this disclosure, we outline advent 3CLpro inhibitor, CMX990, bearing unprecedented trifluoromethoxymethyl ketone warhead....
In hepatitis C virus (HCV)-infected cells, the envelope glycoproteins E1 and E2 assemble as a heterodimer. To investigate potential changes in oligomerization of virion-associated proteins, we performed SDS-PAGE under reducing conditions but without thermal denaturation. This revealed presence SDS-resistant trimers context cell-cultured HCV (HCVcc) well pseudoparticles (HCVpp). The formation was found to depend on coexpression E2. further understand origin trimer formation, coexpressed...
Many respiratory viruses attack the airway epithelium and cause a wide spectrum of diseases for which we have limited therapies. To date, few primary human stem cell-based models proximal been reported drug discovery but scaling them up to higher throughput platform remains significant challenge. As result, most screening assays are performed on commercial cell line-based 2D cultures that provide translational ability. We optimized mucociliary model SARS-CoV-2 infection, in 96-well...
The pandemic threat from newly emerging viral diseases constitutes a major unsolved issue for global health. Antiviral therapy can play an important role in treating and preventing the spread of unprecedented infections. A repository compounds exhibiting broad-spectrum antiviral activity against series different families would be invaluable asset to prepared future threats. Utilizing open innovation crowd-sourcing paradigm, we were able identify compound class diphenylureas that exhibits...
Abstract COVID-19 pandemic is the third zoonotic coronavirus (CoV) outbreak of century after severe acute respiratory syndrome (SARS) in 2003 and Middle East (MERS) since 2012. Treatment options for CoVs are largely lacking. Here, we show that clofazimine, an anti-leprosy drug with a favorable safety pharmacokinetics profile, possesses pan-coronaviral inhibitory activity, can antagonize SARS-CoV-2 replication multiple vitro systems, including human embryonic stem cell-derived cardiomyocytes...
Zika virus (ZIKV) is a mosquito-borne pathogen classified by the World Health Organization (WHO) as public health emergency of international concern in 2016, and it still identified priority disease. Although most infected individuals are asymptomatic or show mild symptoms, risk neurologic complications associated with infection adults. Additionally, during pregnancy directly linked to microcephaly other congenital malformations. Since there no currently available vaccines approved...
There is a pressing need for host-directed therapeutics that elicit broad-spectrum antiviral activities to potentially address current and future viral pandemics. Apratoxin S4 (Apra S4) potent Sec61 inhibitor prevents cotranslational translocation of secretory proteins into the endoplasmic reticulum (ER), leading anticancer antiangiogenic activity both in vitro vivo. Since has been shown be an essential host factor proteostasis, we tested Apra cellular models infection, including SARS-CoV-2,...
Recent studies profiling the innate immune signatures in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggest that cellular responses to viral challenge impact disease severity. Yet, molecular events underlie recognition and response SARS-CoV-2 infection remains be elucidated. Here, we find replication induces a delayed interferon (IFN) lung epithelial cells. Through survey of putative sensors involved detection RNA virus infection, found MDA5 LGP2...
ABSTRACT The role of the tegument during herpesvirus lytic cycle is still not clearly established, particularly at late phase infection, when newly produced viral particles need to be fully assembled before being released from infected cell. varicella-zoster virus (VZV) protein coded by open reading frame (ORF) 9 (ORF9p) an essential protein, and, even though its mRNA most expressed productive little known about functions. Using a GalK positive/negative selection technique, we modified...
Herpesviruses are responsible for infections that, especially in immunocompromised patients, can lead to severe complications, including neurological symptoms and strokes. The constant emergence of viral strains resistant classical antivirals (mainly acyclovir its derivatives) pleads the identification new targets future antiviral treatments. Cellular adaptor protein (AP) complexes have been implicated correct addressing herpesvirus glycoproteins infected cells, discovery that a major...
Novel strategies are needed to identify drug targets and treatments for the COVID-19 pandemic. The altered gene expression of virus-infected host cells provides an opportunity specifically inhibit viral propagation via targeting synthetic lethal dosage (SL/SDL) partners such genes. Pursuing this disparate antiviral strategy, here we comprehensively analyzed multiple