A5073248934- SARS-CoV-2 and COVID-19 Research
- Respiratory viral infections research
- COVID-19 Clinical Research Studies
- Viral Infections and Immunology Research
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 detection and testing
- interferon and immune responses
- Hepatitis C virus research
- Bacteriophages and microbial interactions
- HIV/AIDS drug development and treatment
- Viral-associated cancers and disorders
- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- Viral Infections and Outbreaks Research
- Extracellular vesicles in disease
- Influenza Virus Research Studies
- Cytomegalovirus and herpesvirus research
- Animal Virus Infections Studies
- Immunodeficiency and Autoimmune Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Viral Infections and Vectors
- Hepatitis B Virus Studies
- Monoclonal and Polyclonal Antibodies Research
- Biosensors and Analytical Detection
- Polyomavirus and related diseases
Gilead Sciences (United States)
2020-2025
Gilead Sciences (France)
2020-2021
United States Military Academy
2017
Merck & Co., Inc., Rahway, NJ, USA (United States)
2017
Idera Pharmaceuticals (United States)
2008-2014
Harvard University
2006-2011
New England Biolabs (United States)
2006-2011
Instituto de Salud Carlos III
2011
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2011
Austin Hospital
2011
The pathogenic lymphocryptovirus Epstein–Barr virus (EBV) is shown to express at least 17 distinct microRNAs (miRNAs) in latently infected cells. These are arranged two clusters: 14 miRNAs located the introns of viral BART gene while three adjacent BHRF1. expressed high levels epithelial cells and lower, albeit detectable, B In contrast tissue-specific expression pattern miRNAs, BHRF1 found undergoing stage III latency but essentially undetectable or I II latency. Induction lytic EBV...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of novel viral disease COVID-19. With no approved therapies, this pandemic illustrates urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits replication in human lung cells primary airway epithelial cultures (EC50 = 0.01 μM). Weaker activity observed Vero E6 1.65 μM) because their low capacity to metabolize RDV....
Abstract A high-throughput platform would greatly facilitate coronavirus disease 2019 (COVID-19) serological testing and antiviral screening. Here we present a nanoluciferase severe respiratory syndrome 2 (SARS-CoV-2-Nluc) that is genetically stable replicates similarly to the wild-type virus in cell culture. SARS-CoV-2-Nluc can be used measure neutralizing antibody activity patient sera within 5 hours, it produces results concordance with plaque reduction neutralization test (PRNT)....
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...
A spike protein mutation D614G became dominant in SARS-CoV-2 during the COVID-19 pandemic. However, mutational impact on viral spread and vaccine efficacy remains to be defined. Here we engineer USA-WA1/2020 strain characterize its effect replication, pathogenesis, antibody neutralization. The significantly enhances replication human lung epithelial cells primary airway tissues, through an improved infectivity of virions with receptor-binding domain "up" conformation for binding ACE2...
The coronavirus disease 2019 (COVID-19) pandemic remains uncontrolled despite the rapid rollout of safe and effective severe acute respiratory syndrome 2 (SARS-CoV-2) vaccines, underscoring need to develop highly antivirals. In setting waning immunity from infection vaccination, breakthrough infections are becoming increasingly common treatment options remain limited. addition, emergence SARS-CoV-2 variants concern, with their potential escape neutralization by therapeutic monoclonal...
Genetic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence and rapid spread multiple variants throughout pandemic, which Omicron is currently predominant variant circulating worldwide. SARS-CoV-2 concern/variants interest (VOC/VOI) have evidence increased viral transmission, disease severity, or decreased effectiveness vaccines neutralizing antibodies. Remdesivir (RDV [VEKLURY]) a nucleoside analog prodrug first FDA-approved antiviral...
A discovery program targeting respiratory syncytial virus (RSV) identified
Abstract Remdesivir (GS-5734; VEKLURY) is a single diastereomer monophosphoramidate prodrug of an adenosine analog (GS-441524). taken up by target cells and metabolized in multiple steps to form the active nucleoside triphosphate (GS-443902), which acts as potent inhibitor viral RNA-dependent RNA polymerases. GS-441524 have antiviral activity against viruses. Here, we expand evaluation remdesivir’s members families Flaviviridae , Picornaviridae Filoviridae Orthomyxoviridae Hepadnaviridae....
Remdesivir 1 is an phosphoramidate prodrug that releases the monophosphate of nucleoside GS-441524 (2) into lung cells, thereby forming bioactive triphosphate 2-NTP. 2-NTP, analog ATP, inhibits SARS-CoV-2 RNA-dependent RNA polymerase replication and transcription viral RNA. Strong clinical results for have prompted interest in oral approaches to generate Here, we describe discovery a 5′-isobutyryl ester 2 (GS-5245, Obeldesivir, 3) has low cellular cytotoxicity 3–7-fold improved delivery...
Obeldesivir (ODV, GS-5245) is an orally administered prodrug of the parent nucleoside remdesivir (RDV) and presently in phase 3 trials for COVID-19 treatment. In this work, we show that ODV its circulating metabolite, GS-441524, have similar vitro antiviral activity against filoviruses, including Marburg virus, Ebola Sudan virus (SUDV). We also report once-daily oral treatment cynomolgus monkeys 10 days beginning 24 hours after SUDV exposure confers 100% protection lethal infection....
There are, besides remdesivir, no approved antivirals for the treatment of SARS-CoV-2 infections. To aid in search against this virus, we explored use human tracheal airway epithelial cells (HtAEC) and small (HsAEC) grown at air-liquid interface (ALI). These cultures were infected apical side with one two different isolates. Each virus was shown to replicate high titers extended periods time (at least 8 days) and, particular an isolate D614G spike (S) protein did so more efficiently 35 °C...
Remdesivir (RDV; GS-5734, Veklury), the first FDA-approved antiviral to treat COVID-19, is a single-diastereomer monophosphoramidate prodrug of an adenosine analogue. RDV taken up in target cells and metabolized multiple steps form active nucleoside triphosphate (TP) (GS-443902), which, turn, acts as potent selective inhibitor viral RNA polymerases.
Despite the wide availability of several safe and effective vaccines that prevent severe COVID-19, persistent emergence acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants concern (VOCs) can evade vaccine-elicited immunity remains a global health concern. In addition, SARS-CoV-2 VOCs therapeutic monoclonal antibodies underscores need for additional, variant-resistant treatment strategies. Here, we characterize antiviral activity GS-5245, obeldesivir (ODV), an oral prodrug parent...
A spike protein mutation D614G became dominant in SARS-CoV-2 during the COVID-19 pandemic. However, mutational impact on viral spread and vaccine efficacy remains to be defined. Here we engineer USA-WA1/2020 strain characterize its effect replication, pathogenesis, antibody neutralization. The significantly enhances replication human lung epithelial cells primary airway tissues, through an improved infectivity of virions with receptor-binding domain "up" conformation for binding ACE2...
The SARS-CoV-2 replication-transcription complex is an assembly of nonstructural viral proteins that collectively act to reproduce the genome and generate mRNA transcripts. While structures individual involved are known, how they assemble into a functioning superstructure not. Applying molecular modeling tools, including protein-protein docking, available nsp7-nsp16 nucleocapsid, we have constructed atomistic model these associate. Our principal finding hexameric, centered on nsp15. nsp15...
Remdesivir (RDV) is a nucleotide analog prodrug with demonstrated clinical benefit in patients coronavirus disease 2019 (COVID-19). In October 2020, the US FDA approved intravenous (IV) RDV as first treatment for hospitalized COVID-19 patients. Furthermore, has been or authorized emergency use more than 50 countries. To make convenient non-hospitalized earlier disease, alternative routes of administration are being evaluated. Here, we investigated pharmacokinetics and efficacy administered...
SUMMARY Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as the causative agent of novel pandemic viral disease COVID-19. With no approved therapies, this illustrates urgent need for safe, broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV), a monophosphoramidate prodrug an adenosine analog, potently inhibits replication human lung cells primary airway epithelial cultures (EC 50 = 0.01 μM). Weaker...
Remdesivir (RDV) is a direct-acting antiviral agent that approved in several countries for the treatment of coronavirus disease 2019 caused by severe acute respiratory syndrome 2. RDV exhibits broad-spectrum activity against positive-sense RNA viruses, example, and hepatitis C virus, nonsegmented negative-sense Nipah whereas segmented viruses such as influenza virus or Crimean-Congo hemorrhagic fever are not sensitive to drug. The reasons this apparent efficacy pattern unknown. Here, we...
Abstract A high-throughput platform would greatly facilitate COVID-19 serological testing and antiviral screening. Here we report a nanoluciferase SARS-CoV-2 (SARS-CoV-2-Nluc) that is genetically stable replicates similarly to the wild-type virus in cell culture. We demonstrate optimized reporter assay Vero E6 cells can be used measure neutralizing antibody activity patient sera produces results concordance with plaque reduction neutralization test (PRNT). Compared low-throughput PRNT (3...
Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, emergence SARS-CoV-2 variants concern (VOC) partially evade vaccine immunity remains a global health concern. In addition, highly mutated neutralization-resistant VOCs such as BA.1 BA.5 or fully (1) many therapeutic monoclonal antibodies in clinical use underlines need for additional treatment strategies. Here, we characterize antiviral activity GS-5245, Obeldesivir (ODV), an oral...