A5033824669- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Respiratory viral infections research
- Viral Infections and Immunology Research
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- Poxvirus research and outbreaks
- PARP inhibition in cancer therapy
- Virology and Viral Diseases
- Rabies epidemiology and control
- Viral Infections and Outbreaks Research
- HIV/AIDS drug development and treatment
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Animal Virus Infections Studies
- Calcium signaling and nucleotide metabolism
- HIV Research and Treatment
- Polyomavirus and related diseases
- Microbial infections and disease research
- Tuberculosis Research and Epidemiology
Gilead Sciences (United States)
2020-2023
Georgia State University
2019-2020
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....
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
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...
In vitro selection of remdesivir-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed the emergence a V166L substitution, located outside polymerase active site Nsp12 protein, after 9 passages single lineage. remained only substitution 17 (10 μM remdesivir), conferring 2.3-fold increase in 50% effective concentration (EC 50 ).
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...
Measles virus (MeV) is a highly contagious, re-emerging, major human pathogen. Replication requires viral RNA-dependent RNA polymerase (RdRP) consisting of the large (L) protein complexed with homo-tetrameric phosphoprotein (P). In addition, P mediates interaction nucleoprotein (N)-encapsidated genome. The nature P:L interface and RdRP negotiation ribonucleoprotein template are poorly understood. Based on biochemical mapping, swapping central tetramerization domain (OD) for yeast GCN4,...
The COVID-19 pandemic remains uncontrolled despite the rapid rollout of safe and effective 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. Additionally, emergence variants concern with their potential escape therapeutic monoclonal antibodies emphasizes second-generation oral antivirals targeting conserved viral proteins that...
The urgent response to the COVID-19 pandemic required accelerated evaluation of many approved drugs as potential antiviral agents against causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using cell-based, biochemical, and modeling approaches, we studied HIV-1 nucleoside/tide reverse transcriptase inhibitors (NRTIs) tenofovir (TFV) emtricitabine (FTC), well prodrugs alafenamide (TAF) disoproxilfumarate (TDF) for their effect SARS-CoV-2. A comprehensive set in...
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 (EC50 = 0.01 µM). Weaker activity...
Abstract Remdesivir 1 is an amidate prodrug that releases the monophosphate of nucleoside GS-441524 ( 2 ) into lung cells thereby forming bioactive triphosphate 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 GS-5245, Obeldesivir, 3 has low cellular cytotoxicity three seven-fold improved delivery...
Rabies virus (RABV) causes a severe and fatal neurological disease, but morbidity is vaccine preventable treatable prior to the onset of clinical symptoms. However, immunoglobulin (IgG)-based rabies postexposure prophylaxis (PEP) expensive, restricting access life-saving treatment, especially for patients in low-income countries where need greatest, does not confer cross-protection against newly emerging phylogroup II lyssaviruses. Toward identifying cost-effective replacement IgG component...
Abstract Background Remdesivir (RDV, Veklury) is the first FDA-approved direct-acting antiviral treatment for COVID-19. While RDV requires IV administration, obeldesivir (ODV, GS-5245) an oral prodrug of GS-441524, parent nucleoside RDV, designed effective delivery. ODV being tested in two Phase 3 clinical studies outpatient Methods In vitro activity against SARS-CoV-2 was assessed A549-hACE2 cells. vivo therapeutic efficacy evaluated mouse, ferret, and African Green Monkey (AGM) models....
Abstract In vitro selection of remdesivir-resistant SARS-CoV-2 revealed the emergence a V166L substitution, located outside polymerase active site nsp12 protein, after 9 passages. remained only substitution 17 passages at final concentration 10 µM RDV, conferring 2.3-fold increase in EC 50 . When was introduced into recombinant virus, 1.5-fold observed, indicating high barrier to RDV resistance.
Abstract Genetic variation of SARS-CoV-2 has resulted in the emergence and rapid spread multiple variants throughout pandemic, which Omicron is currently predominant variant circulating worldwide. concern or interest (VOC/VOI) have evidence increased viral transmission, disease severity, decreased effectiveness vaccines neutralizing antibodies. Remdesivir (RDV, VEKLURY ® ) a nucleoside analog prodrug first FDA-approved antiviral treatment COVID-19. Here we present comprehensive activity...
Abstract Remdesivir is the only small-molecule antiviral approved to date for COVID-19 treatment, but its wider use limited by intravenous delivery. An orally bioavailable remdesivir analog may boost therapeutic benefit facilitating early administration non-hospitalized patients. This study characterized anti-SARS-CoV-2 efficacy of GS-621763, an oral prodrug parent nucleoside GS-441524. Both GS-621763 and GS-441524 inhibited SARS-CoV-2, including variants concern (VoC) in cell culture. Oral...