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Early therapy with remdesivir and antibody combinations improves COVID-19 disease in mice
David Martinez; Alexandra Schaefer; Sarah R. Leist; Dapeng Li; Kendra Gully; Joy Feng; Elaine Bunyan; Danielle Porter; Tomas Cihlar; Stephanie Montgomery; Barton Haynes; Ralph S. Baric; Michel C. Nussenzweig; Timothy P. Sheahan.
Affiliation
  • David Martinez; The University of North Carolina at Chapel Hill
  • Alexandra Schaefer; University of North Carolina at Chapel Hill
  • Sarah R. Leist; University of North Carolina at Chapel Hill
  • Dapeng Li; Duke University
  • Kendra Gully; University of North Carolina at Chapel Hill
  • Joy Feng; Gilead Sciences Inc
  • Elaine Bunyan; Gilead Sciences Inc
  • Danielle Porter; Gilead Sciences Inc
  • Tomas Cihlar; Gilead Sciences Inc
  • Stephanie Montgomery; University of North Carolina at Chapel Hill
  • Barton Haynes; Duke University
  • Ralph S. Baric; University of North Carolina at Chapel Hill
  • Michel C. Nussenzweig; The Rockefeller University
  • Timothy P. Sheahan; University of North Carolina at Chapel Hill
Preprint in English | bioRxiv | ID: ppbiorxiv-428478
ABSTRACT
Improving the standard of clinical care for individuals infected with SARS-CoV-2 variants is a global health priority. Small molecule antivirals like remdesivir (RDV) and biologics such as human monoclonal antibodies (mAb) have demonstrated therapeutic efficacy against SARS-CoV-2, the causative agent of COVID-19. However, it is not known if combination RDV/mAb will improve outcomes over single agent therapies or whether antibody therapies will remain efficacious against variants. In kinetic studies in a mouse-adapted model of ancestral SARS-CoV-2 pathogenesis, we show that a combination of two mAbs in clinical trials, C144 and C135, have potent antiviral effects against even when initiated 48 hours after infection. The same antibody combination was also effective in prevention and therapy against the B.1.351 variant of concern (VOC). Combining RDV and antibodies provided a modest improvement in outcomes compared to single agents. These data support the continued use of RDV to treat SARS-CoV-2 infections and support the continued clinical development of the C144 and C135 antibody combination to treat patients infected with SARS-CoV-2 variants.
License
cc_by_nc_nd
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2021 Document type: Preprint
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