Combined molnupiravir-nirmatrelvir treatment improves the inhibitory effect on SARS-CoV-2 in macaques
dc.contributor.author | Rosenke, K | |
dc.contributor.author | Lewis, MC | |
dc.contributor.author | Feldmann, F | |
dc.contributor.author | Bohrnsen, E | |
dc.contributor.author | Schwarz, B | |
dc.contributor.author | Okumura, A | |
dc.contributor.author | Bohler, WF | |
dc.contributor.author | Callison, J | |
dc.contributor.author | Shaia, C | |
dc.contributor.author | Bosio, CM | |
dc.contributor.author | Lovaglio, J | |
dc.contributor.author | Saturday, G | |
dc.contributor.author | Jarvis, MA | |
dc.contributor.author | Feldmann, H | |
dc.date.accessioned | 2023-06-15T12:27:35Z | |
dc.date.available | 2023-06-15T12:27:35Z | |
dc.date.issued | 2023-02-22 | |
dc.identifier.issn | 2379-3708 | |
dc.identifier.issn | 2379-3708 | |
dc.identifier.other | ARTN e166485 | |
dc.identifier.uri | https://pearl.plymouth.ac.uk/handle/10026.1/20973 | |
dc.description.abstract |
The periodic emergence of SARS-CoV-2 variants of concern (VOCs) with unpredictable clinical severity and ability to escape preexisting immunity emphasizes the continued need for antiviral interventions. Two small molecule inhibitors, molnupiravir (MK-4482), a nucleoside analog, and nirmatrelvir (PF-07321332), a 3C-like protease inhibitor, have recently been approved as monotherapy for use in high-risk patients with COVID-19. As preclinical data are only available for rodent and ferret models, here we assessed the efficacy of MK-4482 and PF-07321332 alone and in combination against infection with the SARS-CoV-2 Delta VOC in the rhesus macaque COVID-19 model. Macaques were infected with the SARS-CoV-2 Delta variant and treated with vehicle, MK-4482, PF-07321332, or a combination of MK-4482 and PF-07321332. Clinical exams were performed at 1, 2, and 4 days postinfection to assess disease and virological parameters. Notably, use of MK-4482 and PF-07321332 in combination improved the individual inhibitory effect of both drugs, resulting in milder disease progression, stronger reduction of virus shedding from mucosal tissues of the upper respiratory tract, stronger reduction of viral replication in the lower respiratory tract, and reduced lung pathology. Our data strongly indicate superiority of combined MK-4482 and PF-07321332 treatment of SARS-CoV-2 infections as demonstrated in the closest COVID-19 surrogate model of human infection. | |
dc.format.extent | e166485- | |
dc.format.medium | Electronic | |
dc.language | en | |
dc.publisher | American Society for Clinical Investigation | |
dc.subject | COVID-19 | |
dc.subject | Drug therapy | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | SARS-CoV-2 | |
dc.subject | Macaca mulatta | |
dc.subject | COVID-19 | |
dc.subject | Ferrets | |
dc.subject | Lactams | |
dc.subject | Leucine | |
dc.subject | Nitriles | |
dc.subject | Antiviral Agents | |
dc.title | Combined molnupiravir-nirmatrelvir treatment improves the inhibitory effect on SARS-CoV-2 in macaques | |
dc.type | journal-article | |
dc.type | Article | |
plymouth.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36574296 | |
plymouth.issue | 4 | |
plymouth.volume | 8 | |
plymouth.publication-status | Published | |
plymouth.journal | JCI Insight | |
dc.identifier.doi | 10.1172/jci.insight.166485 | |
plymouth.organisational-group | |Plymouth | |
plymouth.organisational-group | |Plymouth|Research Groups | |
plymouth.organisational-group | |Plymouth|Faculty of Health | |
plymouth.organisational-group | |Plymouth|Research Groups|Institute of Translational and Stratified Medicine (ITSMED) | |
plymouth.organisational-group | |Plymouth|Research Groups|Institute of Translational and Stratified Medicine (ITSMED)|CBR | |
plymouth.organisational-group | |Plymouth|REF 2021 Researchers by UoA | |
plymouth.organisational-group | |Plymouth|Users by role | |
plymouth.organisational-group | |Plymouth|Users by role|Academics | |
plymouth.organisational-group | |Plymouth|REF 2021 Researchers by UoA|UoA01 Clinical Medicine | |
plymouth.organisational-group | |Plymouth|Faculty of Health|School of Biomedical Sciences | |
dc.publisher.place | United States | |
dcterms.dateAccepted | 2022-12-21 | |
dc.date.updated | 2023-06-15T12:26:57Z | |
dc.rights.embargodate | 2023-6-16 | |
dc.identifier.eissn | 2379-3708 | |
dc.rights.embargoperiod | forever | |
rioxxterms.versionofrecord | 10.1172/jci.insight.166485 |