Article ; Online: In Vitro Combinatorial Activity of Direct Acting Antivirals and Monoclonal Antibodies against the Ancestral B.1 and BQ.1.1 SARS-CoV-2 Viral Variants.
2024 Volume 16, Issue 2
Abstract: Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection; however, no clinical trial data are available, and combined use of direct-acting antivirals (DAA) and monoclonal antibodies (mAb) has been reported only anecdotally. ... ...
Abstract | Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection; however, no clinical trial data are available, and combined use of direct-acting antivirals (DAA) and monoclonal antibodies (mAb) has been reported only anecdotally. To assess the cooperative effects of dual drug combinations in vitro, we used a VERO E6 cell-based in vitro system with the ancestral B.1 or the highly divergent BQ.1.1 virus to test pairwise combinations of the licensed DAA, including nirmatrelvir (NRM), remdesivir (RDV) and the active metabolite of molnupiravir (EIDD-1931) as well the combination of RDV with four licensed mAbs (sotrovimab, bebtelovimab, cilgavimab, tixagevimab; tested only with the susceptible B.1 virus). According to SynergyFinder 3.0 summary and weighted scores, all the combinations had an additive effect. Within DAA/DAA combinations, paired scores with the B.1 and BQ.1.1 variants were comparable. In the post hoc analysis weighting synergy by concentrations, several cases of highly synergistic scores were detected at specific drug concentrations, both for DAA/DAA and for RDV/mAb combinations. This was supported by in vitro confirmation experiments showing a more than a linear shift of a drug-effective concentration (IC |
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MeSH term(s) | Animals ; SARS-CoV-2/genetics ; Antiviral Agents/pharmacology ; COVID-19 ; Hepatitis C, Chronic ; Antibodies, Monoclonal/pharmacology ; Drug Combinations |
Chemical Substances | Antiviral Agents ; Antibodies, Monoclonal ; Drug Combinations |
Language | English |
Publishing date | 2024-01-23 |
Publishing country | Switzerland |
Document type | Journal Article |
ZDB-ID | 2516098-9 |
ISSN | 1999-4915 ; 1999-4915 |
ISSN (online) | 1999-4915 |
ISSN | 1999-4915 |
DOI | 10.3390/v16020168 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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