Combination Therapy with UV-4B and Molnupiravir Enhances SARS-CoV-2 Suppression.
Viruses
; 15(5)2023 05 16.
Artigo
em Inglês
| MEDLINE | ID: covidwho-20235667
ABSTRACT
The host targeting antiviral, UV-4B, and the RNA polymerase inhibitor, molnupiravir, are two orally available, broad-spectrum antivirals that have demonstrated potent activity against SARS-CoV-2 as monotherapy. In this work, we evaluated the effectiveness of UV-4B and EIDD-1931 (molnupiravir's main circulating metabolite) combination regimens against the SARS-CoV-2 beta, delta, and omicron BA.2 variants in a human lung cell line. Infected ACE2 transfected A549 (ACE2-A549) cells were treated with UV-4B and EIDD-1931 both as monotherapy and in combination. Viral supernatant was sampled on day three when viral titers peaked in the no-treatment control arm, and levels of infectious virus were measured by plaque assay. The drug-drug effect interaction between UV-4B and EIDD-1931 was also defined using the Greco Universal Response Surface Approach (URSA) model. Antiviral evaluations demonstrated that treatment with UV-4B plus EIDD-1931 enhanced antiviral activity against all three variants relative to monotherapy. These results were in accordance with those obtained from the Greco model, as these identified the interaction between UV-4B and EIDD-1931 as additive against the beta and omicron variants and synergistic against the delta variant. Our findings highlight the anti-SARS-CoV-2 potential of UV-4B and EIDD-1931 combination regimens, and present combination therapy as a promising therapeutic strategy against SARS-CoV-2.
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Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
MEDLINE
Assunto principal:
Enzima de Conversão de Angiotensina 2
/
COVID-19
Tipo de estudo:
Estudo experimental
Tópicos:
Variantes
Limite:
Humanos
Idioma:
Inglês
Ano de publicação:
2023
Tipo de documento:
Artigo
País de afiliação:
V15051175
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