Autor: |
Anna Gidari, Samuele Sabbatini, Elisabetta Schiaroli, Sabrina Bastianelli, Sara Pierucci, Chiara Busti, Lucia Comez, Valeria Libera, Antonio Macchiarulo, Alessandro Paciaroni, Ilaria Vicenti, Maurizio Zazzi, Daniela Francisci |
Jazyk: |
angličtina |
Rok vydání: |
2022 |
Předmět: |
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Zdroj: |
Microorganisms, Vol 10, Iss 7, p 1475 (2022) |
Druh dokumentu: |
article |
ISSN: |
2076-2607 |
DOI: |
10.3390/microorganisms10071475 |
Popis: |
Introduction: The development of effective vaccines has partially mitigated the trend of the SARS-CoV-2 pandemic; however, the need for orally administered antiviral drugs persists. This study aims to investigate the activity of molnupiravir in combination with nirmatrelvir or GC376 on SARS-CoV-2 to verify the synergistic effect. Methods: The SARS-CoV-2 strains 20A.EU, BA.1 and BA.2 were used to infect Vero E6 in presence of antiviral compounds alone or in combinations using five two-fold serial dilution of compound concentrations ≤EC90. After 48 and 72 h post-infection, viability was performed using MTT reduction assay. Supernatants were collected for plaque-assay titration. All experiments were performed in triplicate, each being repeated at least three times. The synergistic score was calculated using Synergy Finder version 2. Results: All compounds reached micromolar EC90. Molnupiravir and GC376 showed a synergistic activity at 48 h with an HSA score of 19.33 (p < 0.0001) and an additive activity at 72 h with an HSA score of 8.61 (p < 0.0001). Molnupiravir and nirmatrelvir showed a synergistic activity both at 48 h and 72 h with an HSA score of 14.2 (p = 0.01) and 13.08 (p < 0.0001), respectively. Conclusion: Molnupiravir associated with one of the two protease-inhibitors nirmatrelvir and GC376 showed good additive-synergic activity in vitro. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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