Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Remdesivir-Nirmatrelvir Combination: In Vitro Activity and a Case Report

Anna Gidari
* ,
Samuele Sabbatini
,
Elisabetta Schiaroli
,
Sabrina Bastianelli
ORCID logo ,
Sara Pierucci
ORCID logo ,
Chiara Busti
,
Lavinia Maria Saraca
,
Luca Capogrossi
,
Maria Bruna Pasticci
,
Daniela Francisci
Version 1 : Received: 31 May 2023 / Approved: 1 June 2023 / Online: 1 June 2023 (08:00:38 CEST)

A peer-reviewed article of this Preprint also exists.

Gidari, A.; Sabbatini, S.; Schiaroli, E.; Bastianelli, S.; Pierucci, S.; Busti, C.; Saraca, L.M.; Capogrossi, L.; Pasticci, M.B.; Francisci, D. Synergistic Activity of Remdesivir–Nirmatrelvir Combination on a SARS-CoV-2 In Vitro Model and a Case Report. Viruses 2023, 15, 1577. Gidari, A.; Sabbatini, S.; Schiaroli, E.; Bastianelli, S.; Pierucci, S.; Busti, C.; Saraca, L.M.; Capogrossi, L.; Pasticci, M.B.; Francisci, D. Synergistic Activity of Remdesivir–Nirmatrelvir Combination on a SARS-CoV-2 In Vitro Model and a Case Report. Viruses 2023, 15, 1577.

Abstract

Introduction: This study aims to investigate the activity of the remdesivir-nirmatrelvir combination against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and to report a case of Coronavirus Disease 2019 (COVID-19) cured with this combination. Methods: A Vero E6 cell-based infection assay was used to investigate the in vitro activity of the remdesivir-nirmatrelvir combination. The SARS-CoV-2 strains tested were 20A.EU1, BA.1 and BA.5. After incubation, a viability assay was performed. The supernatants were collected and used for viral titration. The Highest Single Agent (HSA) reference model was calculated. An HSA score >10 is considered synergic. Results: Remdesivir and nirmatrelvir showed synergistic activity at 48 and 72 h with an HSA score of 52.8 and 28.6, respectively (p<0.0001). This data has been confirmed performing supernatant titration and against the omicron variants: the combination reduced the viral titer better than the more active compound alone. An immunocompromised patient with prolonged and critical COVID-19 was successfully treated with remdesivir, nirmatrelvir/ritonavir, tixagevimab/cilgavimab, and dexamethasone, with an excellent clinical-radiological response. However, she required further off-label prolonged therapy with nirmatrelvir/ritonavir up to the negativization. Conclusion: Remdesivir-nirmatrelvir combination has synergic activity in vitro. This combination may have a role in immunosuppressed patients with severe COVID-19 and prolonged viral shedding.

Keywords

COVID-19; SARS-CoV-2; remdesivir; nirmatrelvir; variant; synergy; antiviral; immunosuppressed

Subject

Medicine and Pharmacology, Epidemiology and Infectious Diseases

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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