Bioluminescence imaging reveals enhanced SARS-CoV-2 clearance in mice with combinatorial regimens

By Ullah I, Escudie F, Scandale I, Gilani Z, Gendron-Lepage G, Gaudette F, Mowbray C, Fraisse L, Bazin R, Finzi A, Mothes W, Kumar P, Chatelain E, Uchil PD. iScience 2024. doi: 10.1016/j.isci.2024.109049.

Direct acting antivirals (DAAs) are critical tools for combating SARS-CoV-2 variants of concern. The authors of this manuscript used bioluminescence imaging to evaluate the therapeutic efficacy of DAAs favipiravir, molnupiravir, and nirmatrelvir against Delta or Omicron variants of concern in mice. Nirmatrelvir had the best efficacy in suppressing viral loads in the lung, followed by molnupiravir, and favipiravir. Used in monotherapy, these DAAs did not eradicate SARS-CoV-2 in mice. However, when was used in combination, molnupiravir led to virus clearance (with nirmatrelvir), rapid virus clearance and 100% survival (with COVID-19 convalescent plasma), and mitigated inflammation and lung pathology (with caspase-1/4 inhibitor). These insights into the in vivo treatment efficacy of DAAs will help to bolster the COVID-19 therapeutic arsenal.

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