tetano
Editor, Senior Moderator
iScience
. 2024 Jan 30;27(3):109049.
doi: 10.1016/j.isci.2024.109049. eCollection 2024 Mar 15. Bioluminescence imaging reveals enhanced SARS-CoV-2 clearance in mice with combinatorial regimens
Irfan Ullah[SUP] 1 [/SUP], Fanny Escudie[SUP] 2 [/SUP], Ivan Scandale[SUP] 2 [/SUP], Zoela Gilani[SUP] 3 [/SUP], Gabrielle Gendron-Lepage[SUP] 4 [/SUP], Fleur Gaudette[SUP] 4 [/SUP], Charles Mowbray[SUP] 2 [/SUP], Laurent Fraisse[SUP] 2 [/SUP], Renée Bazin[SUP] 5 [/SUP], Andrés Finzi[SUP] 4 6 [/SUP], Walther Mothes[SUP] 3 [/SUP], Priti Kumar[SUP] 1 [/SUP], Eric Chatelain[SUP] 2 [/SUP], Pradeep D Uchil[SUP] 3 [/SUP]
Affiliations
Direct acting antivirals (DAAs) represent critical tools for combating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have escaped vaccine-elicited spike-based immunity and future coronaviruses with pandemic potential. Here, we used bioluminescence imaging to evaluate therapeutic efficacy of DAAs that target SARS-CoV-2 RNA-dependent RNA polymerase (favipiravir, molnupiravir) or main protease (nirmatrelvir) against Delta or Omicron VOCs in K18-hACE2 mice. Nirmatrelvir displayed the best efficacy followed by molnupiravir and favipiravir in suppressing viral loads in the lung. Unlike neutralizing antibody treatment, DAA monotherapy regimens did not eradicate SARS-CoV-2 in mice, but combining molnupiravir with nirmatrelvir exhibited superior additive efficacy and led to virus clearance. Furthermore, combining molnupiravir with caspase-1/4 inhibitor mitigated inflammation and lung pathology whereas combining molnupiravir with COVID-19 convalescent plasma demonstrated synergy, rapid virus clearance, and 100% survival. Thus, our study provides insights into in vivo treatment efficacies of DAAs and other effective combinations to bolster COVID-19 therapeutic arsenal.
Keywords: Optical imaging; Virology.
. 2024 Jan 30;27(3):109049.
doi: 10.1016/j.isci.2024.109049. eCollection 2024 Mar 15. Bioluminescence imaging reveals enhanced SARS-CoV-2 clearance in mice with combinatorial regimens
Irfan Ullah[SUP] 1 [/SUP], Fanny Escudie[SUP] 2 [/SUP], Ivan Scandale[SUP] 2 [/SUP], Zoela Gilani[SUP] 3 [/SUP], Gabrielle Gendron-Lepage[SUP] 4 [/SUP], Fleur Gaudette[SUP] 4 [/SUP], Charles Mowbray[SUP] 2 [/SUP], Laurent Fraisse[SUP] 2 [/SUP], Renée Bazin[SUP] 5 [/SUP], Andrés Finzi[SUP] 4 6 [/SUP], Walther Mothes[SUP] 3 [/SUP], Priti Kumar[SUP] 1 [/SUP], Eric Chatelain[SUP] 2 [/SUP], Pradeep D Uchil[SUP] 3 [/SUP]
Affiliations
- PMID: 38361624
- PMCID: PMC10867665
- DOI: 10.1016/j.isci.2024.109049
Direct acting antivirals (DAAs) represent critical tools for combating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have escaped vaccine-elicited spike-based immunity and future coronaviruses with pandemic potential. Here, we used bioluminescence imaging to evaluate therapeutic efficacy of DAAs that target SARS-CoV-2 RNA-dependent RNA polymerase (favipiravir, molnupiravir) or main protease (nirmatrelvir) against Delta or Omicron VOCs in K18-hACE2 mice. Nirmatrelvir displayed the best efficacy followed by molnupiravir and favipiravir in suppressing viral loads in the lung. Unlike neutralizing antibody treatment, DAA monotherapy regimens did not eradicate SARS-CoV-2 in mice, but combining molnupiravir with nirmatrelvir exhibited superior additive efficacy and led to virus clearance. Furthermore, combining molnupiravir with caspase-1/4 inhibitor mitigated inflammation and lung pathology whereas combining molnupiravir with COVID-19 convalescent plasma demonstrated synergy, rapid virus clearance, and 100% survival. Thus, our study provides insights into in vivo treatment efficacies of DAAs and other effective combinations to bolster COVID-19 therapeutic arsenal.
Keywords: Optical imaging; Virology.