Open AccessTargeting ectromelia virus and TNF/NF-κB or STAT3 signaling for effective treatment of viral pneumonia
Author(s) -
Pratikshya Pandey,
Zahrah Al Rumaih,
Ma Junaliah Tuazon Kels,
Esther Ng,
Rajendra Kc,
Geeta Chaudhri,
Gunasegaran Karupiah
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2112725119
Subject(s) - ectromelia virus , proinflammatory cytokine , pneumonia , viral pneumonia , virus , immunology , inflammation , medicine , lung , antiviral drug , tumor necrosis factor alpha , virology , biology , disease , infectious disease (medical specialty) , pathology , covid-19 , biochemistry , gene , vaccinia , recombinant dna
Significance Antivirals are ineffective in treating viral pneumonia if administered after 48 h post onset of disease symptoms. Lung pathology during respiratory viral infections is triggered by the host inflammatory response and tissue damage caused by replicating virus. Therefore, targeting both virus and inflammation would be more effective in treating pneumonia. Simultaneous treatment with an anti-inflammatory drug targeting TNF or STAT3 combined with an antiviral drug significantly improved clinical disease, reduced lung viral load and pathology and protected mice from severe pneumonia caused by respiratory ectromelia virus infection. The combined treatment suppressed multiple proinflammatory cytokines and cytokine-signaling pathways, including NF-κB and STAT3. Late after onset of symptoms, antiviral treatment alone cannot ameliorate viral pneumonia, as it cannot reduce inflammation effectively.