Nelfinavir markedly improves lung pathology in SARS-CoV-2-infected Syrian hamsters despite lack of an antiviral effect

Abstract In response to the ongoing COVID-19 pandemic, repurposing of drugs for the treatment of SARS-CoV-2 infections is being explored. The HIV protease inhibitor Nelfinavir, widely prescribed in combination with other HIV inhibitors, has been shown to inhibit in vitro SARS-CoV-2 replication. We h...

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Published in:bioRxiv 2021-03
Main Authors: Foo, Caroline S, Rana Abdelnabi, Kaptein, Suzanne J F, Zhang, Xin, Sebastiaan Ter Horst, Mols, Raf, Delang, Leen, Rocha-Pereira, Joana, Coelmont, Lotte, Leyssen, Pieter, Dallmeier, Kai, Vergote, Valentijn, Heylen, Elisabeth, Vangeel, Laura, Chatterjee, Arnab K, Annaert, Pieter, Augustijns, Patrick, De Jonghe, Steven, Jochmans, Dirk, Weynand, Birgit, Neyts, Johan
Format: Article
Language:English
Subjects:
Antiviral agents
COVID-19
HIV
Human immunodeficiency virus
Leukocytes (neutrophilic)
Lungs
Microbiology
Nelfinavir
Pandemics
Pathology
Proteinase inhibitors
RNA viruses
Severe acute respiratory syndrome coronavirus 2
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Summary:Abstract In response to the ongoing COVID-19 pandemic, repurposing of drugs for the treatment of SARS-CoV-2 infections is being explored. The HIV protease inhibitor Nelfinavir, widely prescribed in combination with other HIV inhibitors, has been shown to inhibit in vitro SARS-CoV-2 replication. We here report on the effect of Nelfinavir in the Syrian hamster SARS-CoV-2 infection model. Although treatment of infected hamsters with either 15 or 50 mg/kg BID Nelfinavir [for four consecutive days, initiated on the day of infection] does not reduce viral RNA loads nor infectious virus titres in the lungs compared to the vehicle control, the drug reduced virus-induced lung pathology to nearly the baseline scores of healthy animals. A substantial interstitial infiltration of neutrophils is observed in the lungs of treated (both infected and uninfected) animals. The protective effect of Nelfinavir on SARS-CoV-2-induced lung pathology (at doses that are well tolerated and that result in exposures nearing those observed in HIV-infected patients) may lay the foundation for clinical studies with this widely used drug. Competing Interest Statement The authors have declared no competing interest. Footnotes
ISSN:2692-8205
DOI:10.1101/2021.02.01.429108