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

Foo, C. S.; Abdelnabi, R.; Kaptein, S. J. F.; Zhang, X.; ter Horst, S.; Mols, R.; Delang, L.; Rocha-Pereira, J.; Coelmont, L.; Leyssen, P.; Dallmeier, K.; Vergote, V.; Heylen, E.; Vangeel, L.; Chatterjee, A. K.; Annaert, P.; Augustijns, P.; De Jonghe, S.; Jochmans, D.; Weynand, B.; Neyts, J.

doi:10.1101/2021.02.01.429108

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bioRxiv · 10.1101/2021.02.01.429108

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

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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.

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Foo, C. S., Abdelnabi, R., Kaptein, S. J. F., Zhang, X., ter Horst, S., Mols, R., Delang, L., Rocha-Pereira, J., Coelmont, L., Leyssen, P., Dallmeier, K., Vergote, V., Heylen, E., Vangeel, L., Chatterjee, A. K., Annaert, P., Augustijns, P., De Jonghe, S., Jochmans, D., Weynand, B., Neyts, J.. 2021-02-01. Nelfinavir markedly improves lung pathology in SARS-CoV-2-infected Syrian hamsters despite a lack of an antiviral effect. https://doi.org/10.1101/2021.02.01.429108

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