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

Foo, Caroline S.; Abdelnabi, Rana; Kaptein, Suzanne J. F.; Zhang, Xin; ter Horst, Sebastiaan; 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

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.