Coronaviruses (CoV) belong to the large family Coronaviridae within the order of Nidovirales. Among them, several human pathogenic strains (HCoV) are known to mainly cause respiratory diseases. While most strains contribute to common cold-like illnesses others lead to severe infections. Most prominent representatives are SARSCoV and MERS-CoV, which can lead to fatal infections with around 10% and 39% mortality, respectively. This resulted in 8098 casualties in the 2002/2003 SARS-CoV outbreak and in 1806 documented human infections (September 2016) during the recent on-going MERS-CoV outbreak in Saudi Arabia. Currently patients receive treatment focusing on the symptoms connected to the disease rather than addressing the virus as the cause. Therefore, additional treatment options are urgently needed which would ideally be widely available and show a broad affectivity against different human CoVs. Here we show that D, L-lysine acetylsalicylate + glycine sold as “Asprin i.v. 500mg®” (LASAG), which is an approved drug inter alia in the treatment of acute pain, migraine and fever, impairs propagation of different CoV including the highly-pathogenic MERS-CoV in vitro. We demonstrate that the LASAG-dependent impact on virus-induced NF-κB activity coincides with (i) reduced viral titres, (ii) decreased viral protein accumulation and viral RNA synthesis and (iii) impaired formation of viral replication transcription complexes.