Merafloxacin

Merafloxacin is a fluoroquinolone broad-spectrum antibacterial compound. It is an inhibitor of bacterial DNA gyrase and Type II DNA topoisomerase. It demonstrated excellent activity against Gram-positive organisms and less potent activity against Gram-negative bacteria. Merafloxacin is a programmed -1 ribosomal frameshifting (-1 PRF) inhibitor of SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on -1 PRF of other betacoronaviruses and blocks SARS-CoV-2 replication in Vero E6 cells. The compound reduced viral levels in infected African green monkey VeroE6 cells in a concentration-dependent manner. Merafloxacin showed no cellular toxicity and resulted in a 3 to 4 orders of magnitude reduction of SARS-CoV-2 titer, with IC50 of 4.3 µMu. This compound provides a starting point for high-throughput screening for frameshifting inhibitors as a viable target for therapeutic intervention against SARS-CoV-2.