Doxycycline inhibits SARS-CoV-2 replication in vitro

Abstract

Introduction and Aim: We examined the effect of pre- and/or post-infection doxycycline on human nasal epithelial cell viability and SARS-CoV-2 (clinical strain IHUMI-3) replication in vitro.  Materials and Methods: Human nasal epithelial cells, an in vivo SARS-CoV-2 target, were derived from healthy donor nasal epithelial stem/progenitor cells via in vitro differentiation. The cells were exposed to doxycycline at 0, 0.1, 0.5, 1, 5, 10, 50, and 100 ?M before and/or after IHUMI-3 inoculation to determine the optimal inhibitory concentration. Viral replication was evaluated using quantitative reverse-transcription PCR, and doxycycline 50% cytotoxic concentration (CC50) and half-maximal effective concentration (EC50) were calculated. The peak serum concentration (Cmax) resulting from typical oral (100 or 200 mg) or intravenous (100 mg) doxycycline doses was estimated, and the Cmax/EC50 ratio was calculated as an index of potential clinical utility.  Results: Doxycycline exhibited low cytotoxicity (CC50 > 100 ?M) in human nasal epithelial cells and inhibited SARS-CoV-2 replication (EC50: 5.2 ± 3.3 ?M) in a dose-dependent manner when administered pre- and/or post-infection. Reasonable oral or intravenous doses will help achieve effective concentrations in vivo.  Conclusion: Early administration of this well-characterized, safe, and accessible drug may limit person-to-person transmission and prevent progression to severe coronavirus disease.