Cell-based antiviral screening against coronaviruses: developing virus-specific and broad-spectrum inhibitors

Abstract

To combat the public health threat from emerging coronaviruses (CoV), the development of antiviral therapies with either virus-specific or pan-coronaviral activities is necessary. An important step in antiviral drug development is the screening of potential inhibitors in cell-based systems. The recent emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) necessitates adapting methods that have been used to identify antivirals against severe acute respiratory syndrome coronavirus (SARS-CoV) and developing new approaches to more efficiently screen antiviral drugs. In this article we review cell-based assays using infectious virus (BSL-3) and surrogate assays (BSL-2) that can be implemented to accelerate antiviral development against MERS-CoV and future emergent coronaviruses. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses."

Keywords: Antivirals; Entry inhibitors; MERS-CoV; Replicase inhibitors; SARS-CoV; pGlo.

Fig. 1

Coronavirus entry and RNA replication targets for antiviral drug development. Targets for viral entry include the viral spike-host receptor interaction, and host proteases that cleave the viral spike to mediate fusion. Viral replicase polyprotein processing can be targeted by inhibiting the papain-like or 3C-like proteases. The enzymatic activities of the replication-transcription complexes (RTCs) on convoluted membranes and double-membrane vesicles are also attractive targets for inhibitors.