Assessing the potential of repurposing ion channel inhibitors to treat emerging viral diseases and the role of this host factor in virus replication.

As diseases caused by new and emerging viruses continue to be a major threat to humans and animals worldwide the need for new therapeutic options intensifies. A wide variety of viruses including Influenza A virus, Human immunodeficiency virus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus require ion channels for efficient replication. Thus, targeting host ion channels may serve as an effective means to attenuate virus replication and help treat viral diseases. Targeting host ion channels is an attractive therapeutic option because a range of ion channel-blocking compounds already exist for the treatment of other human diseases and some of these possess in vitro and sometimes in vivo antiviral activity. Therefore, identifying the specific ion channels involved in replicative cycles could provide opportunities to repurpose these ion channel inhibitors for treating viral diseases. Furthermore, optimised methodologies for identifying effective ion channel targeting drugs and their mechanisms of action could enable rapid responses to newly emerged viruses. This review discusses the potential of ion channels as suitable drug targets to treat diseases caused by viruses by describing known ion channel targeting drugs including their antiviral activity; by summarising prior research demonstrating the requirement for host ion channels for efficient replication of some viruses; and by hypothesising about the role these drugs might play in our ongoing fight against viral diseases.

Inactivation and Recovery of High Quality RNA From Positive SARS-CoV-2 Rapid Antigen Tests Suitable for Whole Virus Genome Sequencing.

The diagnostic protocol currently used globally to identify Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is RT-qPCR. The spread of these infections and the epidemiological imperative to describe variation across the virus genome have highlighted the importance of sequencing. SARS-CoV-2 rapid antigen diagnostic tests (RADTs) are designed to detect viral nucleocapsid protein with positive results suggestive of the presence of replicating virus and potential infectivity. In this study, we developed a protocol for recovering SARS-CoV-2 RNA from "spent" RADT devices of sufficient quality that can be used directly for whole virus genome sequencing. The experimental protocol included the spiking of RADTs at different concentrations with viable SARS-CoV-2 variant Alpha (lineage B.1.1.7), lysis for direct use or storage. The lysed suspensions were used for RNA extraction and RT-qPCR. In parallel, we also tested the stability of the viral RNA in the RADTs and the RNA extracted from the RADTs was used as a template for tiling-PCR and whole virus genome sequencing. RNA recovered from RADTs spiked with SARS-CoV-2 was detected through RT-qPCR with Ct values suitable for sequencing and the recovery from RADTs was confirmed after 7 days of storage at both 4 and 20°C. The genomic sequences obtained at each time-point aligned to the strain used for the spiking, demonstrating that sufficient SARS-CoV-2 viral genome can be readily recovered from positive-RADT devices in which the virus has been safely inactivated and genomically conserved. This protocol was applied to obtain whole virus genome sequence from RADTs ran in the field where the omicron variant was detected. The study demonstrated that viral particles of SARS-CoV-2 suitable for whole virus genome sequencing can be recovered from positive spent RADTs, extending their diagnostic utility, as a risk management tool and for epidemiology studies. In large deployment of the RADTs, positive devices could be safely stored and used as a template for sequencing allowing the rapid identification of circulating variants and to trace the source and spread of outbreaks within communities and guaranteeing public health.