Survival following Ebola virus (EBOV) infection correlates with the ability to mount an early and robust interferon (IFN) response. The host IFN-induced proteins that contribute to controlling EBOV replication are not fully known. Among the top genes with the strongest early increases in expression after infection in vivo is IFN-induced HERC5. Using a transcription- and replication-competent VLP system, we showed that HERC5 inhibits EBOV virus-like particle (VLP) replication by depleting EBOV mRNAs. The HERC5 RCC1-like domain was necessary and sufficient for this inhibition and did not require zinc finger antiviral protein (ZAP). Moreover, we showed that EBOV (Zaire) glycoprotein (GP) but not Marburg virus GP antagonized HERC5 early during infection. Our data identify a novel ‘protagonist–antagonistic’ relationship between HERC5 and GP in the early stages of EBOV infection that could be exploited for the development of novel antiviral therapeutics.

The COVID-19 pandemic has highlighted an urgent need to discover and test new drugs to treat patients. Metal-based drugs are known to interact with DNA and/or a variety of proteins such as enzymes and transcription factors, some of which have been shown to exhibit anticancer and antimicrobial effects. BOLD-100 (sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]dihydrate) is a novel ruthenium-based drug currently being evaluated in a Phase 1b/2a clinical trial for the treatment of advanced gastrointestinal cancer. Given that metal-based drugs are known to exhibit antimicrobial activities, we asked if BOLD-100 exhibits antiviral activity towards SARS-CoV-2. We demonstrated that BOLD-100 potently inhibits SARS-CoV-2 replication and cytopathic effects in vitro. An RNA sequencing analysis showed that BOLD-100 inhibits virus-induced transcriptional changes in infected cells. In addition, we showed that the antiviral activity of BOLD-100 is not specific for SARS-CoV-2, but also inhibits the replication of the evolutionarily divergent viruses Human Immunodeficiency Virus type 1 and Human Adenovirus type 5. This study identifies BOLD-100 as a potentially novel broad-acting antiviral drug.

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Survival following Ebola virus (EBOV) infection correlates with the ability to mount an early and robust interferon (IFN) response. The host IFN-induced proteins that contribute to controlling EBOV replication are not fully known. Among the top genes with the strongest early increases in expression after infection in vivo is IFN-induced HERC5. Using a transcription- and replication-competent VLP system, we showed that HERC5 inhibits EBOV virus-like particle (VLP) replication by depleting EBOV mRNAs. The HERC5 RCC1-like domain was necessary and sufficient for this inhibition and did not require zinc finger antiviral protein (ZAP). Moreover, we showed that EBOV (Zaire) glycoprotein (GP) but not Marburg virus GP antagonized HERC5 early during infection. Our data identifies a novel ‘protagonist-antagonistic’ relationship between HERC5 and GP in the early stages of EBOV infection that could be exploited for the development of novel antiviral therapeutics.

Research Objectives To proactively identify risks that may be exacerbated by the pandemic and mitigate them where possible, a primary care outreach program was developed. Design The screening algorithm was developed by our interdisciplinary Mobility Clinic team, and focuses on 5 domains: health destabilization, mental health, access to services and supports, social isolation, and caregiver stress. The algorithm was administered by phone and any risks identified received further investigation by the team. We used the opportunity to educate patients about the risks of COVID-19 and protective measures. Follow-up continued every 6-8 weeks throughout the duration of the pandemic. Setting The program was developed and implemented in a primary care Mobility Clinic. Participants The algorithm was administered by phone to individuals identified as past and current Mobility Clinic patients. A total of 107 unique patients were contacted, 76 who were male and 31 who were female. 74 patients were identified as having a spinal cord injury (SCI). Interventions Not applicable. Main Outcome Measures An evaluation of this outreach program involved a description of the patient population contacted, the identification of common risks for patients, and patient satisfaction with the program. Results Some of the most common questionnaire responses by patients with SCI included feelings of stress and/or anxiety and a reduction in Personal Support Worker services leading to increased caregiver stress. Conclusions The outreach program helps us to proactively identify risks for individuals with SCI, including stress, anxiety, and decreased Personal Support Worker services. Through the program, we are able to address these concerns and provide follow-up. Risk assessment and care at the primary care level can mitigate adverse events and hospitalizations, which is especially important during a pandemic situation when healthcare and hospital resources are limited. Author(s) Disclosures Dr. James Milligan would like to disclose a relationship with Eisai Pharmaceuticals. Please see the attached disclosure forms for more details. No other authors have any conflicts to disclose.