Mono- and combinational drug therapies for global viral pandemic preparedness

Broadly effective antiviral therapies must be developed to be ready for clinical trials, which should begin soon after the emergence of new life-threatening viruses. Here, we pave the way towards this goal by reviewing conserved druggable virus-host interactions, mechanisms of action, immunomodulatory properties of available broad-spectrum antivirals (BSAs), routes of BSA delivery, and interactions of BSAs with other antivirals. Based on the review, we concluded that the range of indications of BSAs can be expanded, and new pan- and cross-viral mono- and combinational therapies can be developed. We have also developed a new scoring algorithm that can help identify the most promising few of the thousands of potential BSAs and BSA-containing drug cocktails (BCCs) to prioritize their development during the critical period between the identification of a new virus and the development of virus-specific vaccines, drugs, and therapeutic antibodies.Peer reviewe

Diffuse Leptomeningeal Glioneuronal Tumour with 9-Year Follow-Up: Case Report and Review of the Literature

In 2016, the World Health Organisation Classification (WHO) of Tumours was updated with diffuse leptomeningeal glioneuronal tumour (DLGNT) as a provisional unit of mixed neuronal and glial tumours. Here, we report a DLGNT that has been re-diagnosed with the updated WHO classification, with clinical features, imaging, and histopathological findings and a 9-year follow-up. A 16-year-old girl presented with headache, vomiting, and vertigo. Magnetic resonance imaging (MRI) demonstrated a hyperintense mass with heterogenous enhancement in the right cerebellopontine angle and internal auditory canal. No leptomeningeal involvement was seen. The histological examination revealed neoplastic tissue of moderate cellularity formed mostly by oligodendrocyte-like cells. Follow-up MRI scans demonstrated cystic lesions in the subarachnoid spaces in the brain with vivid leptomeningeal enhancement. Later spread of the tumour was found in the spinal canal. On demand biopsy samples were re-examined, and pathological diagnosis was identified as DLGNT. In contrast to most reported DLGNTs, the tumour described in this manuscript did not present with diffuse leptomeningeal spread, but later presented with leptomeningeal involvement in the brain and spinal cord. Our case expands the spectrum of radiological features, provides a long-term clinical and radiological follow-up, and highlights the major role of molecular genetic testing in unusual cases