Flunarizine as a Candidate for Drug Repurposing Against Human Pathogenic Mammarenaviruses.

Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence the significance of developing therapeutics against the mammarenavirus Lassa virus (LASV), the causative agent of LF. We used in silico docking approaches to investigate the binding affinities of 2015 existing drugs to LASV proteins known to play critical roles in the formation and activity of the virus ribonucleoprotein complex (vRNP) responsible for directing replication and transcription of the viral genome.

Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance.

The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which led the WHO to declare this mpox outbreak a public health emergency of international concern. The FDA-approved small molecule antiviral tecovirimat (TPOXX) is recommended to treat mpox cases with severe symptoms, but the limited efficacy of TPOXX and the emergence of TPOXX resistant MPXV variants has challenged this medical practice of care and highlighted the urgent need for alternative therapeutic strategies. In this study we have used vaccinia virus (VACV) as a surrogate of MPXV to assess the antiviral efficacy of combination therapy of TPOXX together with mycophenolate mofetil (MMF), an FDA-approved immunosuppressive agent that we have shown to inhibit VACV and MPXV, or the N-myristoyltransferase (NMT) inhibitor IMP-1088.

Prion protein modulation of virus-specific T cell differentiation and function during acute viral infection.

The differentiation and functionality of virus-specific T cells during acute viral infections are crucial for establishing long-term protective immunity. While numerous molecular regulators impacting T cell responses have been uncovered, the role of cellular prion proteins (PrPc) remains underexplored. Here, we investigated the impact of PrPc deficiency on the differentiation and function of virus-specific T cells using the lymphocytic choriomeningitis virus (LCMV) Armstrong acute infection model.

SMC motor proteins extrude DNA asymmetrically and can switch directions.

Structural maintenance of chromosomes (SMC) complexes organize the genome via DNA loop extrusion. Although some SMCs were reported to do so symmetrically, reeling DNA from both sides into the extruded DNA loop simultaneously, others perform loop extrusion asymmetrically toward one direction only. The mechanism underlying this variability remains unclear.

Instagram Versus Reality: Who Are Actually Plastic Surgeons?

Background: Instagram has become one of the most powerful marketing tools available to plastic surgeons because patients have increasingly turned to online resources to find physicians. Within, we review the online presence of self-ascribed plastic surgeons in the United States to identify potential misinformation and dishonest advertising.

Methods: The Inflact database was queried for the search terms: "plastic surgeon/surgery," "plastic and reconstructive surgeon/surgery," "aesthetic surgeon/surgery," and "cosmetic surgeon/surgery.