Machine learning on large scale perturbation screens for SARS-CoV-2 host factors identifies β-catenin/CBP inhibitor PRI-724 as a potent antiviral.

Expanding antiviral treatment options against SARS-CoV-2 remains crucial as the virus evolves under selection pressure which already led to the emergence of several drug resistant strains. Broad spectrum host-directed antivirals (HDA) are promising therapeutic options, however the robust identification of relevant host factors by CRISPR/Cas9 or RNA interference screens remains challenging due to low consistency in the resulting hits. To address this issue, we employed machine learning, based on experimental data from several knockout screens and a drug screen.

Pathogenetic mechanisms and therapeutic approaches of acute-to-chronic liver failure.

Liver cirrhosis is the end stage of all chronic liver diseases and contributes significantly to overall mortality of 2% globally. The age-standardized mortality from liver cirrhosis in Europe is between 10 and 20% and can be explained by not only the development of liver cancer but also the acute deterioration in the patient's overall condition. The development of complications including accumulation of fluid in the abdomen (ascites), bleeding in the gastrointestinal tract (variceal bleeding), bacterial infections, or a decrease in brain function (hepatic encephalopathy) define an acute decompensation that requires therapy and often leads to acute-on-chronic liver failure (ACLF) by different precipitating events.

Limited neutralisation of the SARS-CoV-2 Omicron subvariants BA.1 and BA.2 by convalescent and vaccine serum and monoclonal antibodies.

Background: In recent months, Omicron variants of SARS-CoV-2 have become dominant in many regions of the world, and case numbers with Omicron subvariants BA.1 and BA.2 continue to increase.

Low But Recoverable Markers of Humoral Immune Response to BNT162b2 in Elderly LTCF Residents Five to Seven Months After Two-Dose Vaccination.

The immune response is known to wane after vaccination with BNT162b2, but the role of age, morbidity and body composition is not well understood. We conducted a cross-sectional study in long-term care facilities (LTCFs) for the elderly. All study participants had completed two-dose vaccination with BNT162b2 five to 7 months before sample collection.

Antibody-Mediated Neutralization of Authentic SARS-CoV-2 B.1.617 Variants Harboring L452R and T478K/E484Q.

The capacity of convalescent and vaccine-elicited sera and monoclonal antibodies (mAb) to neutralize SARS-CoV-2 variants is currently of high relevance to assess the protection against infections. We performed a cell culture-based neutralization assay focusing on authentic SARS-CoV-2 variants B.1.

Generation of a Sleeping Beauty Transposon-Based Cellular System for Rapid and Sensitive Screening for Compounds and Cellular Factors Limiting SARS-CoV-2 Replication.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the acute respiratory disease COVID-19, which has become a global concern due to its rapid spread. The common methods to monitor and quantitate SARS-CoV-2 infectivity in cell culture are so far time-consuming and labor-intensive. Using the Sleeping Beauty transposase system, we generated a robust and versatile cellular infection model that allows SARS-CoV-2 infection experiments compatible for high-throughput and live cell imaging.

Pediatrics and COVID-19.

Viral respiratory tract infections are prevalent in children. They have substantial effects on childhood morbidity throughout the world, especially in developing countries. In this chapter, we describe the preliminary characteristics of pediatric COVID-19 and discover that severe and critical disease in children is rare.

Surveillance of SARS-CoV-2 in Frankfurt am Main from October to December 2020 Reveals High Viral Diversity Including Spike Mutation N501Y in B.1.1.70 and B.1.1.7.

Background: International travel is a major driver of the introduction and spread of SARS-CoV-2.

Aim: To investigate SARS-CoV-2 genetic diversity in the region of a major transport hub in Germany, we characterized the viral sequence diversity of the SARS-CoV-2 variants circulating in Frankfurt am Main, the city with the largest airport in Germany, from the end of October to the end of December 2020.

Methods: In total, we recovered 136 SARS-CoV-2 genomes from nasopharyngeal swab samples.

The Comparative Clinical Performance of Four SARS-CoV-2 Rapid Antigen Tests and Their Correlation to Infectivity In Vitro.

Due to globally rising numbers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, resources for real-time reverse-transcription polymerase chain reaction (rRT-PCR)-based testing have been exhausted. In order to meet the demands of testing and reduce transmission, SARS-CoV-2 antigen-detecting rapid diagnostic tests (Ag-RDTs) are being considered. These tests are fast, inexpensive, and simple to use, but whether they detect potentially infectious cases has not been well studied.

Evaluation of a SARS-CoV-2 rapid antigen test: Potential to help reduce community spread?

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread from symptomatic patients with COVID-19, but also from asymptomatic individuals. Therefore, robust surveillance and timely interventions are essential for the control of virus spread within the community. In this regard the frequency of testing and speed of reporting, but not the test sensitivity alone, play a crucial role.

Merkel Cell Polyomavirus Encodes Circular RNAs (circRNAs) Enabling a Dynamic circRNA/microRNA/mRNA Regulatory Network.

Viral noncoding RNAs have acquired increasing prominence as important regulators of infection and mediators of pathogenesis. Circular RNAs (circRNAs) generated by backsplicing events have been identified in several oncogenic human DNA viruses. Here, we show that Merkel cell polyomavirus (MCV), the etiologic cause of ∼80% of Merkel cell carcinomas (MCCs), also expresses circular RNAs.

Proteomic approach to discover human cancer viruses from formalin-fixed tissues.

The challenge of discovering a completely new human tumor virus of unknown phylogeny or sequence depends on detecting viral molecules and differentiating them from host molecules in the virus-associated neoplasm. We developed differential peptide subtraction (DPS) using differential mass spectrometry (dMS) followed by targeted analysis to facilitate this discovery. We validated this approach by analyzing Merkel cell carcinoma (MCC), an aggressive human neoplasm, in which ~80% of cases are caused by the human Merkel cell polyomavirus (MCV).

Optimized qRT-PCR Approach for the Detection of Intra- and Extra-Cellular SARS-CoV-2 RNAs.

The novel coronavirus SARS-CoV-2 is the causative agent of the acute respiratory disease COVID-19, which has become a global concern due to its rapid spread. Meanwhile, increased demand for testing has led to a shortage of reagents and supplies and compromised the performance of diagnostic laboratories in many countries. Both the World Health Organization (WHO) and the Center for Disease Control and Prevention (CDC) recommend multi-step RT-PCR assays using multiple primer and probe pairs, which might complicate the interpretation of the test results, especially for borderline cases.

Kaposi's Sarcoma-Associated Herpesvirus-Encoded circRNAs Are Expressed in Infected Tumor Tissues and Are Incorporated into Virions.

Kaposi's sarcoma-associated herpesvirus (KSHV) has recently been found to generate circular RNAs (circRNAs) from several KSHV genes, most abundantly from K10 (viral interferon regulatory factor 4 [vIRF4]), K7.3, and polyadenylated nuclear (PAN) RNA. To define expression of these circRNAs, KSHV-infected cell lines, patient tissues, and purified virions were examined.

Circular DNA tumor viruses make circular RNAs.

Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) cause ∼2% of all human cancers. RNase R-resistant RNA sequencing revealed that both gammaherpesviruses encode multiple, uniquely stable, circular RNAs (circRNA). EBV abundantly expressed both exon-only and exon-intron circRNAs from the BamHI A rightward transcript (BART) locus (circBARTs) formed from a spliced BART transcript and excluding the EBV miRNA region.

Characterization of a Merkel Cell Polyomavirus-Positive Merkel Cell Carcinoma Cell Line CVG-1.

Merkel cell polyomavirus (MCV) plays a causal role in ∼80% of Merkel cell carcinomas (MCC). MCV is clonally integrated into the MCC tumor genome, which results in persistent expression of large T (LT) and small T (sT) antigen oncoproteins encoded by the early locus. In MCV-positive MCC tumors, LT is truncated by premature stop codons or deletions that lead to loss of the C-terminal origin binding (OBD) and helicase domains important for replication.

Treatment of human polyomavirus-7-associated rash and pruritus with topical cidofovir in a lung transplant patient: Case report and literature review.

Human polyomavirus-7-associated rash and pruritus (PVARP) is a chronic superficial viral skin infection, which primarily impacts immunocompromised individuals. We report on a case of PVARP in a lung transplant recipient. Our patient developed symptoms 13 years after being on his immunosuppressive regimen, with an insidious course of progressive gray lichenification with marked islands of sparing and quality of life-altering pruritus.