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Isoflavone agonists of IRF-3 dependent signaling have antiviral activity against RNA viruses.

There is a growing need for novel antiviral therapies that are broad spectrum, effective, and not subject to resistance due to viral mutations. Using high-throughput screening methods, including computational docking studies and an interferon-stimulated gene 54 (ISG54)-luciferase reporter assay, we identified a class of isoflavone compounds that act as specific agonists of innate immune signaling pathways and cause activation of the interferon regulatory factor (IRF-3) transcription factor. The isoflavone compounds activated the ISG54 promoter, mediated nuclear translocation of IRF-3, and disp

Status presens of antiviral drugs and strategies: Part II: RNA VIRUSES (EXCEPT RETROVIRUSES).

More than 40 compounds have been formally licensed for clinical use as antiviral drugs, and half of these are used for the treatment of HIV infections. The others have been approved for the therapy of herpesvirus (HSV, VZV, CMV), hepadnavirus (HBV), hepacivirus (HCV) and myxovirus (influenza, RSV) infections. New compounds are in clinical development or under preclinical evaluation, and, again, half of these are targeting HIV infections. Yet, quite a number of important viral pathogens (i.e. HPV, HCV, hemorrhagic fever viruses) remain in need of effective and/or improved antiviral therapies.

An integrative meta-analysis of SARS-CoV-2 RNA-protein interactomes identifies conserved host factors shared with other RNA viruses.

RNA viruses cause substantial global disease burden and depend on host RNA-binding proteins and translation machinery. However, it remains unclear which host factors are robustly engaged across independent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA interactome studies and to what extent these factors are shared with other RNA viruses. Here, we perform an integrative meta-analysis of eight published SARS-CoV-2 RNA-protein interactomes and compare them with corresponding Influenza A virus, Zika virus, and Dengue virus datasets to define conserved host networks and prioritiz…

Inhibition of RNA splicing is a novel therapeutic strategy for disruption of nuclear replicating viruses.

RNA splicing is a fundamental feature of eukaryotic gene expression that is co-opted by many nuclear-replicating viruses to produce viral tr … influenza A, which both rely on host-dependent RNA processing strategies. In contrast, cytoplasmic RNA viruses lacking spliceosome dependence were unaffected, supporting an on-target mechanism. Together, these findings identify viral RNA processing complexity as a determinant of antiviral sensitivity and establish host spliceosome dependence as a shared and …

Amplification-free Detection of Zoonotic Viruses Using Cas13 and Multiple CRISPR RNAs.

Zoonotic viruses such as hantaviruses and influenza A viruses present a threat to humans and livestock. There is thus a need for methods that are rapid, sensitive, and relatively cheap to detect infections with these pathogens early. Here we use an amplification-free CRISPR-Cas13-based assay, which is simple, cheap and field-deployable, to detect the presence or absence of genomic hantavirus or influenza A virus RNA. In addition, we evaluate whether the use of multiple CRISPR RNAs (crRNAs) can improve the sensitivity of this amplification-free method. We demonstrate that for the hantaviruses T

Recapitulating Trafficking of Nucleosides Into the Active Site of Polymerases of RNA Viruses: The Challenge and the Prize.

Nucleoside analogs are very effective antiviral agents with currently over 25 compounds approved for the therapy of viral infections. Still, their successful use against RNA viruses is very recent, despite RNA viruses comprising some of the most damaging human pathogens (e.g., Coronaviruses, Influenza viruses, or Flaviviridae such as dengue, Zika and hepatitis C viruses). The breakthrough came in 2013-2014, when the nucleoside analog Sofosbuvir became one of the cornerstones of current curative treatments for hepatitis C virus (HCV). An analog designed on the same principles, Remdesivir, has b…

Implications of RNA Viruses in the Male Reproductive Tract: An Outlook on SARS-CoV-2.

Emerging viral infections continuously pose a threat to human wellbeing. Several RNA viruses have managed to establish access to the male reproductive tract and persist in human semen. The sexual transmission of the virus is of critical public concern. The epidemiological inferences are essential to understand its complexity, particularly the probability of viral transmission from asymptomatic patients or those in the incubation period or from the patient who was previously infected and now fully recovered. From the clinical perspective, negative impacts in the male reproductive tract associat…

Interaction of RNA viruses of the natural virome with the African malaria vector, Anopheles coluzzii.

Mosquitoes are colonized by a little-studied natural virome. Like the bacterial microbiome, the virome also probably influences the biology and immunity of mosquito vector populations, but tractable experimental models are lacking. We recently discovered two novel viruses in the virome of wild Anopheles and in colonies of the malaria vector Anopheles coluzzii: Anopheles C virus and Anopheles cypovirus. Here, we describe biological interactions between these two viruses and An. coluzzii mosquitoes. Viral abundance varies reproducibly during mosquito development. DNA forms of these viruses were

Изучение роли ГБФ1 в репликации вирусов РНК с положительными свойствами.

GBF1 стал одним из факторов, требующихся для воспроизведения вирусов РНК различных семей с положительными свойствами, но его механизм действий до сих пор не известен. GBF1 — коэффициент обмена гунанина нуклеотида для членов семьи Арфа. Недавно мы определили Arf4 и Arf5 (класс II Arfs) в качестве принимающих факторов, необходимых для репликации вируса гепатита С (HCV), вируса, зависящего от GBF1. Для оценки того, сохраняется ли траектория GBF1/класса II Arf среди вирусов РНК с положительной структурой, мы изучили вирус желтой лихорадки (YFV), вирус синдбиса (SINV), коксакевирус B4 (CVB4) и коро

Совпадение в аннотации оригинала
GBF1 has emerged as a host factor required for the replication of positive-sense single-stranded RNA viruses of different families, but its mechanism of action is still unknown. GBF1 is a guanine nucleotide exchange factor for Arf family members. Recently, we identified Arf4 and Arf5 (class II Arfs) as host factors required for the replication of hepatitis C…

RNA viruses at the forefront of human infections - HIV, hepatitis C, and now Ebola.

AIDS emerged in 1981, breaking a period of proud medical progresses in controlling infectious diseases with antimicrobials and vaccines. In an unprecedented way, HIV has attracted much attention for three decades, driving the discovery of new extraordinary molecular diagnostic tools and antiviral drugs. As a result, advances in antiretroviral therapy have made it possible to change HIV infection into a chronic illness. However, the prospects for HIV eradication in the short term are not envisioned for the more than 35 million people worldwide estimated to be living with HIV.

Development of multiplex PCR for simultaneous detection of six swine DNA and RNA viruses.

Uniplex and multiplex reverse transcription-polymerase chain reaction (RT-PCR) and PCR protocols were developed and evaluated subsequently for its effectiveness in detecting simultaneously single and mixed infections in swine. Specific primers for three DNA viruses and three RNA viruses, including classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), Japanese encephalitis virus (JEV), porcine circovirus type 2 (PCV2), porcine pseudorabies virus (PRV) and porcine parvovirus (PPV) were used for testing procedure. A single nucleic acid extraction protoco…

How infections with non-retroviral RNA viruses may be involved in the development of neoplasia.

There have been reports of associations of infections with non-retroviral RNA viruses and tumour development. A hypothesis is proposed as to how non-retroviral RNA viruses may play a role in the development of neoplasia. It is based on a recent report of the detection of complementary DNA (cDNA) of the RNA virus lymphocytic choriomeningitis virus in mouse and hamster cells. This lends credence to the claim made in 1975 of the detection of cDNA copies of genomic DNA of three non-retroviral RNA viruses integrated into the DNA of host cells. Briefly, the hypothesis proposes that at least one cDNA…

Myoferlin is a component of late-stage vRNP trafficking vesicles for enveloped RNA viruses.

The Rab11 endosomal recycling pathway is exploited by important respiratory RNA viruses such as IAV and RSV, aiding viral egress from the apical surface of polarized epithelial cells. Late in infection, Rab11-containing vesicles specifically transport viral ribonucleoprotein (vRNP) complexes towards the cell surface before packaging and budding. Rather than employing traditional Rab11-positive recycling endosomes, virus-infected cells generate remodelled Rab11-containing vesicles, as observed during IAV infection. Besides Rab11, no other conserved host co-factors have been identified among the…

Methods to Characterize Mutant Spectra of RNA Viruses: The Case of SARS-CoV-2.

Viral isolates consist of complex mixtures of many variants that are termed mutant spectra, distributions, clouds or swarms. They include information on virus behavior that is not captured by consensus sequences. Here, we describe experimental procedures, a bioinformatics pipeline, and calculations to characterize the mutant spectrum of RNA viruses. The data are obtained through the high-resolution MiSeq Illumina ultra-deep sequencing platform. We describe protocols for SARS-CoV-2 patients' isolates and laboratory populations, which can be adapted to other RNA viral pathogens. Precautions for …

Amplification-free detection of zoonotic viruses using Cas13 and multiple CRISPR RNAs.

Zoonotic viruses such as hantaviruses and influenza A viruses present a threat to humans and livestock. There is thus a need for methods that are rapid, sensitive and relatively cheap to detect infections with these pathogens early. Here, we use an amplification-free clustered regularly interspaced short palindromic repeats-associated protein 13 (CRISPR-Cas13)-based assay, which is simple, cheap and field-deployable, to detect the presence or absence of genomic hantavirus or influenza A virus RNA. In addition, we evaluate whether the use of multiple CRISPR RNAs (crRNAs) can improve the sensiti

Metatranscriptomic analysis reveals the diversity of RNA viruses in ticks in Inner Mongolia, China.

BACKGROUND: Ticks are widely distributed throughout China and are the second most prevalent pathogen vectors in the world, following only mo … plication of polymerase chain reaction (PCR) paired with Sanger sequencing. RESULTS: A total of 20 RNA viruses belonging to at least 8 families, including Chuviridae, Flaviviridae, Solemoviridae, Nairoviridae, Partitiviridae, Phenuiviridae, Rhabdoviridae, and Totiviridae, and to unclassified families were identified by NGS. Five of the identified RNA viruses …

RNA Viruses of Amblyomma variegatum and Rhipicephalus microplus and Cattle Susceptibility in the French Antilles.

Ticks transmit a wide variety of pathogens including bacteria, parasites and viruses. Over the last decade, numerous novel viruses have been described in arthropods, including ticks, and their characterization has provided new insights into RNA virus diversity and evolution. However, little is known about their ability to infect vertebrates. As very few studies have described the diversity of viruses present in ticks from the Caribbean, we implemented an RNA-sequencing approach on Amblyomma variegatum and Rhipicephalus microplus ticks collected from cattle in Guadeloupe and Martinique. Among t

Antiviral activity of aspirin against RNA viruses of the respiratory tract-an in vitro study.

AIM: Aspirin (acetylsalicylic acid) has been used for more than 115 years in medicine. Research exists to show that aspirin has antiviral ef … highly effective against influenza A H1N1 virus. The antiviral activity against further respiratory RNA viruses was less distinct. Respiratory syncytial virus was minimally inhibited. However, the activity of aspirin against rhinoviruses was more pronounced. Aspirin demonstrated antiviral activity against all human rhinoviruses (HRV), but the effect on member …