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Novel siRNA therapeutics demonstrate multi-variant efficacy against SARS-CoV-2
Antiviral Res. 2023 Jul 19:105677. doi: 10.1016/j.antiviral.2023.105677. Online ahead of print.ABSTRACTSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that causes COVID-19 disease, with an estimated global mortality of approximately 2%. While global response strategies, which are predominantly reliant on regular vaccinations, have shifted from zero COVID to living with COVID, there is a distinct lack of broad-spectrum direct acting antiviral therapies that maintain efficacy across evolving SARS-CoV-2 variants of concern. This is of most concern for immunocompromised and immunosuppressed ...
Source: Antiviral Research - July 21, 2023 Category: Virology Authors: Ellen Bowden-Reid Scott Ledger Yuan Zhang Francesca Di Giallonardo Anupriya Aggarwal Alberto Ospina Stella Anouschka Akerman Vanessa Milogiannakis Gregory Walker William Rawlinson Stuart Turville Anthony D Kelleher Chantelle Ahlenstiel Source Type: research

Numb-associated kinases are required for SARS-CoV-2 infection and are cellular targets for antiviral strategies
Antiviral Res. 2022 Jun 20;204:105367. doi: 10.1016/j.antiviral.2022.105367. Online ahead of print.ABSTRACTThe coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose serious threats to global health. We previously reported that AAK1, BIKE and GAK, members of the Numb-associated kinase family, control intracellular trafficking of multiple RNA viruses during viral entry and assembly/egress. Here, using both genetic and pharmacological approaches, we probe the functional relevance of NAKs for SARS-CoV-2 infection. siRNA-mediated depletion of AA...
Source: Antiviral Research - June 23, 2022 Category: Virology Authors: Marwah Karim Sirle Saul Luca Ghita Malaya Kumar Sahoo Chengjin Ye Nishank Bhalla Chieh Wen Lo Jing Jin Jun-Gyu Park Bel én Martinez-Gualda Michael Patrick East Gary L Johnson Benjamin A Pinsky Luis Martinez-Sobrido Christopher R M Asquith Aarthi Narayana Source Type: research

Viruses, Vol. 13, Pages 2030: Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence
Drosten Jens Kurreck Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide and led to approximately 4 million deaths as of August 2021. Despite successful vaccine development, treatment options are limited. A promising strategy to specifically target viral infections is to suppress viral replication through RNA interference (RNAi). Hence, we designed eight small interfering RNAs (siRNAs) targeting the highly conserved 5’-untranslated region (5’-UTR) of SARS-CoV-2. The most promising candidate identified in initial reporter assays, termed siCoV6, targets the ...
Source: Viruses - October 8, 2021 Category: Virology Authors: Beatrice Tolksdorf Chuanxiong Nie Daniela Niemeyer Viola R öhrs Johanna Berg Daniel Lauster Julia M. Adler Rainer Haag Jakob Trimpert Benedikt Kaufer Christian Drosten Jens Kurreck Tags: Article Source Type: research

Viruses, Vol. 13, Pages 270: Synthetic Messenger RNA-Based Vaccines: from Scorn to Hype
o In the race for a vaccine against SARS-CoV-2, the synthetic mRNA format has been shown to be the fastest one and proved to be safe and highly efficient, even at the very low dose of a few µg per injection. The mRNA vaccines are not new: vaccines that are based on attenuated mRNA viruses, such as Mumps, Measles, and Rubella, immunize by delivering their mRNAs into the cells of the vaccinated individual, who produces the viral proteins that then prime the immune response. Synthetic mRNA in liposomes can be seen as a modern, more refined, and thereby a safer version of those live attenuated RNA viruses. The anti-COVID-...
Source: Viruses - February 9, 2021 Category: Virology Authors: Steve Pascolo Tags: Review Source Type: research

Viruses, Vol. 12, Pages 924: Viral Vectors Applied for RNAi-Based Antiviral Therapy
m RNA interference (RNAi) provides the means for alternative antiviral therapy. Delivery of RNAi in the form of short interfering RNA (siRNA), short hairpin RNA (shRNA) and micro-RNA (miRNA) have demonstrated efficacy in gene silencing for therapeutic applications against viral diseases. Bioinformatics has played an important role in the design of efficient RNAi sequences targeting various pathogenic viruses. However, stability and delivery of RNAi molecules have presented serious obstacles for reaching therapeutic efficacy. For this reason, RNA modifications and formulation of nanoparticles have proven useful for non-...
Source: Viruses - August 22, 2020 Category: Virology Authors: Kenneth Lundstrom Tags: Review Source Type: research

miR-142a-3p promotes the proliferation of porcine hemagglutinating encephalomyelitis virus by targeting Rab3a
In this study, we found that PHEV infection upregulates miR-142a-3p RNA expression in N2a cells and in the CNS of mice. Downregulation of miR-142a-3p by an miRNA inhibitor led to a significant repression of viral proliferation, implying that it acts as a positive regulator of PHEV proliferation. Using a dual-luciferase reporter assay, miR-142a-3p was found to bind directly bound to the 3 ’ untranslated region (3’UTR) of Rab3a mRNA and downregulate its expression. Knockdown of Rab3a expression by transfection with an miR-142a-3p mimic or Rab3a siRNA significantly increased PHEV replication in N2a cells. Conversely, the ...
Source: Archives of Virology - December 12, 2019 Category: Virology Source Type: research

Viruses, Vol. 11, Pages 152: Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus Propagation in Cells from an Insectivorous Bat
ram Misra Insectivorous bats are speculated to be ancestral hosts of Middle-East respiratory syndrome (MERS) coronavirus (CoV). MERS-CoV causes disease in humans with thirty-five percent fatality, and has evolved proteins that counteract human antiviral responses. Since bats experimentally infected with MERS-CoV do not develop signs of disease, we tested the hypothesis that MERS-CoV would replicate less efficiently in bat cells than in human cells because of its inability to subvert antiviral responses in bat cells. We infected human and bat (Eptesicus fuscus) cells with MERS-CoV and observed that the virus grew to hig...
Source: Viruses - February 13, 2019 Category: Virology Authors: Arinjay Banerjee Darryl Falzarano Noreen Rapin Jocelyne Lew Vikram Misra Tags: Article Source Type: research

A recombinant VSV-vectored MERS-CoV vaccine induces neutralizing antibody and T cell responses in rhesus monkeys after single dose immunization
Publication date: Available online 12 December 2017 Source:Antiviral Research Author(s): Renqiang Liu, Jinliang Wang, Yu Shao, Xijun Wang, Huilei Zhang, Lei Shuai, Jinying Ge, Zhiyuan Wen, Zhigao Bu Middle East respiratory syndrome coronavirus (MERS-CoV) has been a highly threatening zoonotic pathogen since its outbreak in 2012. Similar to SARS-CoV, MERS-CoV belongs to the coronavirus family and can induce severe respiratory symptoms in humans, with an average case fatality rate of 35% according to the World Health Organization. Spike (S) protein of MERS-CoV is immunogenic and can induce neutralizing antibodies, thus is a...
Source: Antiviral Therapy - December 13, 2017 Category: Virology Source Type: research

A recombinant VSV-vectored MERS-CoV vaccine induces neutralizing antibody and T cell responses in rhesus monkeys after single dose immunization.
Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) has been a highly threatening zoonotic pathogen since its outbreak in 2012. Similar to SARS-CoV, MERS-CoV belongs to the coronavirus family and can induce severe respiratory symptoms in humans, with an average case fatality rate of 35% according to the World Health Organization. Spike (S) protein of MERS-CoV is immunogenic and can induce neutralizing antibodies, thus is a potential major target for vaccine development. Here we constructed a chimeric virus based on the vesicular stomatitis virus (VSV) in which the G gene was replaced by MERS-CoV S gen...
Source: Antiviral Research - December 12, 2017 Category: Virology Authors: Liu R, Wang J, Shao Y, Wang X, Zhang H, Shuai L, Ge J, Wen Z, Bu Z Tags: Antiviral Res Source Type: research

Viruses, Vol. 7, Pages 6689-6706: Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling
This study examined the mechanism underlying this phenomenon by measuring the expression of antiviral genes—tumor necrosis factor alpha (TNF-α) and GTPase myxovirus resistance 1 (MX1)—in G6PD-knockdown cells upon human coronavirus 229E (HCoV-229E) and enterovirus 71 (EV71) infection. Molecular analysis revealed that the promoter activities of TNF-α and MX1 were downregulated in G6PD-knockdown cells, and that the IκB degradation and DNA binding activity of NF-κB were decreased. The HSCARG protein, a nicotinamide adenine dinucleotide phosphate (NADPH) sensor and negative regulator of NF-κB, was upregulated in G6PD-k...
Source: Viruses - December 17, 2015 Category: Virology Authors: Yi-Hsuan WuDaniel ChiuHsin-Ru LinHsiang-Yu TangMei-Ling ChengHung-Yao Ho Tags: Article Source Type: research