Inhibition of coronavirus infection by a synthetic STING agonist in primary human airway system.
In this study, we investigated the anti-coronavirus activity triggered by STING activation. We discovered that dimeric amidobenzimidazole (diABZI), a synthetic small molecule STING receptor agonist, showed potent anti-coronavirus activity against both the common cold human coronavirus 229E (HCoV-229E) and SARS-CoV-2 in cell culture systems. In addition, we demonstrated that the antiviral activity of diABZI was dependent on the interferon pathway in HCoV-229E infected normal human fibroblast lung cells (MRC-5) and reconstituted primary human airway air-liquid interface (ALI) cultures. Furthermore, low-dose of diABZI treatme...
Source: Antiviral Research - January 11, 2021 Category: Virology Authors: Zhu Q, Zhang Y, Wang L, Yao X, Wu D, Cheng J, Pan X, Liu H, Yan Z, Gao L Tags: Antiviral Res Source Type: research
Broad spectrum compounds targeting early stages of RABV infection.
Abstract ABMA and its analogue DABMA are two molecules of the adamantane family known to perturbate the endosomal pathway and to inhibit cell infection by several RNA and DNA viruses. Their activity against Rabies Virus (RABV) infection has already been demonstrated in vitro. (Wu et al., 2017, 2019). Here, we describe in more details their mechanism of action by comparison to Arbidol (umifenovir) and Ribavirin, two broad spectrum antivirals against emerging viruses such as Lassa, Ebola, influenza and Hantaan viruses. ABMA and DABMA, delivered 2 h pre-infection, inhibit RABV infection in vitro with an EC50 of 7.8 &...
Source: Antiviral Research - January 11, 2021 Category: Virology Authors: Kali S, Jallet C, Azebi S, Cokelaer T, Da Fonseca JP, Wu Y, Barbier J, Cintrat JC, Gillet D, Tordo N Tags: Antiviral Res Source Type: research
First report of antiviral activity of nordihydroguaiaretic acid against Fort Sherman virus (Orthobunyavirus).
The objective of this work was to study the in vitro antiviral activity of nordihydroguaiaretic acid (NDGA), the most important active compound of Larrea divaricata Cav. (Zigophyllaceae), against Fort Sherman virus (FSV) as a model of Orthobunyavirus genus. At the same time, the effect of NDGA as a lipolytic agent on the cell cycle of this viral model was assessed. The method of reducing plaque forming units on LLC-MK2 cells was used to detect the action of NDGA on CbaAr426 and SFCrEq231 isolates of FSV. NDGA did not show virucidal effect, but it had antiviral activity with a similar inhibition in both isolates, which was ...
Source: Antiviral Research - January 11, 2021 Category: Virology Authors: Martinez F, Mugas ML, Aguilar JJ, Marioni J, Contigiani MS, Núñez Montoya SC, Konigheim BS Tags: Antiviral Res Source Type: research
Identification Of Potential Inhibitors Of Protein-Protein Interaction Useful To Fight Against Ebola And Other Highly Pathogenic Viruses.
do R, Gil C Abstract Despite the efforts to develop new treatments against Ebola virus (EBOV) there is currently no antiviral drug licensed to treat patients with Ebola virus disease (EVD). Therefore, there is still an urgent need to find new drugs to fight against EBOV. In order to do this, a virtual screening was done on the druggable interaction between the EBOV glycoprotein (GP) and the host receptor NPC1 with a subsequent selection of compounds for further validation. This screening led to the identification of new small organic molecules with potent inhibitory action against EBOV infection using lentiviral E...
Source: Antiviral Research - January 8, 2021 Category: Virology Authors: Lasala F, García-Rubia A, Requena C, Galindo I, Cuesta-Geijo MA, García-Dorival I, Bueno P, Labiod N, Luczkowiak J, Martinez A, Campillo NE, Alonso C, Delgado R, Gil C Tags: Antiviral Res Source Type: research
Identification of a novel inhibitor targeting influenza A virus group 2 hemagglutinins.
Abstract Influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are major public health concerns. The putative antiviral therapeutics are useful for the treatment of influenza, however, the emerging resistant strains necessitate a constant search for new drug candidates. Here we report the discovery of a novel antiviral agent, compound CBS1194, which was identified by a parallel high-throughput screening (HTS) campaign using two retroviral pseudotypes bearing H7 or H5 hemagglutinins (HAs). Subsequent analyses demonstrated that CBS1194 is specific to IAVs of group 2, while...
Source: Antiviral Research - January 8, 2021 Category: Virology Authors: Du R, Cheng H, Cui Q, Peet NP, Gaisina IN, Rong L Tags: Antiviral Res Source Type: research
Adefovir dipivoxil efficiently inhibits the proliferation of pseudorabies virus in vitro and in vivo.
Abstract Since 2011, highly pathogenic pseudorabies virus (PRV) variants that emerged on many farms in China have posed major economic burdens to the animal industry and have even recently caused several human cases of viral encephalitis. Currently, there are no approved effective drugs to treat PRV associated diseases in humans or pigs. Thus, it is important to develop a new effective drug for the treatment of PRV infection. To this end, we established a novel rapid method to screen drugs against PRV from 1818 kinds of small molecular drugs approved by the FDA. Using this method, we identified 21 kinds of them th...
Source: Antiviral Research - January 7, 2021 Category: Virology Authors: Wang G, Chen R, Huang P, Hong J, Cao J, Wu Q, Zheng W, Lin L, Han Q, Chen Y, Xia N Tags: Antiviral Res Source Type: research
The rocaglate CR-31-B (-) inhibits SARS-CoV-2 replication at non-cytotoxic, low nanomolar concentrations in vitro and ex vivo.
ebuhr J Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19, a severe respiratory disease with varying clinical presentations and outcomes, and responsible for a major pandemic that started in early 2020. With no vaccines or effective antiviral treatments available, the quest for novel therapeutic solutions remains an urgent priority. Rocaglates, a class of plant-derived cyclopenta[b]benzofurans, exhibit broad-spectrum antiviral activity against multiple RNA viruses including coronaviruses. Specifically, rocaglates inhibit eukaryotic initiation factor 4A (eIF4A)...
Source: Antiviral Research - January 7, 2021 Category: Virology Authors: Müller C, Obermann W, Karl N, Wendel HG, Taroncher-Oldenburg G, Pleschka S, Hartmann RK, Grünweller A, Ziebuhr J Tags: Antiviral Res Source Type: research
The effect of depot medroxyprogesterone acetate on tenofovir alafenamide in rhesus macaques.
ard C Abstract Prevention of HIV infection and unintended pregnancies are public health priorities. In sub-Saharan Africa, where HIV prevalence is highest, depot-medroxyprogesterone acetate (DMPA) is widely used as contraception. Therefore, understanding potential interactions between DMPA and antiretrovirals is critical. Here, we use a macaque model to investigate the effect of DMPA on the pharmacology of the antiretroviral tenofovir alafenamide (TAF). Female rhesus macaques received 30 mg of DMPA (n=9) or were untreated (n=9). Macaques received a human equivalent dose of TAF (1.5 mg/kg) orally by gavage. Tenofov...
Source: Antiviral Research - December 29, 2020 Category: Virology Authors: Daly MB, Sterling M, Holder A, Dinh C, Nishiura K, Khalil G, García-Lerma JG, Dobard C Tags: Antiviral Res Source Type: research
Suppression effect of plant-derived berberine on cyprinid herpesvirus 2 proliferation and its pharmacokinetics in Crucian carp (Carassius auratus gibelio).
Abstract Cyprinid herpesvirus 2 (CyHV-2), which infects silver crucian carp including goldfish (Carassius auratus auratus) and Crucian carp (Carassius auratus gibelio) with high mortality, is an emerging viral pathogen worldwide. Previous studies showed that berberine (BBR), a bioactive plant-derived alkaloid, demonstrated potential antiviral actions against many different viruses. Here, we assessed the effect of berberine hydrochloride (BBH) on the replication of CyHV-2 in vitro and in vivo. Cytotoxicity assay indicated that 5-25 μg/mL BBH was non-toxic to the RyuF-2 cells. In viral inhibition assays...
Source: Antiviral Research - December 22, 2020 Category: Virology Authors: Su M, Tang R, Wang H, Lu L Tags: Antiviral Res Source Type: research
Ponesimod suppresses hepatitis B virus infection by inhibiting endosome maturation.
Conclusion: Ponesimod is a promising anti-HBV drug targeting the endosome maturation of HBV. This finding can be applied to the development of novel antivirals that target the trafficking pathway of HBV particles. PMID: 33346055 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - December 17, 2020 Category: Virology Authors: Fauzyah Y, Ono C, Torii S, Anzai I, Suzuki R, Izumi T, Morioka Y, Maeda Y, Okamoto T, Fukuhara T, Matsuura Y Tags: Antiviral Res Source Type: research
Infectious bronchitis virus: Identification of Gallus gallus APN high-affinity ligands with antiviral effects.
In this study, Gallus gallus APN (gAPN) protein was screened by phage-displayed 12-mer peptide library. Two high-affinity peptides H (HDYLYYTFTGNP) and T (TKFSPPSFWYLH) to gAPN protein were selected for in depth characterization of their anti-IBV effects. In vitro, indirect ELISA showed that these two high-affinity ligands could bind IBV S1 antibodies. Quantitative real-time PCR (qRT-PCR) assay, virus yield reduction assay and indirect immunofluorescence assay results revealed 3.125-50 μg/ml of peptide H and 6.25-50 μg/ml of peptide T reduced IBV proliferation in chicken embryo kidney cells (CEKs). In vivo, high-affi...
Source: Antiviral Research - December 16, 2020 Category: Virology Authors: Sun X, Li L, Pan L, Wang Z, Chen H, Shao C, Yu J, Ren Y, Wang X, Huang X, Zhang R, Li G Tags: Antiviral Res Source Type: research
Isocotoin suppresses hepatitis E virus replication through inhibition of heat shock protein 90.
oss A Abstract Hepatitis E virus (HEV) causes 14 million infections and 60,000 deaths per year globally, with immunocompromised persons and pregnant women experiencing severe symptoms. Although ribavirin can be used to treat chronic hepatitis E, toxicity in pregnant patients and the emergence of resistant strains are major concerns. Therefore there is an imminent need for effective HEV antiviral agents. The aims of this study were to develop a drug screening platform and to discover novel approaches to targeting steps within the viral life cycle. We developed a screening platform for molecules inhibiting HEV repli...
Source: Antiviral Research - December 13, 2020 Category: Virology Authors: Nimgaonkar I, Archer NF, Becher I, Shahrad M, LeDesma R, Mateus A, Caballero-Gómez J, Berneshawi AR, Ding Q, Douam F, Gaska JM, Savitski MM, Kim H, Ploss A Tags: Antiviral Res Source Type: research
Effectiveness of pegylated interferon monotherapy in the treatment of chronic hepatitis D virus infection: a meta-analysis.
In conclusion, this study showed that peginterferon has limited effectiveness in HDV treatment, since only one-third of chronic HDV patients achieved viral clearance and normalized ALT levels. Morever, HBsAg clearance with seroconversion to anti-HBs has been rarely observed among chronic HDV patients. PMID: 33321155 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - December 12, 2020 Category: Virology Authors: Abdrakhman A, Ashimkhanova A, Almawi WY Tags: Antiviral Res Source Type: research
Antiviral activity against Middle East Respiratory Syndrome Coronavirus by Montelukast, an anti-asthma drug.
Abstract Middle East respiratory syndrome (MERS) is a respiratory disease caused by a coronavirus (MERS-CoV). Since its emergence in 2012, nosocomial amplifications have led to its high epidemic potential and mortality rate of 34.5 %. To date, there is an unmet need for vaccines and specific therapeutics for this disease. Available treatments are either supportive medications in use for other diseases or those lacking specificity requiring higher doses. The viral infection mode is initiated by the attachment of the viral Spike glycoprotein to the human Dipeptidyl Peptidase IV (DPP4). Our attempts to screen antivir...
Source: Antiviral Research - December 9, 2020 Category: Virology Authors: Gan HJ, Harikishore A, Lee J, Jeon S, Rajan S, Chen MW, Neo JL, Kim S, Yoon HS Tags: Antiviral Res Source Type: research
Targeting host DEAD-box RNA helicase DDX3X for treating viral infections.
Abstract DDX3X or DDX3, a member of the DEAD (asp, glu, ala, asp) box RNA helicase family of proteins, is a multifunctional protein, which is usurped by several viruses and is vital to their production. To date, 18 species of virus from 12 genera have been demonstrated to be dependent on DDX3 for virulence. In addition, DDX3 has been shown to function within 7 of 10 subcellular regions that are involved in the metabolism of viruses. As such, due to its direct interaction with viral components across most or all stages of viral life cycles, DDX3 can be considered an excellent host target for pan-antiviral drug ther...
Source: Antiviral Research - December 7, 2020 Category: Virology Authors: Winnard PT, Vesuna F, Raman V Tags: Antiviral Res Source Type: research
The NF- κB inhibitor, SC75741, is a novel antiviral against emerging tick-borne bandaviruses.
The NF-κB inhibitor, SC75741, is a novel antiviral against emerging tick-borne bandaviruses. Antiviral Res. 2020 Dec 06;:104993 Authors: Mendoza CA, Yamaoka S, Tsuda Y, Matsuno K, Weisend CM, Ebihara H Abstract Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV) cause viral hemorrhagic fever-like illnesses in humans due to an aberrant host inflammatory response, which contributes to pathogenesis. Here, we established two separate minigenome (MG) systems based on the M-segment of SFTSV and HRTV. Following characterization of both systems for SFTSV and HRTV, we use...
Source: Antiviral Research - December 6, 2020 Category: Virology Authors: Mendoza CA, Yamaoka S, Tsuda Y, Matsuno K, Weisend CM, Ebihara H Tags: Antiviral Res Source Type: research
18F-Fluorodeoxyglucose Positron Emission Tomography as a window into human dengue pathophysiology.
Abstract In mouse models of dengue virus (DENV) infection, 18F-FDG PET is able to sensitively detect tissue-specific sites of inflammation and disease activity, as well as track therapeutic response to anti- DENV agents. However, the use of 18F-FDG PET to study the pathogenesis of inflammation and disease activity in DENV infection in humans, has not been clinically validated. Here we report the 18F-FDG PET imaging results of two patients during the febrile phase of acute DENV infection, paired with serial serum viral load, NS1 and proinflammatory cytokine measurements. Our findings demonstrate that 18F-FDG PET is...
Source: Antiviral Research - December 3, 2020 Category: Virology Authors: Kalimuddin S, Xie W, Watanabe S, Tham JY, Sam H, Ki Chan KW, Yap TS, Totman JJ, Chacko AM, Vasudevan SG, Low JG Tags: Antiviral Res Source Type: research
Views on stopping nucleos(t)ide analogue therapy in patients with chronic hepatitis B.
Abstract Long-term treatment with nucleos(t)ide analogs (NAs) is the current first line therapy for patients with chronic hepatitis B (CHB), recommended by most of the current guidelines. NAs prevent disease progression, liver failure, decrease the risk of hepatocellular carcinoma (HCC), and have favorable safety profiles. However, low rates of on-therapy functional cure (hepatitis B surface antigen [HBsAg] loss), which is regarded as the optimal end point, prevent many patients from stopping NA therapy with the need for a lifelong treatment. The higher likelihood of HBsAg loss associated with stopping as compared...
Source: Antiviral Research - December 3, 2020 Category: Virology Authors: Tout I, Lampertico P, Berg T, Asselah T Tags: Antiviral Res Source Type: research
Inhibitors of APE1 Redox Function Effectively inhibit γ-herpesvirus Replication In Vitro and In Vivo.
In this study, we demonstrated that APE1 redox function is essential for Epstein-Barr virus (EBV) lytic replication as the silencing of APE1 expression or treatment with APE1 redox inhibitors C10 and E3330 can inhibit EBV lytic replication and virion production. Furthermore, C10 and E3330 also inhibit MHV-68 replication in vitro and in vivo. C10 and E3330 were able to significantly reduce the pulmonary alveolar loss and pulmonary septal enlargement in mice caused by MHV-68 infection. Altogether, (i) APE1 redox function is validated as a new antiviral target; (ii) APE1 redox inhibitors, especially C10, have potentials to be...
Source: Antiviral Research - November 30, 2020 Category: Virology Authors: Hu J, Wang Y, Yuan Y Tags: Antiviral Res Source Type: research
Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses.
This study entailed direct comparison of drug effectiveness against animal and human pathogenic viruses, namely Ebola (EBOV), African swine fever virus (ASFV), and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A panel of experimental and FDA-approved compounds targeting calcium channels and PIKfyve at the endosomal membrane caused potent reductions of entry up to 90% in SARS-CoV-2 S-protein pseudotyped retrovirus. Similar inhibition was observed against transduced EBOV glycoprotein pseudovirus and ASFV. SARS-CoV-2 infection was potently inhibited by selective estrogen receptor modulators in cells transd...
Source: Antiviral Research - November 26, 2020 Category: Virology Authors: Galindo I, Garaigorta U, Lasala F, Cuesta-Geijo MA, Bueno P, Gil C, Delgado R, Gastaminza P, Alonso C Tags: Antiviral Res Source Type: research
Metabolic regulation of the HBV-specific T cell function.
Abstract Chronically HBV infected subjects are more than 260 million worldwide; cirrhosis and liver cancer represent possible outcomes which affect around 700,000 patients per year. Both innate and adaptive immune responses are necessary for viral control and both have been shown to be defective in chronic patients. Metabolic remodeling is an essential process in T cell biology, particularly for T cell activation, differentiation and survival. Cellular metabolism relies on the conversion of nutrients into energy to support intracellular processes, and to generate fundamental intermediate components for cell prolif...
Source: Antiviral Research - November 25, 2020 Category: Virology Authors: Barili V, Boni C, Rossi M, Vecchi A, Zecca A, Penna A, Missale G, Ferrari C, Fisicaro P Tags: Antiviral Res Source Type: research
Ionophore antibiotic X-206 is a potent inhibitor of SARS-CoV-2 infection in vitro.
Abstract Pandemic spread of emerging human pathogenic viruses, such as the current SARS-CoV-2, poses both an immediate and future challenge to human health and society. Currently, effective treatment of infection with SARS-CoV-2 is limited and broad spectrum antiviral therapies to meet other emerging pandemics are absent leaving the World population largely unprotected. Here, we have identified distinct members of the family of polyether ionophore antibiotics with potent ability to inhibit SARS-CoV-2 replication and cytopathogenicity in cells. Several compounds from this class displayed more than 100-fold selectiv...
Source: Antiviral Research - November 25, 2020 Category: Virology Authors: Svenningsen EB, Thyrsted J, Blay-Cadanet J, Liu H, Lin S, Villameriel JM, Olagnier D, Idorn M, Paludan SR, Holm CK, Poulsen TB Tags: Antiviral Res Source Type: research
Host RNA quality control as a hepatitis B antiviral target.
Abstract Inhibition of the host RNA polyadenylating polymerases, PAPD5 and PAPD7 (PAPD5/7), with dihydroxyquinoline (DHQ), a small orally available, molecule, results in a rapid and selective degradation of hepatitis B virus (HBV) RNA, and hence reduction in the amounts of viral gene products. DHQ, is a first in class investigational agent and could represent an entirely new category of HBV antivirals. PAPD5 and PAPD7 are non-canonical, cell specified, polyadenylating polymerases, also called terminal nucleotidyl transferases 4B and 4A (TENT4B/A), respectively. They are involved in the degradation of poor-quality ...
Source: Antiviral Research - November 23, 2020 Category: Virology Authors: Block TM, Young JAT, Javanbakht H, Sofia MJ, Zhou T Tags: Antiviral Res Source Type: research
Advancing Marburg virus antiviral screening: Optimization of a novel T7 polymerase-independent minigenome system.
Abstract Marburg virus (MARV) is the only known pathogenic filovirus not belonging to the genus Ebolavirus. Minigenomes have proven a useful tool to study MARV, but all existing MARV minigenomes are dependent on the addition of an exogenous T7 RNA polymerase to drive minigenome expression. However, exogenous expression of a T7 polymerase is not always feasible and can act as a confounding factor in compound screening assays. We have developed an alternative minigenome that is controlled by the natively expressed RNA polymerase II. We demonstrate here the characteristics of this new system and its applicability in ...
Source: Antiviral Research - November 18, 2020 Category: Virology Authors: Vanmechelen B, Stroobants J, Vermeire K, Maes P Tags: Antiviral Res Source Type: research
A bacterial artificial chromosome (BAC)-vectored noninfectious replicon of SARS-CoV-2.
Abstract Vaccines and antiviral agents are in urgent need to stop the COVID-19 pandemic. To facilitate antiviral screening against SARS-CoV-2 without requirement for high biosafety level facility, we developed a bacterial artificial chromosome (BAC)-vectored replicon of SARS-CoV-2, nCoV-SH01 strain, in which secreted Gaussia luciferase (sGluc) was encoded in viral subgenomic mRNA as a reporter gene. The replicon was devoid of structural genes spike (S), membrane (M), and envelope (E). Upon transfection, the replicon RNA replicated in various cell lines, and was sensitive to interferon alpha (IFN-α), remdesiv...
Source: Antiviral Research - November 17, 2020 Category: Virology Authors: Zhang Y, Song W, Chen S, Yuan Z, Yi Z Tags: Antiviral Res Source Type: research
Structural characterization of the interaction between the C-terminal domain of the influenza polymerase PA subunit and an optimized small peptide inhibitor.
valinka J, Kožíšek M Abstract Influenza viruses can cause severe respiratory infections in humans, leading to nearly half a million deaths worldwide each year. Improved antiviral drugs are needed to address the threat of development of novel pandemic strains. Current therapeutic interventions target three key proteins in the viral life cycle: neuraminidase, the M2 channel and RNA-dependent-RNA polymerase. Protein-protein interactions between influenza polymerase subunits are potential new targets for drug development. Using a newly developed assay based on AlphaScreen technology, we screened a pepti...
Source: Antiviral Research - November 6, 2020 Category: Virology Authors: Hejdánek J, Radilová K, Pachl P, Hodek J, Machara A, Weber J, Řezáčová P, Konvalinka J, Kožíšek M Tags: Antiviral Res Source Type: research
HBV evolution and genetic variability: impact on prevention, treatment and development of antivirals.
Abstract Hepatitis B virus (HBV) poses a major global health burden with 260 million people being chronically infected and 890,000 dying annually from complications in the course of the infection. HBV is a small enveloped virus with a reverse-transcribed DNA genome that infects hepatocytes and can cause acute and chronic infections of the liver. HBV is endemic in humans and apes representing the prototype member of the viral family Hepadnaviridae and can be divided into 10 genotypes. Hepadnaviruses have been found in all vertebrate classes and constitute an ancient viral family that descended from non-enveloped pr...
Source: Antiviral Research - November 6, 2020 Category: Virology Authors: Glebe D, Goldmann N, Lauber C, Seitz S Tags: Antiviral Res Source Type: research
Burden of influenza B virus infection and considerations for clinical management.
Abstract Influenza B viruses cause significant morbidity and mortality, particularly in children, but the awareness of their impact is often less than influenza A viruses partly due to their lack of pandemic potential. Here, we summarise the biology, epidemiology and disease burden of influenza B, and review existing data on available antivirals for its management. There has long been uncertainty surrounding the clinical efficacy of neuraminidase inhibitors (NAIs) for influenza B treatment. In this article, we bring together the existing data on NAIs and discuss these alongside recent large randomised controlled t...
Source: Antiviral Research - November 4, 2020 Category: Virology Authors: Zaraket H, Hurt AC, Clinch B, Barr I, Lee N Tags: Antiviral Res Source Type: research
Identification of quinolone derivatives as effective anti-Dengue virus agents.
In this study, we describe two novel compounds with anti-DENV2 activity, tentatively named Compound-X and Compound-Y. Both compounds possess a quinolone skeleton, and the EC50s of Compound-X and Compound-Y against DENV2 were 3.9 μM and 9.2 μM, respectively. Based on a DENV replicon assay, it was suggested that these compounds have anti-DENV2 activity by inhibition of a step in virus replication. Furthermore, using mutational analysis we obtained compounds-resistant to DENV2 infection and identified a mutation, V130A in the NS5 methyltransferase (MTase) domain. However, these compounds did not inhibit MTase ...
Source: Antiviral Research - November 4, 2020 Category: Virology Authors: Nobori H, Uemura K, Toba S, Sanaki T, Shishido T, Hall WW, Orba Y, Sawa H, Sato A Tags: Antiviral Res Source Type: research
Development and characterization of recombinant tick-borne encephalitis virus expressing mCherry reporter protein: a new tool for high-throughput screening of antiviral compounds, and neutralizing antibody assays.
zek D Abstract The flavivirus, tick-borne encephalitis virus (TBEV) is transmitted by Ixodes spp. ticks and may cause severe and potentially lethal neurological tick-borne encephalitis (TBE) in humans. Studying TBEV requires the use of secondary methodologies to detect the virus in infected cells. To overcome this problem, we rationally designed and constructed a recombinant reporter TBEV that stably expressed the mCherry reporter protein. The resulting TBEV reporter virus (named mCherry-TBEV) and wild-type parental TBEV exhibited similar growth kinetics in cultured cells; however, the mCherry-TBEV virus produced ...
Source: Antiviral Research - November 3, 2020 Category: Virology Authors: Haviernik J, Eyer L, Yoshii K, Kobayashi S, Cerny J, Nougairède A, Driouich JS, Volf J, Palus M, de Lamballerie X, Gould EA, Ruzek D Tags: Antiviral Res Source Type: research
Drug screening identified gemcitabine inhibiting hepatitis E virus by inducing interferon-like response via activation of STAT1 phosphorylation.
In this study, a safe-in-human broad-spectrum antiviral drug library comprising of 94 agents was used. Upon screening, we identified gemcitabine, a widely used anti-cancer drug, as a potent inhibitor of HEV replication. The antiviral effect was confirmed in a range of cell culture models with genotype 1 and 3 HEV strains. As a cytidine analog, exogenous supplementation of pyrimidine nucleosides effectively reversed the antiviral activity of gemcitabine, but the level of pyrimidine nucleosides per se does not affect HEV replication. Surprisingly, similar to interferon-alpha (IFNα) treatment, gemcitabine activates STAT...
Source: Antiviral Research - October 30, 2020 Category: Virology Authors: Li Y, Li P, Li Y, Zhang R, Yu P, Ma Z, Kainov D, de Man RA, Peppelenbosch MP, Pan Q Tags: Antiviral Res Source Type: research
BIKE regulates dengue virus infection and is a cellular target for broad-spectrum antivirals.
Abstract Global health is threatened by emerging viruses, many of which lack approved therapies and effective vaccines, including dengue, Ebola, and Venezuelan equine encephalitis. We previously reported that AAK1 and GAK, two of the four members of the understudied Numb-associated kinases (NAK) family, control intracellular trafficking of RNA viruses. Nevertheless, the role of BIKE and STK16 in viral infection remained unknown. Here, we reveal a requirement for BIKE, but not STK-16, in dengue virus (DENV) infection. BIKE mediates both early (postinternalization) and late (assembly/egress) stages in the DENV life ...
Source: Antiviral Research - October 30, 2020 Category: Virology Authors: Pu S, Schor S, Karim M, Saul S, Robinson M, Kumar S, Prugar LI, Dorosky DE, Brannan J, Dye JM, Einav S Tags: Antiviral Res Source Type: research
Substitution-inert polynuclear platinum compounds inhibit human cytomegalovirus attachment and entry.
In this study, we investigated as possible antiviral agents substitution-inert cationic polynuclear platinum complexes (PPCs) that demonstrate charge-dependent high affinity for GAGs (Katner et al., 2018; Peterson et al., 2017). Certain PPCs had anti-HCMV activities in low micromolar concentrations and antiviral activity correlated with their GAG-binding affinity. Time of addition, removal, and mechanistic studies were consistent with PPCs binding to cells and blocking HCMV virion attachment; however, evidence also suggested that PPC/virion interactions could inhibit fibroblast but not epithelial cell infection. We hypothe...
Source: Antiviral Research - October 22, 2020 Category: Virology Authors: Shoup M, Ourahmane A, Ginsburg EP, Farrell NP, McVoy MA Tags: Antiviral Res Source Type: research
Safety, pharmacokinetics and pharmacodynamics of SYN023 alone or in combination with a rabies vaccine: An open, parallel, single dose, phase 1 bridging study in healthy Chinese subjects.
CONCLUSION: SYN023 at 0.3 mg/kg is relatively saf e and effective and can be selected for further clinical trials in Chinese subjects. The clinical trial registration number is CTR20190281. http://www.chinadrugtrials.org.cn/eap/clinicaltrials.searchlist?a=a®_no=CTR20190281. PMID: 33091433 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - October 19, 2020 Category: Virology Authors: Ding Y, Wu M, Zhang H, Zhu X, Hu Y, Li X, Liu J, Tsao E, Liu M, Li C Tags: Antiviral Res Source Type: research
Antiviral activity and safety of remdesivir against SARS-CoV-2 infection in human pluripotent stem cell-derived cardiomyocytes.
In this study, remdesivir exhibited up to 60-fold higher antiviral activity in hPSC-CMs compared to Vero E6 cells; however, it also induced moderate cardiotoxicity in these cells. To gain further insight into the drug-induced arrhythmogenic risk, we assessed QT interval prolongation and automaticity of remdesivir-treated hPSC-CMs using a multielectrode array (MEA). As a result, the data indicated a potential risk of QT prolongation when remdesivir is used at concentrations higher than the estimated peak plasma concentration. Therefore, we conclude that close monitoring of the electrocardiographic/QT interval should be advi...
Source: Antiviral Research - October 19, 2020 Category: Virology Authors: Choi SW, Shin JS, Park SJ, Jung E, Park YG, Lee J, Kim SJ, Park HJ, Lee JH, Park SM, Moon SH, Ban K, Go YY Tags: Antiviral Res Source Type: research
Betulinic Acid exhibits antiviral effects against dengue virus infection.
In this study, betulinic acid, a naturally occurring pentacyclic triterpenoid was established as an inhibitor of DENV infection in vitro. Time-course studies revealed that betulinic acid inhibits a post-entry stage of the DENV replication cycle and subsequent analyses also showed that the compound is able to inhibit viral RNA synthesis and protein production. Betulinic acid also demonstrated antiviral efficacy against other serotypes of DENV, as well as against other mosquito-borne RNA viruses such as Zika virus and Chikungunya virus, which are commonly found co-circulating together with DENV. As such, betulinic acid may s...
Source: Antiviral Research - October 17, 2020 Category: Virology Authors: Choy Loe MW, Hao E, Chen M, Li C, Hua Lee RC, Yu Zhu IX, Teo ZY, Chin WX, Hou X, Deng J, Hann Chu JJ Tags: Antiviral Res Source Type: research
Anti-viral effect in chronic hepatitis B patients with normal or mildly elevated alanine aminotransferase.
Abstract BACKGROUND & AIMS: Normal/mildly elevated ALT (30-years. The rate of undetectable HBV DNA in NAs and PEG-IFN groups was ∼50%, ∼80% or ∼90% at week 24, 48 or 72, respectively. HBeAg clearance rate was lower in NAs treated than that in PEG-IFN group at week 48 (6% vs 20%, P
Source: Antiviral Research - October 13, 2020 Category: Virology Authors: Zhao Q, Liu K, Zhu X, Yan L, Ding Y, Xu Y, Lou S, Zhao G, Xie Q, Gao Y, Bao S, Wang H Tags: Antiviral Res Source Type: research
Unexpected complete recovery of a patient with severe tick-borne encephalitis treated with favipiravir.
We report a case of tick-borne encephalitis (TBE) in a 22-year-old man, who was admitted to the Medical University of Vienna hospital with severe meningoencephalitis, unresponsive and dependent on a respirator. He had given a history of a recent tick bite, but because he had previously received a full course of vaccination against TBE, West Nile virus infection was suspected. Because the antiviral drug favipiravir has been reported to be active against WNV, therapy was initiated, and continued even after a diagnosis of TBE was confirmed, due to significant improvement of symptoms. Within days, the patient's symptoms resolv...
Source: Antiviral Research - October 12, 2020 Category: Virology Authors: Bologheanu R, Schubert L, Thurnher M, Schiefer J, Santonja I, Holzmann H, Österreicher Z, Tobudic S, Winkler S, Faybik P, Steininger C, Thalhammer F Tags: Antiviral Res Source Type: research
Duration of fever and symptoms in children after treatment with baloxavir marboxil and oseltamivir during the 2018-2019 season and detection of variant influenza A viruses with polymerase acidic subunit substitutions.
Abstract We conducted a prospective, multicenter, non-randomized observational study to assess the duration of fever and symptoms of influenza A/H1N1pdm09 and A/H3N2 infected children
Source: Antiviral Research - September 24, 2020 Category: Virology Authors: Saito R, Osada H, Wagatsuma K, Chon I, Sato I, Kawashima T, Saito T, Kodo N, Ono Y, Shimada Y, Phyu W, Shobugawa Y Tags: Antiviral Res Source Type: research
Diketo acids inhibit the cap-snatching endonuclease of several Bunyavirales.
Rocha-Pereira J Abstract Several fatal bunyavirus infections lack specific treatment. Here, we show that diketo acids engage a panel of bunyavirus cap-snatching endonucleases, inhibit their catalytic activity and reduce viral replication of a taxonomic representative in vitro. Specifically, the non-salt form of L-742,001 and its derivatives exhibited EC50 values between 5.6 to 6.9 μM against a recombinant BUNV-mCherry virus. Structural analysis and molecular docking simulations identified traits of both the class of chemical entities and the viral target that could help the design of novel, more potent molecule...
Source: Antiviral Research - September 23, 2020 Category: Virology Authors: Fernández-García Y, Horst ST, Bassetto M, Brancale A, Neyts J, Rogolino D, Sechi M, Carcelli M, Günther S, Rocha-Pereira J Tags: Antiviral Res Source Type: research
Generation of a reporter yellow fever virus for high throughput antiviral assays.
Abstract Yellow fever virus (YFV), a member of the Flaviviridae family, is an arthropod-borne virus that can cause severe disease in humans with a lethality rate of up to 60%. Since 2017, increases in YFV activity in areas of South America and Africa have been described. Although a vaccine is available, named strain 17D (Theiler and Smith, 1937), it is contraindicated for use in the elderly, expectant mothers, immunocompromised people, among others. To this day there is no antiviral treatment against YFV to reduce the severity of viral infection. Here, we used a circular polymerase extension reaction (CPER)-based ...
Source: Antiviral Research - September 23, 2020 Category: Virology Authors: Sanchez-Velazquez R, de Lorenzo G, Tandavanitj R, Setthapramote C, Bredenbeek PJ, Bozzacco L, MacDonald MR, Clark JJ, Rice CM, Patel AH, Kohl A, Varjak M Tags: Antiviral Res Source Type: research
Tenofovir alafenamide does not inhibit mitochondrial function and cholesterol biosynthesis in human T lymphoblastoid cell line.
In conclusion, our findings add to the emerging data that TAF may have a low potential for causing mitochondrial toxicity in HIV-infected individuals on TAF-containing regimens. PMID: 32980447 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - September 23, 2020 Category: Virology Authors: Li M, Zhou L, Dorsey HG, Musoff C, Jnr DA, Schoen N, Djan K, Paintsil E Tags: Antiviral Res Source Type: research
Immune response to varicella-zoster virus before and after renal transplantation.
Abstract BACKGROUND: Herpes zoster (HZ) risk is high in renal transplant recipients. Vaccination prior to transplantation may provide a useful strategy for the prevention of HZ in the posttranplantation period. However, it is not known whether immunity to varicella-zoster virus (VZV) is affected due to treatment surrounding transplantation. METHODS: Both humoral and cellular immunity to VZV were determined prior to and 2-3 years after renal transplantation in 60 adult patients, and 62 matched healthy controls. VZV-specific cellular immunity was measured by interferon gamma (IFNγ) enzyme-linked immunospo...
Source: Antiviral Research - September 22, 2020 Category: Virology Authors: Rondaan C, de Joode AAE, Wang L, Siderius M, Raveling-Eelsing E, van Leer C, van Assen S, Bos NA, Westra J Tags: Antiviral Res Source Type: research
Avian anti-NS1 IgY antibodies neutralize dengue virus infection and protect against lethal dengue virus challenge.
In this study, we used egg yolks from DENV-immunized geese to purify IgY antibodies specific to DENV NS1 epitopes. We determined that 2 anti-NS1 IgY antibodies, NS1-1 and NS1-8, were capable of neutralizing DENV infection in vitro. In addition, these antibodies did not cross-react with the DENV Envelope (E) protein nor enhance DENV or Zika virus (ZIKV) infection in vitro. Intriguingly, NS1-8, but not NS1-1, partially blocked NS1-induced endothelial dysfunction in vitro while neither antibody blocked binding of soluble NS1 to cells. Finally, prophylactic treatment of mice with NS1-8 conferred significant protection against ...
Source: Antiviral Research - September 22, 2020 Category: Virology Authors: O'Donnell KL, Espinosa DA, Puerta-Guardo H, Biering SB, Schiltz J, Nilles ML, Li J, Harris E, Bradley DS Tags: Antiviral Res Source Type: research
Characterization of hepatitis B virus surface antigen particles expressed in stably transformed mammalian cell lines containing the large, middle and small surface protein.
Abstract Vaccination still represents the most efficient and inexpensive strategy in the control of hepatitis B virus (HBV) infection. However, about 10 % of the population vaccinated with the current yeast derived vaccine, consisting of the non-glycosylated form of the small envelope protein (S) of the HBV, fail to display an adequate immune response. Therefore, there is a need for the development of new vaccines with enhanced immunogenicity. On this regard, new generation vaccines containing L and preS2-containing HBV surface proteins in addition to S, have proven to be able to bypass the lack of response of the...
Source: Antiviral Research - September 22, 2020 Category: Virology Authors: Battagliotti JM, Diego F, Marina E, Ricardo K, Claudio P Tags: Antiviral Res Source Type: research
Cryptotanshinone Protects Porcine Alveolar Macrophages from Infection with Porcine Reproductive and Respiratory Syndrome Virus.
We report that the natural compound cryptotanshinone (Cpt) effectively inhibits the PRRSV infection of porcine alveolar macrophages (PAMs), the primary cell target of PRRSV in vivo. Mechanistically, Cpt inhibits the activation of signal transducer and activator of transcription 3 (STAT3), and blocks the interleukin 10 (IL-10) stimulated as well as the basal level expression of CD163 in PAMs. Cpt-treatment of PAMs is effective either pre- or post-PRRSV infection, resulting in significantly inhibited PRRSV infection in a dose-dependent manner. Our study identified a new route to prevent/treat PRRSV infection of pigs by using...
Source: Antiviral Research - September 18, 2020 Category: Virology Authors: Huang C, Zhu J, Wang L, Chu A, Yin Y, Vali K, Garmendia A, Tang Y Tags: Antiviral Res Source Type: research
A synthetic STING agonist inhibits the replication of Human Parainfluenza Virus 3 and Rhinovirus 16 through distinct mechanisms.
In this study, using dimeric amidobenzimidazole (diABZI), a newly discovered synthetic small molecule STING receptor agonist with much higher potency than CDNs, we found that activation of STING elicits potent antiviral effects against parainfluenza virus type 3 (PIV3) and human rhinovirus 16 (HRV16), two representative respiratory viral pathogens. Notably, while anti-PIV3 activity was depend on the induction of type I interferon responses through TANK-binding kinase 1 (TBK1), anti-HRV16 activity required the induction of autophagy-related gene 5 (ATG5)-dependent autophagy, indicating that two distinct antiviral mechanisms...
Source: Antiviral Research - September 15, 2020 Category: Virology Authors: Zhu Q, Hu H, Liu H, Shen H, Yan Z, Gao L Tags: Antiviral Res Source Type: research
Castanospermine reduces Zika virus infection-associated seizure by inhibiting both the viral load and inflammation in mouse models.
Abstract Zika virus (ZIKV) outbreaks have been reported worldwide, including a recent occurrence in Brazil where it spread rapidly, and an association with increased cases of microcephaly was observed in addition to neurological issues such as GBS that were reported during previous outbreaks. Following infection of neuronal tissues, ZIKV can cause inflammation, which may lead to neuronal abnormalities, including seizures and paralysis. Therefore, a drug containing both anti-viral and immunosuppressive properties would be of great importance in combating ZIKV related neurological abnormalities. Castanospermine (CST...
Source: Antiviral Research - September 15, 2020 Category: Virology Authors: Tharappel AM, Cheng Y, Holmes EH, Ostrander GK, Tang H Tags: Antiviral Res Source Type: research
Vector-borne Viruses in Turkey: A Systematic Review and Bibliography.
;zkul A Abstract Turkey serves as a natural hub for the dissemination of vector-borne viruses and provides many suitable habitats with diverse ecologies for introduction and establishment of new pathogens. This manuscipt provides an updated systematic review and meta-analysis of the vector-borne viruses documented in Turkey. Following web-based identification, screening and eligibility evaluation, 291 published reports were reviewed. The publications were categorized and listed as a supplementary bibliography accompanying the manuscript. In brief, Crimean-Congo hemorrhagic fever virus (CCHFV) and West Nile virus (...
Source: Antiviral Research - September 15, 2020 Category: Virology Authors: Ergünay K, Polat C, Özkul A Tags: Antiviral Res Source Type: research
A biaryl sulfonamide derivative as a novel inhibitor of filovirus infection.
Abstract Ebolaviruses and marburgviruses, members of the family Filoviridae, are known to cause fatal diseases often associated with hemorrhagic fever. Recent outbreaks of Ebola virus disease in West African countries and the Democratic Republic of the Congo have made clear the urgent need for the development of therapeutics and vaccines against filoviruses. Using replication-incompetent vesicular stomatitis virus (VSV) pseudotyped with the Ebola virus (EBOV) envelope glycoprotein (GP), we screened a chemical compound library to obtain new drug candidates that inhibit filoviral entry into target cells. We descover...
Source: Antiviral Research - September 14, 2020 Category: Virology Authors: Isono M, Furuyama W, Kuroda M, Kondoh T, Igarashi M, Kajihara M, Yoshida R, Manzoor R, Okuya K, Miyamoto H, Feldmann H, Marzi A, Sakaitani M, Nanbo A, Takada A Tags: Antiviral Res Source Type: research