Antiviral Chemistry and Chemotherapy最新文献

{"title":"Clinical severe acute respiratory syndrome coronavirus 2 isolation and antiviral testing.","authors":"Gregory Mathez,&nbsp;Valeria Cagno","doi":"10.1177/20402066211061063","DOIUrl":"https://doi.org/10.1177/20402066211061063","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 is an RNA virus currently causing a pandemic. Due to errors during replication, mutations can occur and result in cell adaptation by the virus or in the rise of new variants. This can change the attachment receptors' usage, result in different morphology of plaques, and can affect as well antiviral development. Indeed, a molecule can be active on laboratory strains but not necessarily on circulating strains or be effective only against some viral variants. Experiments with clinical samples with limited cell adaptation should be performed to confirm the efficiency of drugs of interest. In this protocol, we present a method to culture severe acute respiratory syndrome coronavirus 2 from nasopharyngeal swabs, obtain a high viral titer while limiting cell adaptation, and assess antiviral efficiency.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"29 ","pages":"20402066211061063"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/54/bf/10.1177_20402066211061063.PMC8606911.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39645609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-influenza virus activity of the elenolic acid rich olive leaf (<i>Olea europaea</i> L.) extract Isenolic^®.","authors":"Aurora Salamanca,&nbsp;Paula Almodóvar,&nbsp;Irene Jarama,&nbsp;Daniel González-Hedström,&nbsp;Marin Prodanov,&nbsp;Antonio Manuel Inarejos-García","doi":"10.1177/20402066211063391","DOIUrl":"https://doi.org/10.1177/20402066211063391","url":null,"abstract":"<p><p>Seasonal flu is caused by influenza infection, a virus that spreads easily in human population with periodical epidemic outbreaks. The high mutational rate of influenza viruses leads to the emergence of strains resistant to the current treatments. Due to that, scientific research is focusing on the development of new anti-influenza agents as alternative or complementary treatments. Olive tree (<i>Olea europaea</i> L.) has been a source of ancestral remedies due to its antimicrobial activity. Thus, the aim of this study was to test the anti-influenza activity of a standardized olive leaf extract rich in elenolic acid (EA), Isenolic^®, compared with oseltamivir. Isenolic^® extract was characterized by High Performance Liquid Chromatography (HPLC)-Mass Spectrometry and its content in EA was determined by HPLC. Cytotoxicity, viral neuraminidase inhibitor activity and cell viability protection against influenza infection of Isenolic^® were tested <i>in vitro</i> using sialic acid overexpressing Madin-Darby Canine Kidney cells. Isenolic^® formulations showed a 4% and 8% dry basis. Oseltamivir and Isenolic^® extracts showed anti-influenza activity. The 8% Isenolic^® formulation showed a dose-dependent neuraminidase inhibitor activity higher than the 4% formulation, and preserved cell viability under viral infection. Thus, Isenolic^® become a promising natural alternative to existing influenza treatments.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"29 ","pages":"20402066211063391"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8f/c6/10.1177_20402066211063391.PMC8641117.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39926163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the anti-norovirus activity in cell culture using the mouse norovirus: Early mechanistic studies.","authors":"Jana Van Dycke,&nbsp;Jasper Rymenants,&nbsp;Johan Neyts,&nbsp;Joana Rocha-Pereira","doi":"10.1177/20402066211025175","DOIUrl":"https://doi.org/10.1177/20402066211025175","url":null,"abstract":"<p><p>Human norovirus is the main cause of viral gastroenteritis, resulting annually in ∼ 700 million infections and 200,000 deaths, of whom most are children <5 years. Mouse norovirus-infected macrophages are the most widely used <i>in vitro</i> system to screen and characterize the antiviral effect of norovirus-targeting small molecules. We have previously established antiviral assays using this system, identified novel inhibitors and performed additional studies in order to have a first insight into their mechanism of action. After the identification of novel small molecules with anti-norovirus activity (part 1 of this protocol), we here describe the logical next step which entails the generation of early information of their mode of action. This information together with a continuous improvement of the potency of compounds will contribute to the optimization of a compound class towards in vivo efficacy and a successful preclinical development.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"29 ","pages":"20402066211025175"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/79/83/10.1177_20402066211025175.PMC8450984.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39421715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Killing HIV-infected resting central memory CD4⁺ T cells by targeting inhibitor of apoptosis proteins-inhibited autophagy.","authors":"Gang Zhang, Xing Huang","doi":"10.1177/2040206620980888","DOIUrl":"10.1177/2040206620980888","url":null,"abstract":"<p><p>Dysfunction of CD4⁺ T cells by HIV infection can cause serious immune defects. Recently, Campbell and colleagues described an intriguing and simple therapeutic method for HIV-infected resting central memory CD4⁺ T cells (HIV-T_CM), dependently on inhibitor of apoptosis (IAP) family proteins-targeted and second mitochondria-derived activator of caspases (SMAC) mimetics-mediated apoptosis, which is only triggered in HIV-T_CM and not uninfected ones. Autophagy induction and subsequent formation of a ripoptosome-like death signaling complex were observed after such treatment, which may partially explain the potential mechanism. However, the direct intracellular inhibitory effects of IAPs on autophagy, as well as the critical roles of autophagy in activating extracellular anti-infection immune responses, warrant further investigation. Thus, this pointer aims to provide potential alternative mechanisms and to suggest important avenues for follow-up study.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"29 ","pages":"2040206620980888"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/41/74/10.1177_2040206620980888.PMC7876937.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25346372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the anti-norovirus activity in cell culture using the mouse norovirus: Identification of active compounds.","authors":"Jana Van Dycke, Jasper Rymenants, Johan Neyts, Joana Rocha-Pereira","doi":"10.1177/20402066211026852","DOIUrl":"10.1177/20402066211026852","url":null,"abstract":"<p><p>Human norovirus is the main cause of viral gastroenteritis, resulting annually in ∼ 700 million infections and 200,000 deaths, of whom most are children <5 years. Mouse norovirus-infected macrophages are the most widely used <i>in vitro</i> system to screen and characterize the antiviral effect of norovirus-targeting small molecules. We have previously established antiviral assays using this system, identified novel inhibitors and performed additional studies in order to have a first insight into their mechanism of action. As potent and safe anti-norovirus small molecules are urgently needed, we here describe the detailed protocol for a set of assays that will allow the identification of novel norovirus inhibitors.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"29 ","pages":"20402066211026852"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/1b/10.1177_20402066211026852.PMC8256251.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39120064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening and in vitro antiviral assessment of small molecules against fluorescent protein-expressing Bunyamwera virus in a cell-based assay using high-content imaging.","authors":"Sebastiaan Ter Horst,&nbsp;Winston Chiu,&nbsp;Johan Neyts,&nbsp;Joana Rocha-Pereira","doi":"10.1177/20402066211033478","DOIUrl":"https://doi.org/10.1177/20402066211033478","url":null,"abstract":"<p><p>Many species of the order <i>Bunyavirales</i> contain potentially fatal viruses that lack effective medical countermeasures and are therefore collectively a major public health threat. Here, we describe a cell-based assay using Bunyamwera virus (BUNV)-mCherry to identify and characterize new antiviral molecules against bunyaviruses. BUNV is the type species for the genus <i>Orthobunyavirus</i> and has been reported to cause mild symptoms in humans, such as fever, joint pain, and rash. One major benefit of using our fluorescence-based assay over classical CPE-based assays is the fact that the antiviral effect of the tested compounds and their effect on the cell viability can be determined within the same assay well. For that reason, this type of assay could significantly advance our preclinical efforts towards finding new antiviral molecules against bunyaviruses.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"29 ","pages":"20402066211033478"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/49/e3/10.1177_20402066211033478.PMC8361537.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39310277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into bioinformatic approaches for repurposing compounds as anti-viral drugs.","authors":"Wenxiao Zheng, Leonardo D'Aiuto, Matthew J Demers, Vaishali Muralidaran, Joel A Wood, Maribeth Wesesky, Ansuman Chattopadhyay, Vishwajit L Nimgaonkar","doi":"10.1177/20402066211036822","DOIUrl":"10.1177/20402066211036822","url":null,"abstract":"<p><strong>Background: </strong>Drug repurposing is a cost-effective strategy to identify drugs with novel effects. We searched for drugs exhibiting inhibitory activity to Herpes Simplex virus 1 (HSV-1). Our strategy utilized gene expression data generated from HSV-1-infected cell cultures which was paired with drug effects on gene expression. Gene expression data from HSV-1 infected and uninfected neurons were analyzed using BaseSpace Correlation Engine (Illumina®). Based on the general Signature Reversing Principle (SRP), we hypothesized that the effects of candidate antiviral drugs on gene expression would be diametrically opposite (negatively correlated) to those effects induced by HSV-1 infection.</p><p><strong>Results: </strong>We initially identified compounds capable of inducing changes in gene expression opposite to those which were consequent to HSV-1 infection. The most promising negatively correlated drugs (Valproic acid, Vorinostat) did not significantly inhibit HSV-1 infection further in African green monkey kidney epithelial cells (Vero cells). Next, we tested Sulforaphane and Menadione which showed effects similar to those caused by viral infections (positively correlated). Intriguingly, Sulforaphane caused a modest but significant inhibition of HSV-1 infection in Vero cells (IC50 = 180.4 µM, <i>p</i> = 0.008), but exhibited toxicity when further explored in human neuronal progenitor cells (NPCs) derived from induced pluripotent stem cells.</p><p><strong>Conclusions: </strong>These results reveal the limits of the commonly used SRP strategy when applied to the identification of novel antiviral drugs and highlight the necessity to refine the SRP strategy to increase its utility.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"29 ","pages":"20402066211036822"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bd/7f/10.1177_20402066211036822.PMC8411619.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39372021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical evidences on the antiviral properties of macrolide antibiotics in the COVID-19 era and beyond.","authors":"Dimitri Poddighe,&nbsp;Mohamad Aljofan","doi":"10.1177/2040206620961712","DOIUrl":"https://doi.org/10.1177/2040206620961712","url":null,"abstract":"<p><p>Macrolides are a large group of antibiotics characterised by the presence of a macro-lactone ring of variable size. The prototype of macrolide antibiotics, erythromycin was first produced by <i>Streptomyces</i> and associated species more than half a century ago; other related drugs were developed. These drugs have been shown to have several pharmacological properties: in addition to their antibiotic activity, they possess some anti-inflammatory properties and have been also considered against non-bacterial infections. In this review, we analysed the available clinical evidences regarding the potential anti-viral activity of macrolides, by focusing on erythromycin, clarithromycin and azithromycin. Overall, there is no significant evidences so far that macrolides might have a direct benefit on most of viral infections considered in this review (RSV, Influenza, coronaviruses, Ebola and Zika viruses). However, their clinical benefit cannot be ruled out without further and focused clinical studies. Macrolides may improve the clinical course of viral respiratory infections somehow, at least through indirect mechanisms relying on some and variable anti-inflammatory and/or immunomodulatory effects, in addition to their well-known antibacterial activity.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"28 ","pages":"2040206620961712"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206620961712","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38418853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small molecule antivirals - Still our best hope for a cure.","authors":"Katherine Seley-Radtke","doi":"10.1177/2040206620963964","DOIUrl":"https://doi.org/10.1177/2040206620963964","url":null,"abstract":"The non-stop daily coverage of the global race for a vaccine would lead one to believe that it is only a matter of time until one or more of the 321 vaccines being developed will be available to solve the SARSCoV-2/COVID-19 crisis. Many of us are of a different opinion. There is no guarantee that an effective vaccine will be discovered, much less available in the quantities needed to vaccinate the entire world in a timely manner. Many of us are of the opinion that a directacting antiviral, or even more likely, a cocktail of direct-acting antivirals, will transform COVID-19 from a potential death sentence to an easily treatable, mild infection that can be properly managed with minimal disruption. Vaccine development has been notoriously unpredictable. Despite decades of research, there is still no vaccine to prevent many serious viruses such as HIV/ AIDS, dengue, Zika, or norovirus (the “cruise ship” virus), among many others. Even vaccines that are available have limitations the annual flu shot is often rendered ineffective because of viral mutations and the numerous strains that circulate each year. Moreover, vaccines are not particularly stable, they require critical infrastructure and human know-how from production to application, and they take a long time to develop, even under accelerated conditions. Most antivirals can be orally self-administered, are stable, and typically straightforward to make. In addition, the immunocompromised, those with underlying health conditions, or who are allergic to the vaccine components cannot get a vaccine. Thus, even if a vaccine is developed, many people will not be able to take it, thus leaving them vulnerable to infection. Antivirals have been highly successful against many viruses; i.e, the numerous drug cocktails developed for HIV/AIDS and HCV are so effective that HIV can remain at undetectable levels for a patient’s entire lifetime, and HCV is now cured in a few weeks in 98% of infected patients. There are currently >20 FDA-approved cocktails available to treat HIV/AIDS that include 2–4 direct-acting drugs. This approach has been highly successful because it is difficult to completely shut down viral replication with only one drug, and because of this, resistance is selected for. As a result, most indications require two or more drugs to successfully reduce the selection for resistance. While the search for a cure continues, there remain concerns among many that just too much attention and funding is focused on vaccines, while ignoring small molecule antivirals. We find ourselves scrambling for a cure today because many funding agencies considered the two previous CoV outbreaks (SARS and MERS) as isolated events unlikely to affect many. As a result, funding for research on CoV antivirals was scarce at best. Clearly that consideration has proven incorrect, and one can argue that it was a fatal mistake for those we’ve lost. As we all work to find answers to this deadly pandemic, it is important not to ","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"28 ","pages":"2040206620963964"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206620963964","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38572359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world single-center experience with direct-acting antivirals for improvement of the liver fibrosis after chronic hepatitis C treatment.","authors":"Sun Hee Lee,&nbsp;Hyun Phil Shin,&nbsp;Joung Il Lee","doi":"10.1177/2040206620974835","DOIUrl":"https://doi.org/10.1177/2040206620974835","url":null,"abstract":"<p><strong>Background: </strong>Recently, new direct-acting antivirals (DAAs) are known to eradicate chronic hepatitis C (CHC) virus infection and prevent the progression of liver fibrosis. Liver fibrosis may predispose to liver cirrhosis or hepatocellular carcinoma. We investigated the effect of DAAs on liver fibrosis using non-invasive methods, and evaluated the correlations of these methods.</p><p><strong>Methods: </strong>We retrospectively analyzed 68 patients with CHC who were treated with DAAs and reached sustained virologic response at 12 weeks post-treatment from January 2016 to October 2018. The degree of liver fibrosis was assessed using serum biomarkers, such as AST-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. Liver stiffness was assessed using two-dimensional shear-wave elastography (2 D-SWE). The pre- and post-treatment serum biomarker levels and SWE findings were evaluated and compared.</p><p><strong>Results: </strong>A total of 68 patients with CHC were enrolled. The median age was 58 years (52.3-73 years) and 37 patients (54.4%) were female. After treatment, the median APRI was decreased from 0.701 to 0.328 (P < 0.0001), and the median FIB-4 was decreased from 2.355 to 1.860 (P < 0.0001). The median kPa in 2 D-SWE significantly reduced from 6.85 to 5.66 (P = 0.013). APRI and FIB-4 were significantly correlated pre- and post-treatment; however, the correlation between the serum biomarkers and 2 D-SWE was partially significant.</p><p><strong>Conclusion: </strong>The serum fibrosis biomarkers and liver stiffness on 2 D-SWE were shown to be improved after the treatment with DAAs. Further research including larger number of patients is needed to compare the efficacy of each evaluating method.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"28 ","pages":"2040206620974835"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206620974835","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38623898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}