scholarly journals Antiviral Compounds from Myxobacteria

2018 ◽  
Vol 6 (3) ◽  
pp. 73 ◽  
Author(s):  
Lucky Mulwa ◽  
Marc Stadler
Keyword(s):  
Broad Spectrum ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Public Health Issue ◽  
Target Cells ◽  
Global Public Health ◽  
Drug Candidates ◽  
Antiviral Compounds ◽  
Spectrum Activity

Viral infections including human immunodeficiency virus (HIV), cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) pose an ongoing threat to human health due to the lack of effective therapeutic agents. The re-emergence of old viral diseases such as the recent Ebola outbreaks in West Africa represents a global public health issue. Drug resistance and toxicity to target cells are the major challenges for the current antiviral agents. Therefore, there is a need for identifying agents with novel modes of action and improved efficacy. Viral-based illnesses are further aggravated by co-infections, such as an HIV patient co-infected with HBV or HCV. The drugs used to treat or manage HIV tend to increase the pathogenesis of HBV and HCV. Hence, novel antiviral drug candidates should ideally have broad-spectrum activity and no negative drug-drug interactions. Myxobacteria are in the focus of this review since they produce numerous structurally and functionally unique bioactive compounds, which have only recently been screened for antiviral effects. This research has already led to some interesting findings, including the discovery of several candidate compounds with broad-spectrum antiviral activity. The present review looks at myxobacteria-derived antiviral secondary metabolites.

scholarly journals Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses

2020 ◽  
Author(s):  
Xi Yu ◽  
Liming Zhang ◽  
Liangqin Tong ◽  
Nana Zhang ◽  
Han Wang ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Lipase Activity ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Viral Envelope ◽  
Global Public Health ◽  
Virucidal Activity ◽  
Extracellular Milieu

AbstractViruses are the major aetiological agents of acute and chronic severe human diseases that place a tremendous burden on global public health and economy; however, for most viruses, effective prophylactics and therapeutics are lacking, in particular, broad-spectrum antiviral agents. Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation of CbAE-1 in its lipase motif fully abrogated the virucidal ability. Furthermore, CbAE-2 presented low toxicity in vivo and in vitro, highlighting its potential as a broad-spectrum antiviral drug.

scholarly journals Antiviral Activity of Umifenovir In Vitro against a Broad Spectrum of Coronaviruses, Including the Novel SARS-CoV-2 Virus

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1665
Author(s):  
Irina Leneva ◽  
Nadezhda Kartashova ◽  
Artem Poromov ◽  
Anastasiia Gracheva ◽  
Ekaterina Korchevaya ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Viral Infections ◽  
Plaque Assay ◽  
Antiviral Drug ◽  
Antiviral Effect ◽  
In Vitro Assays ◽  
The Novel ◽  
Spectrum Activity ◽  
Broad Spectrum Activity

An escalating pandemic of the novel SARS-CoV-2 virus is impacting global health, and effective antivirals are needed. Umifenovir (Arbidol) is an indole-derivative molecule, licensed in Russia and China for prophylaxis and treatment of influenza and other respiratory viral infections. It has been shown that umifenovir has broad spectrum activity against different viruses. We evaluated the sensitivity of different coronaviruses, including the novel SARS-CoV-2 virus, to umifenovir using in vitro assays. Using a plaque assay, we revealed an antiviral effect of umifenovir against seasonal HCoV-229E and HCoV-OC43 coronaviruses in Vero E6 cells, with estimated 50% effective concentrations (EC50) of 10.0 ± 0.5 µM and 9.0 ± 0.4 µM, respectively. Umifenovir at 90 µM significantly suppressed plaque formation in CMK-AH-1 cells infected with SARS-CoV. Umifenovir also inhibited the replication of SARS-CoV-2 virus, with EC50 values ranging from 15.37 ± 3.6 to 28.0 ± 1.0 µM. In addition, 21–36 µM of umifenovir significantly suppressed SARS-CoV-2 virus titers (≥2 log TCID50/mL) in the first 24 h after infection. Repurposing of antiviral drugs is very helpful in fighting COVID-19. A safe, pan-antiviral drug such as umifenovir could be extremely beneficial in combating the early stages of a viral pandemic.

scholarly journals Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

2021 ◽  
Vol 9 (7) ◽  
pp. 1519
Author(s):  
Sonia R. Isaacs ◽  
Dylan B. Foskett ◽  
Anna J. Maxwell ◽  
Emily J. Ward ◽  
Clare L. Faulkner ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Viral Infections ◽  
Antiviral Drug ◽  
Virus Detection ◽  
Detection Methods ◽  
Islet Autoimmunity ◽  
Comprehensive Overview ◽  
Drug Candidates

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, as well as mechanistic studies of virus-infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here, we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

scholarly journals Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Keivan Zandi ◽  
Leda Bassit ◽  
Franck Amblard ◽  
Bryan D. Cox ◽  
Pouya Hassandarvish ◽  
...  
Keyword(s):  
Japanese Encephalitis ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Public Health Problem ◽  
Nucleoside Analogs ◽  
Global Public Health ◽  
Direct Acting Antiviral ◽  
East And Southeast Asia ◽  
Direct Acting ◽  
Global Public Health Problem

ABSTRACTDengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from theFlaviviridaefamily. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no U.S. FDA-approved antiviral drugs available to treat or to prevent DENV and JEV infections, leaving nearly one-third of the world’s population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs, as a class, are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activities across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2′-C-methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2, which recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and a structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections.

scholarly journals Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 176 ◽  
Author(s):  
Michela Mazzon ◽  
Ana Ortega-Prieto ◽  
Douglas Imrie ◽  
Christin Luft ◽  
Lena Hess ◽  
...  
Keyword(s):  
Viral Entry ◽  
Broad Spectrum ◽  
Well Being ◽  
Screening Strategy ◽  
Life Cycles ◽  
Antiviral Compounds ◽  
Spectrum Activity ◽  
Cellular Pathways ◽  
Broad Spectrum Activity ◽  
Economic Well Being

Viruses are a major threat to human health and economic well-being. In recent years Ebola, Zika, influenza, and chikungunya virus epidemics have raised awareness that infections can spread rapidly before vaccines or specific antagonists can be made available. Broad-spectrum antivirals are drugs with the potential to inhibit infection by viruses from different groups or families, which may be deployed during outbreaks when specific diagnostics, vaccines or directly acting antivirals are not available. While pathogen-directed approaches are generally effective against a few closely related viruses, targeting cellular pathways used by multiple viral agents can have broad-spectrum efficacy. Virus entry, particularly clathrin-mediated endocytosis, constitutes an attractive target as it is used by many viruses. Using a phenotypic screening strategy where the inhibitory activity of small molecules was sequentially tested against different viruses, we identified 12 compounds with broad-spectrum activity, and found a subset blocking viral internalisation and/or fusion. Importantly, we show that compounds identified with this approach can reduce viral replication in a mouse model of Zika infection. This work provides proof of concept that it is possible to identify broad-spectrum inhibitors by iterative phenotypic screenings, and that inhibition of host-pathways critical for viral life cycles can be an effective antiviral strategy.

scholarly journals Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

2021 ◽  
Author(s):  
Sonia R Isaacs ◽  
Dylan B Foskett ◽  
Anna J Maxwell ◽  
Emily J Ward ◽  
Clare L Faulkner ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Viral Infections ◽  
Antiviral Drug ◽  
Virus Detection ◽  
Detection Methods ◽  
Islet Autoimmunity ◽  
Comprehensive Overview ◽  
Drug Candidates

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, and mechanistic studies of virus infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses, and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

scholarly journals NAD+-consuming enzymes in immune defense against viral infection

2021 ◽  
Vol 478 (23) ◽  
pp. 4071-4092
Author(s):  
Jialin Shang ◽  
Michael R. Smith ◽  
Ananya Anmangandla ◽  
Hening Lin
Keyword(s):  
Immune Responses ◽  
Broad Spectrum ◽  
Defense Mechanisms ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Scientific Progress ◽  
Immune Defense ◽  
Past Century ◽  
Antiviral Immune Response ◽  
Antiviral Function

The COVID-19 pandemic reminds us that in spite of the scientific progress in the past century, there is a lack of general antiviral strategies. In analogy to broad-spectrum antibiotics as antibacterial agents, developing broad spectrum antiviral agents would buy us time for the development of vaccines and treatments for future viral infections. In addition to targeting viral factors, a possible strategy is to understand host immune defense mechanisms and develop methods to boost the antiviral immune response. Here we summarize the role of NAD+-consuming enzymes in the immune defense against viral infections, with the hope that a better understanding of this process could help to develop better antiviral therapeutics targeting these enzymes. These NAD+-consuming enzymes include PARPs, sirtuins, CD38, and SARM1. Among these, the antiviral function of PARPs is particularly important and will be a focus of this review. Interestingly, NAD+ biosynthetic enzymes are also implicated in immune responses. In addition, many viruses, including SARS-CoV-2 contain a macrodomain-containing protein (NSP3 in SARS-CoV-2), which serves to counteract the antiviral function of host PARPs. Therefore, NAD+ and NAD+-consuming enzymes play crucial roles in immune responses against viral infections and detailed mechanistic understandings in the future will likely facilitate the development of general antiviral strategies.

scholarly journals Discovery of Antivirals Using Phage Display

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1120
Author(s):  
Esen Sokullu ◽  
Marie-Soleil Gauthier ◽  
Benoit Coulombe
Keyword(s):  
Phage Display ◽  
Viral Infections ◽  
Human Mobility ◽  
Antiviral Agents ◽  
Drug Market ◽  
Screening Methods ◽  
Global Public Health ◽  
Drug Molecules ◽  
Phage Display Libraries ◽  
Short Period

The latest coronavirus disease outbreak, COVID-19, has brought attention to viral infections which have posed serious health threats to humankind throughout history. The rapid global spread of COVID-19 is attributed to the increased human mobility of today’s world, yet the threat of viral infections to global public health is expected to increase continuously in part due to increasing human–animal interface. Development of antiviral agents is crucial to combat both existing and novel viral infections. Recently, there is a growing interest in peptide/protein-based drug molecules. Antibodies are becoming especially predominant in the drug market. Indeed, in a remarkably short period, four antibody therapeutics were authorized for emergency use in COVID-19 treatment in the US, Russia, and India as of November 2020. Phage display has been one of the most widely used screening methods for peptide/antibody drug discovery. Several phage display-derived biologics are already in the market, and the expiration of intellectual property rights of phage-display antibody discovery platforms suggests an increment in antibody drugs in the near future. This review summarizes the most common phage display libraries used in antiviral discovery, highlights the approaches employed to enhance the antiviral potency of selected peptides/antibody fragments, and finally provides a discussion about the present status of the developed antivirals in clinic.

scholarly journals ANTIVIRAL PROPERTIES OF MICROALGAE AND CYANOBACTERIA

2021 ◽  
Vol 9 (Spl-1- GCSGD_2020) ◽  
pp. S43-S48
Author(s):  
Manishaa Sri Mahendran ◽  
◽  
Sinouvassane Djearamane ◽  
Ling Shing Wong ◽  
Govindaraju Kasivelu ◽  
...  
Keyword(s):  
Viral Infections ◽  
Virus Disease ◽  
Antiviral Agents ◽  
Freshwater Microalgae ◽  
Algal Biotechnology ◽  
Antiviral Compounds ◽  
Recent Outbreak ◽  
Respiratory Treatment ◽  
Algal Polysaccharides ◽  
Methods Of Treatment

The recent outbreak of Corona Virus Disease (COVID-19) and the surge in accelerating the development of a vaccine to fight against the SARS-CoV-2 virus has imposed greater challenges to humanity worldwide. There is lack of research into the production of effective vaccines and methods of treatment against viral infections. As of now, strategies encompassing antiviral drugs and corticosteroids alongside mechanical respiratory treatment are in practice as frontline treatments. Though studies have reported that microalgae possess antiviral properties, only a few cases have presented the existence of antiviral compounds such as algal polysaccharides, lectins, aggluttinins, scytovirin, algal lipids such as sulfoquinovosyldiacylglycerol (SQDG), monogalactosyldiacylglycerides (MGDG) and digalactosyldiacylglycerides (DGDG), and algal biopigments especially chlorophyll analogues, marennine, phycobiliproteins, phycocyanin, phycoerythrin and allophycocyanin that are derived from marine and freshwater microalgae. Given the chemodiversity of bioactive compounds from microalgae and the present scenario, algal biotechnology is seen as a prospective source of antiviral and anti-inflammatory compounds that can be used to develop antiviral agents. Microalgae with potential as antivirals and microalgae derived functional compounds to treat viral diseases are summarized and can be used as a reference in developing algae-derived antivirals to treat SARS-CoV-2 and other similar viruses.

scholarly journals Genome-scale CRISPR Screens Identify Host Factors that Promote Human Coronavirus Infection

2021 ◽  
Author(s):  
Marco Grodzki ◽  
Andrew P Bluhm ◽  
Moritz Schafer ◽  
Abderrahmane Tagmount ◽  
Max Russo ◽  
...  
Keyword(s):  
Antiviral Drug ◽  
Host Factors ◽  
Human Coronavirus ◽  
Antiviral Therapies ◽  
Antiviral Compounds ◽  
Number Of Factors ◽  
Host Cell Interactions ◽  
Spectrum Activity ◽  
Cycle Regulation ◽  
Genome Scale

The COVID-19 pandemic has resulted in 153 million infections and 3.2 million deaths as of May 2021. While effective vaccines are being administered globally, there is still a great need for antiviral therapies as potentially antigenically distinct SARS-CoV-2 variants continue to emerge across the globe. Viruses require host factors at every step in their life cycle, representing a rich pool of candidate targets for antiviral drug design. To identify host factors that promote SARS-CoV-2 infection with potential for broad-spectrum activity across the coronavirus family, we performed genome-scale CRISPR knockout screens in two cell lines (Vero E6 and HEK293T ectopically expressing ACE2) with SARS-CoV-2 and the common cold-causing human coronavirus OC43. While we identified multiple genes and functional pathways that have been previously reported to promote human coronavirus replication, we also identified a substantial number of novel genes and pathways. Of note, host factors involved in cell cycle regulation were enriched in our screens as were several key components of the programmed mRNA decay pathway. Finally, we identified novel candidate antiviral compounds targeting a number of factors revealed by our screens. Overall, our studies substantiate and expand the growing body of literature focused on understanding key human coronavirus-host cell interactions and exploit that knowledge for rational antiviral drug development.

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