Anti viral Finishing on Texti les - An Overview

Alphaviruses are a prominent class of reemergent pathogens due to their globally expanding ranges, potential for lethality, and possible use as bioweapons. The absence of effective treatments for alphaviruses highlights the need for innovative strategies to identify antiviral agents. Primary screens that use noninfectious self-replicating RNAs, termed replicons, have been used to identify potential antiviral compounds for alphaviruses. Only inhibitors of viral genome replication, however, will be identified using replicons, which excludes many other druggable steps in the viral life cycle. To address this limitation, we developed a western equine encephalitis virus pseudoinfectious particle system that reproduces several crucial viral life cycle steps in addition to genome replication. We used this system to screen a library containing ~26,000 extracts derived from marine microbes, and we identified multiple bacterial strains that produce compounds with potential antiviral activity. We subsequently used pseudoinfectious particle and replicon assays in parallel to counterscreen candidate extracts, and followed antiviral activity during biochemical fractionation and purification to differentiate between inhibitors of viral entry and genome replication. This novel process led to the isolation of a known alphavirus entry inhibitor, bafilomycin, thereby validating the approach for the screening and identification of potential antiviral compounds.

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Pathogenic Viruses Commonly Present in the Oral Cavity and Relevant Antiviral Compounds Derived from Natural Products

Medicines ◽

10.3390/medicines5040120 ◽

2018 ◽

Vol 5 (4) ◽

pp. 120 ◽

Cited By ~ 4

Author(s):

Daisuke Asai ◽

Hideki Nakashima

Keyword(s):

Natural Products ◽

Oral Cavity ◽

Rational Design ◽

Large Scale ◽

Antiviral Agents ◽

Marine Sponges ◽

Design Strategies ◽

Screening Programs ◽

Human Oral Cavity ◽

Antiviral Compounds

Many viruses, such as human herpesviruses, may be present in the human oral cavity, but most are usually asymptomatic. However, if individuals become immunocompromised by age, illness, or as a side effect of therapy, these dormant viruses can be activated and produce a variety of pathological changes in the oral mucosa. Unfortunately, available treatments for viral infectious diseases are limited, because (1) there are diseases for which no treatment is available; (2) drug-resistant strains of virus may appear; (3) incomplete eradication of virus may lead to recurrence. Rational design strategies are widely used to optimize the potency and selectivity of drug candidates, but discovery of leads for new antiviral agents, especially leads with novel structures, still relies mostly on large-scale screening programs, and many hits are found among natural products, such as extracts of marine sponges, sea algae, plants, and arthropods. Here, we review representative viruses found in the human oral cavity and their effects, together with relevant antiviral compounds derived from natural products. We also highlight some recent emerging pharmaceutical technologies with potential to deliver antivirals more effectively for disease prevention and therapy.

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Biological Evaluation of Molecules of the azaBINOL Class as Antiviral Agents: Specific Inhibition of HIV-1 RNase H Activity by 7-Isopropoxy-8-(naphth-1-yl)quinoline

10.1101/525105 ◽

2019 ◽

Author(s):

Ross D. Overacker ◽

Somdev Banerjee ◽

George F. Neuhaus ◽

Selena Milicevic Sephton ◽

Alexander Herrmann ◽

...

Keyword(s):

Viral Entry ◽

Antiviral Agents ◽

Biological Evaluation ◽

Rnase H ◽

Synthetic Compounds ◽

Infectivity Assay ◽

Antiviral Compounds ◽

Specific Manner ◽

Drug Leads ◽

Hiv 1

AbstractInspired by bioactive biaryl-containing natural products found in plants and the marine environment, a series of synthetic compounds belonging to the azaBINOL chiral ligand family was evaluated for antiviral activity against HIV-1. Testing of 39 unique azaBINOLs in a singleround infectivity assay resulted in the identification of three promising antiviral compounds, including 7-isopropoxy-8-(naphth-1-yl)quinoline (azaBINOLB#24), which exhibited low-micromolar activity. The active compounds and several close structural analogues were further tested against three different HIV-1 envelope pseudotyped viruses as well as in a full-virus replication system (EASY-HIT). Mode-of-action studies using a time-of-addition assay indicated that azaBINOLB#24acts after viral entry but before viral assembly and budding. HIV-1 reverse transcriptase (RT) assays that individually test for polymerase and RNase H activity were used to demonstrate thatB#24inhibits RNase H activity, most likely allosterically. Further binding analysis using bio-layer interferometry (BLI) showed thatB#24interacts with HIV-1 RT in a highly specific manner. These results indicate that azaBINOLB#24is a potentially viable, novel lead for the development of new HIV-1 RNase H inhibitors. Furthermore, this study demonstrates that the survey of libraries of synthetic compounds, designed purely with the goal of facilitating chemical synthesis in mind, may yield unexpected and selective drug leads for the development of new antiviral agents.

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Current Trends in SPR Biosensing of SARS-CoV-2 Entry Inhibitors

Chemosensors ◽

10.3390/chemosensors9120330 ◽

2021 ◽

Vol 9 (12) ◽

pp. 330

Author(s):

Elba Mauriz ◽

Laura M. Lechuga

Keyword(s):

High Throughput Screening ◽

Antiviral Agents ◽

Host Cells ◽

Binding Affinities ◽

Entry Inhibitors ◽

Antiviral Compounds ◽

Current Trends ◽

Main Protease ◽

Emerging Risk ◽

Repurposed Drugs

The emerging risk of viral diseases has triggered the search for preventive and therapeutic agents. Since the beginning of the COVID-19 pandemic, greater efforts have been devoted to investigating virus entry mechanisms into host cells. The feasibility of plasmonic sensing technologies for screening interactions of small molecules in real time, while providing the pharmacokinetic drug profiling of potential antiviral compounds, offers an advantageous approach over other biophysical methods. This review summarizes recent advancements in the drug discovery process of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) inhibitors using Surface Plasmon Resonance (SPR) biosensors. A variety of SPR assay formats are discussed according to the binding kinetics and drug efficacies of both natural products and repurposed drugs. Special attention has been given to the targeting of antiviral agents that block the receptor binding domain of the spike protein (RBD-S) and the main protease (3CLpro) of SARS-CoV-2. The functionality of plasmonic biosensors for high-throughput screening of entry virus inhibitors was also reviewed taking into account experimental parameters (binding affinities, selectivity, stability), potential limitations and future applications.

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Recent Advances in Tetrazole Derivatives as Potential Antiviral Agents

Asian Journal of Chemistry ◽

10.14233/ajchem.2021.23443 ◽

2021 ◽

Vol 33 (11) ◽

pp. 2599-2607

Author(s):

Ruchika Yogesh ◽

Noopur Srivastava

Keyword(s):

Antiviral Agents ◽

Acid Amide ◽

Host Cells ◽

Carboxylic Acid Amide ◽

Synthetic Compounds ◽

Scientific Databases ◽

The Past ◽

Antiviral Compounds ◽

Pharmaceutical Agents ◽

Tetrazole Derivatives

Viruses use the host cell’s biochemical machinery for replication and survival; and also undergo mutations to evade the immune response and achieve better transmission. These features make it challenging to develop selective drugs to kill viruses only and not the host cells. New and effective pharmaceutical agents are required to overcome this challenge. Tetrazole moiety, as a bio-isostere of carboxylic acid/amide group, has been extensively used as a potent pharmacophore in several bioactivities. Intrigued by the necessity of finding new antiviral compounds and tendency of tetrazole scaffolds to render various bioactivity profiles, this review article comprising literature reports of tetrazole-based synthetic compounds with promising antiviral activity is presented. This review comprises significant literature reports from the scientific databases published during the past four decades. It is found that tetrazole based molecules are promising endeavor for the development of potential agents against influenza virus, HIV, HCV and other viruses.

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Antibiotic-Mediated Inhibition of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection: A Novel Quinolone Function Which Potentiates the Antiviral Cytokine Response in MARC-145 Cells and Pig Macrophages

Virology Research and Treatment ◽

10.4137/vrt.s527 ◽

2008 ◽

Vol 1 ◽

pp. VRT.S527

Author(s):

William A. Cafruny ◽

Richard G. Duman ◽

Raymond R. Rowland ◽

Eric A. Nelson ◽

Grace H. Wong

Keyword(s):

Nalidixic Acid ◽

Antiviral Agents ◽

Respiratory Syndrome Virus ◽

Antiviral Compounds ◽

Primary Mouse ◽

Mouse Macrophages ◽

Microbial Infections ◽

Reduced Toxicity ◽

Actin Expression

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically significant agent for which there currently are no effective treatments. Development of antiviral agents for PRRSV as well as many other viruses has been limited by toxicity of known antiviral compounds. In contrast, antibiotics for non-virus microbial infections have been widely useful, in part because of their acceptable toxicity in animals. We report here the discovery that the quinolone-containing compound Plasmocin™, as well as the quinolones nalidixic acid and ciprofloxacin, have potent anti-PRRSV activity in vitro. PRRSV replication was inhibited by these antibiotics in both cultured MARC-145 cells and cultured primary alveolar porcine macrophages (PAMs). Furthermore, sub-optimal concentrations of nalidixic acid synergized with antiviral cytokines (AK-2 or IFN-γ) to quantitatively and qualitatively inhibit PRRSV replication in MARC-145 cells or PAMs. The antiviral activity of Plasmocin and nalidixic acid correlated with reduced actin expression in MARC-145 cells. Replication of the related lactate dehydrogenase-elevating virus (LDV) was also inhibited in primary mouse macrophages by Plasmocin. These results are significant to the development of antiviral strategies with potentially reduced toxicity, and provide a model system to better understand regulation of arterivirus replication.

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Discovery of Bioactive Natural Products for the Treatment of Acute Respiratory Infections – An Integrated Approach

Planta Medica ◽

10.1055/a-0590-5153 ◽

2018 ◽

Vol 84 (09/10) ◽

pp. 684-695 ◽

Cited By ~ 5

Author(s):

Ulrike Grienke ◽

Christina Mair ◽

Johannes Kirchmair ◽

Michaela Schmidtke ◽

Judith Rollinger

Keyword(s):

Antiviral Activity ◽

Respiratory Infections ◽

Antiviral Agents ◽

Integrated Approach ◽

Coxsackie Virus ◽

Acute Respiratory Infections ◽

Bioactive Natural Products ◽

Antiviral Compounds ◽

Antiviral Activities ◽

Selection Of

AbstractIn this work, an integrated approach for the identification of new antiviral agents from natural sources for the treatment of acute respiratory infections is presented. The approach comprises (i) the selection of starting material based on traditional knowledge, (ii) phenotypic screening of extracts for antiviral activity, and (iii) the implementation of in silico predictions to identify antiviral compounds and derive the molecular mechanism underlying their biological activity. A variety of starting materials from plants and fungi was selected for the production of 162 extracts. These extracts were tested in cytopathic effect inhibition assays against influenza virus A/Hong Kong/68 (HK/68), rhinovirus A2 (RV-A2), and coxsackie virus B3 (CV-B3). All extracts were also evaluated regarding their cytotoxicity. At an IC50 threshold of 50 µg/mL, 20, 11, and 14% of all tested extracts showed antiviral activity against HK/68, CV-B3, and RV-A2, respectively. Among all active extracts (n = 47), 68% showed antiviral activity against one of the investigated viruses, whereas 31% inhibited at least two viruses. Herein, we present a comprehensive dataset of probed extracts along with their antiviral activities and cytotoxicity. Application examples presented in this work illustrate the phytochemical workflow for the identification of antiviral natural compounds. We also discuss the challenges, pitfalls, and advantages of the integrated approach.

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Secondary Metabolites from Caulerpa Cylindracea (Sonder) Could Be Alternative Natural Antiviral Compounds for COVID-19: A Further in Silico Proof

10.26434/chemrxiv.13353473.v1 ◽

2020 ◽

Author(s):

Levent Çavaş ◽

Cengizhan Dag ◽

Miguel Carmena-Barreño ◽

Carlos Martínez-Cortés ◽

José Pedro Cerón-Carrasco ◽

...

Keyword(s):

Secondary Metabolites ◽

Vaccine Development ◽

Antiviral Agents ◽

Binding Energies ◽

Antiviral Compounds ◽

Main Protease ◽

The Us ◽

The World ◽

Molecular Dynamics Results ◽

Spreading Property

SARS-CoV-2 has been exhibiting extremely spreading property all around the world since its existence from Wuhan-China in December-2019. Although it has caused a death toll of over than 1.3 M people, no validated vaccine has been proposed yet. On the other hand, very dense studies on the vaccine development have been carrying out in some countries such as the US, Germany, UK, China and Russia. Due to side effects of current antiviral agents used in the therapy of COVID-19, there is a great need for the development of alternative compounds for this disease. Caulerpin (CPN) and caulerpenyne (CYN), predominant natural secondary metabolites from invasive marine green algae Caulerpa cylindracea,are proposed to neutralize the virus from two targets: spike protein (5XLR) and main protease (6YB7) in this study. The results show that the binding energies related to CPN-6YB7 and CYN-6YB7 interactions are found to be -8.02 kcal/mol and -6.83 kcal/mol, respectively. The binding energies were -9.68 kcal/mol and -7.53 kcal/mol, respectively, for CPN-5XLR and CYN-5XLR. In the molecular dynamics results, RMSD values show that CPN and CYN can form stable complexes with the proteins where CYN is more stable with 6YB7 and CPN interacts better with 5XLR. These differences seem to be based on the type of interactions of the complexes. In conclusion, caulerpin and caulerpenyne can further be investigated experimentally for their anti-SARS-CoV-2 efficiency.

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ANTIVIRAL PROPERTIES OF MICROALGAE AND CYANOBACTERIA

Journal of Experimental Biology and Agricultural Sciences ◽

10.18006/2021.9(spl-1-gcsgd_2020).s43.s48 ◽

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.

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Secondary Metabolites from Caulerpa Cylindracea (Sonder) Could Be Alternative Natural Antiviral Compounds for COVID-19: A Further in Silico Proof

10.26434/chemrxiv.13353473.v2 ◽

2020 ◽

Author(s):

Levent Çavaş ◽

Cengizhan Dag ◽

Miguel Carmena-Bargueño ◽

Carlos Martínez-Cortés ◽

José Pedro Cerón-Carrasco ◽

...

Keyword(s):

Secondary Metabolites ◽

Vaccine Development ◽

Antiviral Agents ◽

Binding Energies ◽

Antiviral Compounds ◽

Main Protease ◽

The Us ◽

The World ◽

Molecular Dynamics Results ◽

Spreading Property

SARS-CoV-2 has been exhibiting extremely spreading property all around the world since its existence from Wuhan-China in December-2019. Although it has caused a death toll of over than 1.3 M people, no validated vaccine has been proposed yet. On the other hand, very dense studies on the vaccine development have been carrying out in some countries such as the US, Germany, UK, China and Russia. Due to side effects of current antiviral agents used in the therapy of COVID-19, there is a great need for the development of alternative compounds for this disease. Caulerpin (CPN) and caulerpenyne (CYN), predominant natural secondary metabolites from invasive marine green algae Caulerpa cylindracea,are proposed to neutralize the virus from two targets: spike protein (5XLR) and main protease (6YB7) in this study. The results show that the binding energies related to CPN-6YB7 and CYN-6YB7 interactions are found to be -8.02 kcal/mol and -6.83 kcal/mol, respectively. The binding energies were -9.68 kcal/mol and -7.53 kcal/mol, respectively, for CPN-5XLR and CYN-5XLR. In the molecular dynamics results, RMSD values show that CPN and CYN can form stable complexes with the proteins where CYN is more stable with 6YB7 and CPN interacts better with 5XLR. These differences seem to be based on the type of interactions of the complexes. In conclusion, caulerpin and caulerpenyne can further be investigated experimentally for their anti-SARS-CoV-2 efficiency.

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