scholarly journals Antiviral activities and applications of ribosomally synthesized and post-translationally modified peptides (RiPPs)

2021 ◽  
Author(s):  
Yuxin Fu ◽  
Ate H. Jaarsma ◽  
Oscar P. Kuipers
Keyword(s):  
Antiviral Therapy ◽  
Antiviral Drug ◽  
Viral Disease ◽  
Antimicrobial Activities ◽  
Antiviral Drugs ◽  
Global Public Health ◽  
Enveloped Viruses ◽  
Small Molecule Drugs ◽  
Modified Peptides ◽  
Antiviral Activities

AbstractThe emergence and re-emergence of viral epidemics and the risks of antiviral drug resistance are a serious threat to global public health. New options to supplement or replace currently used drugs for antiviral therapy are urgently needed. The research in the field of ribosomally synthesized and post-translationally modified peptides (RiPPs) has been booming in the last few decades, in particular in view of their strong antimicrobial activities and high stability. The RiPPs with antiviral activity, especially those against enveloped viruses, are now also gaining more interest. RiPPs have a number of advantages over small molecule drugs in terms of specificity and affinity for targets, and over protein-based drugs in terms of cellular penetrability, stability and size. Moreover, the great engineering potential of RiPPs provides an efficient way to optimize them as potent antiviral drugs candidates. These intrinsic advantages underscore the good therapeutic prospects of RiPPs in viral treatment. With the aim to highlight the underrated antiviral potential of RiPPs and explore their development as antiviral drugs, we review the current literature describing the antiviral activities and mechanisms of action of RiPPs, discussing the ongoing efforts to improve their antiviral potential and demonstrate their suitability as antiviral therapeutics. We propose that antiviral RiPPs may overcome the limits of peptide-based antiviral therapy, providing an innovative option for the treatment of viral disease.

scholarly journals Study of effectiveness of antiviral drugs (umifenovir, triazavirin) against acute respiratory viral infections

2018 ◽  
Vol 99 (2) ◽  
pp. 215-223 ◽  
Author(s):  
E P Tikhonova ◽  
T Yu Kuz'mina ◽  
N V Andronova ◽  
O A Tyushevskaya ◽  
T A Elistratova ◽  
...  
Keyword(s):  
Antiviral Therapy ◽  
Clinical Efficacy ◽  
Viral Infections ◽  
Clinical Symptoms ◽  
Antiviral Drug ◽  
Antiviral Drugs ◽  
Control Group ◽  
Efficacy And Safety ◽  
Respiratory Viral Infections ◽  
Adaptive Reactions

Aim. Comparative study of clinical efficacy and safety of antiviral drug triazavirin and umifenovir in the treatment of patients with acute respiratory viral infections and influenza. Methods. The study included 100 patients aged 18 to 65 years diagnosed with moderate acute respiratory viral infection. Group 1 included 34 patients receiving umifenovir 200 mg 4 times a day for 5 days, and comparison group included 32 patients who received triazavirin 1 capsule (250 mg) 3 times a day for 5 days. Group 3 (control group) included 34 patients not treated with antiviral therapy. Efficacy and safety of the studied antiviral drugs were evaluated based on clinical symptoms in the disease course and were confirmed by adaptive reactions of the organism. Results. Among patients receiving triazavirin, recovery time and fever, headache and catarrhal syndrome resolution time were less than among patients who received umifenovir. On triazavirin treatment with favorable tolerability, symptomatic medications (antipyretics) were discontinued, and the duration of their use was less, than in patients receiving umifenovir. Evaluation of clinical efficacy of umifenovir and triazavirin for the treatment of acute respiratory viral infections and influenza demonstrated that the drugs effectively reverse the main symptoms of the disease (p <0.05), reduce complications incidence (18.1±2.1% vs. 55.9±3.2%, p <0.05) and contribute to the stabilization of adaptive reactions of the organism in contrast to the results of patients not receiving etiotropic therapy (6.9±2.9% vs. 12.8±2.7, p <0.05). During the use of umifenovir by day 4 and during the use of triazavirin by day 3 intoxication and catarrhal syndromes had been reversed, while in case of the absence of antiviral therapy, 55.8% of patients had continuing intoxication and catarrhal symptoms. Conclusion. The results of the study allow defining umifenovir and triazavirin as the first line of defense against acute respiratory viral infections with good efficacy and tolerability of the drugs.

scholarly journals ENNAVIA is an innovative new method which employs neural networks for antiviral and anti-coronavirus activity prediction for therapeutic peptides

2021 ◽  
Author(s):  
Patrick Brendan Timmons ◽  
Chandralal M. Hewage
Keyword(s):  
In Silico ◽  
Antiviral Drug ◽  
Area Under The Curve ◽  
Antiviral Drugs ◽  
Test Accuracy ◽  
Sequencing Data ◽  
Drug Candidates ◽  
Therapeutic Peptides ◽  
Antiviral Activities ◽  
External Test

AbstractViruses represent one of the greatest threats to human health, necessitating the development of new antiviral drug candidates. Antiviral peptides often possess excellent biological activity and a favourable toxicity profile, and therefore represent a promising field of novel antiviral drugs. As the quantity of sequencing data grows annually, the development of an accurate in silico method for the prediction of peptide antiviral activities is important. This study leverages advances in deep learning and cheminformatics to produce a novel sequence-based deep neural network classifier for the prediction of antiviral peptide activity. The method out-performs the existent best-in-class, with an external test accuracy of 93.9%, Matthews correlation coefficient of 0.87 and an Area Under the Curve of 0.93 on the dataset of experimentally validated peptide activities. This cutting-edge classifier is available as an online web server at https://research.timmons.eu/ennavia, facilitating in silico screening and design of peptide antiviral drugs by the wider research community.

scholarly journals Broad-Spectrum Antiviral Entry Inhibition by Interfacially Active Peptides

2020 ◽  
Vol 94 (23) ◽  
Author(s):  
Andrew R. Hoffmann ◽  
Shantanu Guha ◽  
Eric Wu ◽  
Jenisha Ghimire ◽  
Yilin Wang ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
Mammalian Cells ◽  
Viral Disease ◽  
Antiviral Drugs ◽  
Viral Envelope ◽  
Molecular Characteristics ◽  
Enveloped Viruses ◽  
Interfacial Activity ◽  
Active Peptides

ABSTRACT Numerous peptides inhibit the entry of enveloped viruses into cells. Some of these peptides have been shown to inhibit multiple unrelated viruses. We have suggested that such broad-spectrum antiviral peptides share a property called interfacial activity; they are somewhat hydrophobic and amphipathic, with a propensity to interact with the interfacial zones of lipid bilayer membranes. In this study, we further tested the hypothesis that such interfacial activity is a correlate of broad-spectrum antiviral activity. In this study, several families of peptides, selected for the ability to partition into and disrupt membrane integrity but with no known antiviral activity, were tested for the ability to inhibit multiple diverse enveloped viruses. These include Lassa pseudovirus, influenza virus, dengue virus type 2, herpes simplex virus 1, and nonenveloped human adenovirus 5. Various families of interfacially active peptides caused potent inhibition of all enveloped viruses tested at low and submicromolar concentrations, well below the range in which they are toxic to mammalian cells. These membrane-active peptides block uptake and fusion with the host cell by rapidly and directly interacting with virions, destabilizing the viral envelope, and driving virus aggregation and/or intervirion envelope fusion. We speculate that the molecular characteristics shared by these peptides can be exploited to enable the design, optimization, or molecular evolution of novel broad-spectrum antiviral therapeutics. IMPORTANCE New classes of antiviral drugs are needed to treat the ever-changing viral disease landscape. Current antiviral drugs treat only a small number of viral diseases, leaving many patients with established or emerging infections to be treated solely with supportive care. Recent antiviral peptide research has produced numerous membrane-interacting peptides that inhibit diverse enveloped viruses in vitro and in vivo. Peptide therapeutics are becoming more common, with over 60 FDA-approved peptides for clinical use. Included in this class of therapeutics is enfuvirtide, a 36-residue peptide drug that inhibits HIV entry/fusion. Due to their broad-spectrum mechanism of action and enormous potential sequence diversity, peptides that inhibit virus entry could potentially fulfill the need for new antiviral therapeutics; however, a better understanding of their mechanism is needed for the optimization or evolution of sequence design to combat the wide landscape of viral disease.

scholarly journals Multifaceted Functions of CH25H and 25HC to Modulate the Lipid Metabolism, Immune Responses, and Broadly Antiviral Activities

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 727 ◽  
Author(s):  
Jin Zhao ◽  
Jiaoshan Chen ◽  
Minchao Li ◽  
Musha Chen ◽  
Caijun Sun
Keyword(s):  
Lipid Metabolism ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Cholesterol Metabolism ◽  
Rift Valley Fever Virus ◽  
Antiviral Drug ◽  
Emerging Infectious Diseases ◽  
Cholesterol Homeostasis ◽  
Global Public Health ◽  
Antiviral Activities

With the frequent outbreaks of emerging infectious diseases in recent years, an effective broad-spectrum antiviral drug is becoming an urgent need for global public health. Cholesterol-25-hydroxylase (CH25H) and its enzymatic products 25-hydroxycholesterol (25HC), a well-known oxysterol that regulates lipid metabolism, have been reported to play multiple functions in modulating cholesterol homeostasis, inflammation, and immune responses. CH25H and 25HC were recently identified as exerting broadly antiviral activities, including upon a variety of highly pathogenic viruses such as human immunodeficiency virus (HIV), Ebola virus (EBOV), Nipah virus (NiV), Rift Valley fever virus (RVFV), and Zika virus (ZIKV). The underlying mechanisms for its antiviral activities are being extensively investigated but have not yet been fully clarified. In this study, we summarized the current findings on how CH25H and 25HC play multiple roles to modulate cholesterol metabolism, inflammation, immunity, and antiviral infections. Overall, 25HC should be further studied as a potential therapeutic agent to control emerging infectious diseases in the future.

scholarly journals Construction of a non-infectious SARS-CoV-2 replicon for antiviral drug testing and gene function studies

2021 ◽  
Author(s):  
Hai Trong Nguyen ◽  
Darryl Falzarano ◽  
Volker Gerdts ◽  
Qiang Liu
Keyword(s):  
Drug Testing ◽  
Reverse Genetics ◽  
Antiviral Drug ◽  
Antiviral Drugs ◽  
Dependent Manner ◽  
Global Public Health ◽  
Structural Protein ◽  
Reporter System ◽  
Viral Pathogen ◽  
Public Health Emergencies

The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread worldwide resulting in global public health emergencies and economic crises. In this study, a non-infectious and biocontainment level-2 compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily quantifiable, and high-throughput adaptable. Upon transfecting the SARS-CoV-2 replicon BAC plasmid DNA into Vero E6 cells, we could detect high levels of nLuc reporter activity and viral RNA transcript, suggesting the replication of the replicon. The replicon replication was further demonstrated by the findings that deleting non-structural protein 15 or mutating its catalytic sites significantly reduced replicon replication, whereas providing the nucleocapsid protein in trans enhanced replicon replication in a dose-dependent manner. Finally, we showed that remdesivir, an FDA-approved antiviral drug, significantly inhibited the replication of the replicon, providing proof-of-principle for the application of our replicon as a useful tool for developing antivirals. Taken together, this study established a sensitive and BSL-2 compatible reporter system in a single BAC plasmid for investigating the functions of SARS-CoV-2 proteins in viral replication and evaluating antiviral compounds. This should contribute to the global effort to combat this deadly viral pathogen. IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 is having a catastrophic impact on human lives. Combatting the pandemic requires effective vaccines and antiviral drugs. In this study, we developed a SARS-CoV-2 replicon system with a sensitive and easily quantifiable reporter. Unlike studies involving infectious SARS-CoV-2 virus that must be performed in a biosafety level (BSL) 3 facility, the replicon is non-infectious and thus can be safely used in BSL2 laboratories. The replicon will provide a valuable tool for testing antiviral drugs and studying SARS-CoV-2 biology.

scholarly journals Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 367
Author(s):  
Mohd Ishtiaq Anasir ◽  
Babu Ramanathan ◽  
Chit Laa Poh
Keyword(s):  
Drug Discovery ◽  
Dengue Virus ◽  
Structural Information ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Denv Infection ◽  
Antiviral Drugs ◽  
Global Public Health ◽  
Viral Attachment ◽  
E Protein

Dengue virus (DENV) presents a significant threat to global public health with more than 500,000 hospitalizations and 25,000 deaths annually. Currently, there is no clinically approved antiviral drug to treat DENV infection. The envelope (E) glycoprotein of DENV is a promising target for drug discovery as the E protein is important for viral attachment and fusion. Understanding the structure and function of DENV E protein has led to the exploration of structure-based drug discovery of antiviral compounds and peptides against DENV infections. This review summarizes the structural information of the DENV E protein with regards to DENV attachment and fusion. The information enables the development of antiviral agents through structure-based approaches. In addition, this review compares the potency of antivirals targeting the E protein with the antivirals targeting DENV multifunctional enzymes, repurposed drugs and clinically approved antiviral drugs. None of the current DENV antiviral candidates possess potency similar to the approved antiviral drugs which indicates that more efforts and resources must be invested before an effective DENV drug materializes.

scholarly journals Antioxidant Potential of Antiviral Drug Umifenovir

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1577 ◽  
Author(s):  
Elena V. Proskurnina ◽  
Dmitry Yu. Izmailov ◽  
Madina M. Sozarukova ◽  
Tatiana A. Zhuravleva ◽  
Irina A. Leneva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Antioxidant Capacity ◽  
Antiviral Drug ◽  
Radical Scavenging ◽  
Viral Disease ◽  
Reaction Scheme ◽  
Antiviral Drugs ◽  
Antioxidant Effect ◽  
Total Antioxidant

Free radical reactions play an important role in biological functions of living systems. The balance between oxidants and antioxidants is necessary for the normal homeostasis of cells and organisms. Experimental works demonstrate the role of oxidative stress that is caused by influenza virus as well as the toxic effects of some antiviral drugs. Therefore, antiviral drugs should be characterized by its pro- and antioxidant activity, because it can affect its therapeutic efficiency. The aim of the study was to quantify the antioxidant capacity and propose the mechanism of the antioxidant effect of the antiviral drug Umifenovir (Arbidol®). The kinetic chemiluminescence with the 2,2’-azobis (2-amidinopropane) dihydrochloride + luminol system was used to quantify the antioxidant capacity of Umifenovir relative to the standard compound Trolox. With computer simulation, the reaction scheme and rate constants were proposed. The antioxidant capacity of 0.9 μM Umifenovir (maximum concentration of Umifenovir in blood after oral administration of 200 mg) was as high as 1.65 ± 0.18 μM of Trolox. Thus, the total antioxidant capacity of Umifenovir is comparable to the antioxidant capacity of Trolox. Unlike Trolox, Umifenovir reacts with free radicals in two stages. For Trolox, the free radical scavenging rate constant was k = 2000 nM−1 min.−1, for Umifenovir k1 = 300 nM−1min.−1, k2 = 4 nM−1min.−1. Slower kinetics of Umifenovir provides the prolonged antioxidant effect when compared to Trolox. This phenomenon can make a serious contribution to the compensation of oxidative stress that is caused by a viral disease and the therapeutic effect of the drug.

scholarly journals A Review of Medicinal Plants with Antiviral Activity Available in Bangladesh and Mechanistic Insight Into Their Bioactive Metabolites on SARS-CoV-2, HIV and HBV

2021 ◽  
Vol 12 ◽  
Author(s):  
Sitesh C. Bachar ◽  
Kishor Mazumder ◽  
Ritesh Bachar ◽  
Asma Aktar ◽  
Mamun Al Mahtab
Keyword(s):  
Medicinal Plants ◽  
Antiviral Activity ◽  
Oleanolic Acid ◽  
Bioactive Compounds ◽  
In Silico ◽  
Hepatitis Virus ◽  
Antiviral Drug ◽  
Antiviral Drugs ◽  
Bioactive Metabolites ◽  
Antiviral Activities

Currently, viral infection is the most serious health issue which causing unexpected higher rate of death globally. Many viruses are not yet curable, such as corona virus-2 (SARS-CoV-2), human immunodeficiency virus (HIV), hepatitis virus, human papilloma virus and so others. Furthermore, the toxicities and ineffective responses to resistant strains of synthetic antiviral drugs have reinforced the search of effective and alternative treatment options, such as plant-derived antiviral drug molecules. Therefore, in the present review, an attempt has been taken to summarize the medicinal plants reported for exhibiting antiviral activities available in Bangladesh along with discussing the mechanistic insights into their bioactive components against three most hazardous viruses, namely SARS-CoV-2, HIV, and HBV. The review covers 46 medicinal plants with antiviral activity from 25 families. Among the reported 79 bioactive compounds having antiviral activities isolated from these plants, about 37 of them have been reported for significant activities against varieties of viruses. Hesperidin, apigenin, luteolin, seselin, 6-gingerol, humulene epoxide, quercetin, kaempferol, curcumin, and epigallocatechin-3-gallate (EGCG) have been reported to inhibit multiple molecular targets of SARS-CoV-2 viral replication in a number of in silico investigations. Besides, numerous in silico, in vitro, and in vivo bioassays have been demonstrated that EGCG, anolignan-A, and B, ajoene, curcumin, and oleanolic acid exhibit anti-HIV activity while piperine, ursolic acid, oleanolic acid, (+)-cycloolivil-4′-O-β-d-glucopyranoside, quercetin, EGCG, kaempferol, aloin, apigenin, rosmarinic acid, andrographolide, and hesperidin possess anti-HBV activity. Thus, the antiviral medicinal plants and the isolated bioactive compounds may be considered for further advanced investigations with the aim of the development of effective and affordable antiviral drugs.

Discovery of Some Antiviral Natural products to fight against Novel Corona Virus (SARS-CoV-2) using Insilico approach

2020 ◽  
Vol 23 ◽  
Author(s):  
Ashish Shah ◽  
Vaishali Patel ◽  
Bhumika Parmar
Keyword(s):  
Binding Affinity ◽  
Protein S ◽  
Docking Studies ◽  
Spike Protein ◽  
Enveloped Viruses ◽  
Bioactivity Prediction ◽  
Corona Virus ◽  
Main Protease ◽  
Antiviral Activities ◽  
Deadly Disease

Background: Novel Corona virus is a type of enveloped viruses with a single stranded RNA enclosing helical nucleocapsid. The envelope consists of spikes on the surface which are made up of proteins through which virus enters into human cells. Until now there is no specific drug or vaccine available to treat COVID-19 infection. In this scenario, reposting of drug or active molecules may provide rapid solution to fight against this deadly disease. Objective: We had selected 30 phytoconstituents from the different plants which are reported for antiviral activities against corona virus (CoVs) and performed insilico screening to find out phytoconstituents which have potency to inhibit specific target of novel corona virus. Methods: We had perform molecular docking studies on three different proteins of novel corona virus namely COVID-19 main protease (3CL pro), papain-like protease (PL pro) and spike protein (S) attached to ACE2 binding domain. The screening of the phytoconstituents on the basis of binding affinity compared to standard drugs. The validations of screened compounds were done using ADMET and bioactivity prediction. Results: We had screened five compounds biscoclaurine, norreticuline, amentoflavone, licoricidin and myricetin using insilico approach. All compounds found safe in insilico toxicity studies. Bioactivity prediction reviles that these all compounds may act through protease or enzyme inhibition. Results of compound biscoclaurine norreticuline were more interesting as this biscoclaurine had higher binding affinity for the target 3CLpro and PLpro targets and norreticuline had higher binding affinity for the target PLpro and Spike protein. Conclusion: Our study concludes that these compounds could be further explored rapidly as it may have potential to fight against COVID-19.

Punica granatum as a Source of Natural Antioxidant and Antimicrobial Agent; a Comprehensive Review on Related Investigations

2020 ◽  
Vol 17 ◽  
Author(s):  
Atefeh Jalali ◽  
Mohammadreza Kiafar ◽  
Masih Seddigh ◽  
Mohammad M. Zarshenas
Keyword(s):  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Natural Antioxidants ◽  
Punica Granatum ◽  
Antimicrobial Activities ◽  
Natural Antioxidant ◽  
Antiviral Activities ◽  
Natural Foods

Background: The consumption of natural antioxidants is increasing due to the demand and tendency to natural foods. Punica granatum L. [Punicaceae] is a fruit with various bioactive ingredients. The effectiveness of this plant has been proved against various disorders such as hyperglycemia, hyperlipidemia, blood coagulation, infections, cancer, and dentistry. Among them, there are numerous researches on antimicrobial and antioxidant properties. Subsequently, the present study aimed to compile a review of those properties to outline this herb as a possible natural antioxidant and preservative. Methods: Synchronically, keywords "Punica granatum" with antimicrobial, or antibacterial, antifungal, antiviral, antioxidant and radical scavenging were searched through "Scopus" database up to 31st September 2019. Papers focusing on agriculture, genetics, chemistry, and environmental sciences were excluded and also related papers were collected. Results: Among 201 papers focusing on related activities, 111 papers have dealt with antioxidant activities focusing based on DPPH assay, 59 with antibacterial, on both gram+ and gram- bacteria, 24 with antifungal effects, mostly on Aspergillus niger and Candida albicans, and 7 papers with antiviral activities. There were about 50 papers focusing on in-vivo antioxidant activities of this plant. Conclusion: Taken together, botanical parts of P. granatum have possessed notable radical scavenging and antimicrobial activities that with these properties, this plant can be introduced as a natural safe source of preservative and antioxidant. Accordingly, P. granatum can be applied as excipient with the aforementioned properties in the pharmaceutical and food industries.

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