scholarly journals Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 184 ◽  
Author(s):  
Salima Lalani ◽  
Chit Laa Poh

Flavonoids are natural biomolecules that are known to be effective antivirals. These biomolecules can act at different stages of viral infection, particularly at the molecular level to inhibit viral growth. Enterovirus A71 (EV-A71), a non-enveloped RNA virus, is one of the causative agents of hand, foot and mouth disease (HFMD), which is prevalent in Asia. Despite much effort, no clinically approved antiviral treatment is available for children suffering from HFMD. Flavonoids from plants serve as a vast reservoir of therapeutically active constituents that have been explored as potential antiviral candidates against RNA and DNA viruses. Here, we reviewed flavonoids as evidence-based natural sources of antivirals against non-picornaviruses and picornaviruses. The detailed molecular mechanisms involved in the inhibition of EV-A71 infections are discussed.

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 625
Author(s):  
Chonnamet Techasaensiri ◽  
Artit Wongsa ◽  
Thanyawee Puthanakit ◽  
Kulkanya Chokephaibulkit ◽  
Tawee Chotpitayasunondh ◽  
...  

Hand, foot, and mouth disease (HFMD) is highly prevalent in East and Southeast Asia. It particularly affects children under five years of age. The most common causative agents are coxsackieviruses A6 and A16, and enterovirus A71 (EV71). The clinical presentation is usually mild and self-limited, but, in some cases, severe and fatal complications develop. To date, no specific therapy or worldwide vaccine is available. In general, viral infection invokes both antibody and cell-mediated immune responses. Passive immunity transfer can ameliorate the severe symptoms of diseases such as COVID-19, influenza, MERS, and SARS. Hyperimmune plasma (HIP) from healthy donors with high anti-EV71 neutralizing titer were used to transfuse confirmed EV71-infected children with neurological involvement (n = 6). It resulted in recovery within three days, with no neurological sequelae apparent upon examination 14 days later. Following HIP treatment, plasma chemokines were decreased, whereas anti-inflammatory and pro-inflammatory cytokines gradually increased. Interestingly, IL-6 and G-CSF levels in cerebrospinal fluid declined sharply within three days. These findings indicate that HIP has therapeutic potential for HFMD with neurological complications. However, given the small number of patients who have been treated, a larger cohort study should be undertaken. Successful outcomes would stimulate the development of anti-EV71 monoclonal antibody therapy.


2020 ◽  
Author(s):  
Tao Zuo ◽  
Qin Liu ◽  
Fen Zhang ◽  
Yun Kit Yeoh ◽  
Yating Wan ◽  
...  

Abstract Background: Coronavirus Disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from faecal samples and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as the virome) that play a role in regulating host immunity and disease pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need.Methods: We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All subjects had faecal specimens sampled at inclusion. Blood specimens were collected for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serial faecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the faecal RNA and DNA virome. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters.Results: Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in faecal samples, compared to non-COVID-19 subjects. Such gut virome alterations persisted up to 30 days after disease resolution. Faecal virome in SARS-CoV-2 infection harboured more stress-, inflammation- and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Baseline fecal abundance of 10 virus species (1 RNA virus, Pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease COVID-19 severity. These viruses inversely correlated with blood levels of pro-inflammatory proteins, white cells and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects.Conclusions: Both enteric RNA and DNA virome in COVID-19 patients were different from non-COVID-19 subjects, which persisted after disease resolution of COVID-19. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age may partly explain that older subjects are prone to severe and worse COVID-19 outcomes. Altogether our data highlight the importance of human gut virome in severity and potentially therapeutics of COVID-19.


2020 ◽  
Author(s):  
Tao Zuo ◽  
Qin Liu ◽  
Fen Zhang ◽  
Yun Kit Yeoh ◽  
Yating Wan ◽  
...  

Abstract Background: Coronavirus Disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from faecal samples and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as virome) that play a role in regulating host immunity and pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need.Methods:We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All study subjects had faecal specimens sampled at inclusion. Blood specimens were sampled for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serially faecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the faecal RNA and DNA virome respectively. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters.Results: Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in faecal samples, compared to non-COVID-19 subjects. Such gut virome dysbiosis persisted up to 30 days after disease resolution. Faecal virome in SARS-CoV-2 infection harboured more stress-, inflammation- and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Human faecal baseline abundance of 10 virus species (1 RNA virus, Pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease severity of COVID-19. These viruses were also inversely associated with blood levels of pro-inflammatory proteins, white cells and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects.Conclusions: Both enteric RNA and DNA viromes were perturbed in COVID-19, which prolonged even after disease resolution. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age partly explains that older subjects are prone to severe and unfavorable COVID-19 outcomes. Our data altogether highlight the significance of human gut virome in COVID-19 disease course and potentially therapeutics.


Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Tao Zuo ◽  
Qin Liu ◽  
Fen Zhang ◽  
Yun Kit Yeoh ◽  
Yating Wan ◽  
...  

Abstract Background Coronavirus disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from fecal samples, and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as the virome) that play a role in regulating host immunity and disease pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need. Methods We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All subjects had fecal specimens sampled at inclusion. Blood specimens were collected for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serial fecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the fecal RNA and DNA virome. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters. Results Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in fecal samples, compared to non-COVID-19 subjects. Such gut virome alterations persisted up to 30 days after disease resolution. Fecal virome in SARS-CoV-2 infection harbored more stress-, inflammation-, and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Baseline fecal abundance of 10 virus species (1 RNA virus, pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease COVID-19 severity. These viruses inversely correlated with blood levels of pro-inflammatory proteins, white cells, and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects. Conclusions Both enteric RNA and DNA virome in COVID-19 patients were different from non-COVID-19 subjects, which persisted after disease resolution of COVID-19. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age may partly explain that older subjects are prone to severe and worse COVID-19 outcomes. Altogether, our data highlight the importance of human gut virome in severity and potentially therapeutics of COVID-19.


Background: Determination of molecular mechanisms of action of drugs forms a scientific basis for the directed search of efficient medications. Assumed pathways of interactions of chemotherapeutic drugs which affect infectious agents and malignant neoplasm with their potential molecular targets require direct evidences at the molecular level. Such evidences can be obtained by means of molecular biophysics which possesses an arsenal of new powerful physical techniques for studying the intermolecular interactions of biomolecules and pharmaceutical agents. Objectives: The aim of this review is the generalization of the results of long standing investigations on the molecular mechanisms of action of chemotherapeutic agents performed in the biophysical departments of B. Verkin Institute for Low Temperature Physics and Engineering (ILTPE) of the NAS of Ukraine. The first part of the review is devoted to anticancer and antiviral agents targeted presumably at nucleic acids. Materials and methods: Mass spectrometric studies of molecules of thermally unstable drugs and their complexes with biomolecules have been advanced significantly due to the development of soft ionization/desorption techniques; the researchers of ILTPE have made noticeable contribution to this field. The methods of molecular spectroscopy and computer modeling by means of quantum chemistry were applied in the combined investigations. Results: The objects of study were the systems composed of chemotherapeutic drugs – thiophosphamide, phenazine derivatives and phenazine-modified antigene/antisense oligonucleotides, quaternary compounds, tilorone – and their molecular targets – DNA, oligo- and polynucleotides and nucleic acids components. The mechanisms of action of these drugs established at the model molecular level consisted in the specific and nonspecific noncovalent or covalent interactions of the drugs’ molecules with nucleic acids and their components and in the formation of stable drug-target complexes. Conclusions: The experience of investigations conducted during several decades at the ILTPE has demonstrated the efficiency of the application of the methods and approaches of molecular biophysics to establishing of molecular mechanisms of drugs action. The basic results obtained are of practical importance for the further development of new efficient pharmaceuticals.


Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 732 ◽  
Author(s):  
Rashid Aman ◽  
Ahmed Mahas ◽  
Haroon Butt ◽  
Fatimah Aljedaani ◽  
Magdy Mahfouz

Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are key immune mechanisms helping prokaryotic species fend off RNA and DNA viruses. CRISPR/Cas9 has broad applications in basic research and biotechnology and has been widely used across eukaryotic species for genome engineering and functional analysis of genes. The recently developed CRISPR/Cas13 systems target RNA rather than DNA and thus offer new potential for transcriptome engineering and combatting RNA viruses. Here, we used CRISPR/LshCas13a to stably engineer Arabidopsis thaliana for interference against the RNA genome of Turnip mosaic virus (TuMV). Our data demonstrate that CRISPR RNAs (crRNAs) guiding Cas13a to the sequences encoding helper component proteinase silencing suppressor (HC-Pro) or GFP target 2 (GFP-T2) provide better interference compared to crRNAs targeting other regions of the TuMV RNA genome. This work demonstrates the exciting potential of CRISPR/Cas13 to be used as an antiviral strategy to obstruct RNA viruses, and encourages the search for more robust and effective Cas13 variants or CRISPR systems that can target RNA.


2018 ◽  
Vol 26 ◽  
pp. 204020661876129 ◽  
Author(s):  
Luděk Eyer ◽  
Radim Nencka ◽  
Erik de Clercq ◽  
Katherine Seley-Radtke ◽  
Daniel Růžek

Nucleoside analogs represent the largest class of small molecule-based antivirals, which currently form the backbone of chemotherapy of chronic infections caused by HIV, hepatitis B or C viruses, and herpes viruses. High antiviral potency and favorable pharmacokinetics parameters make some nucleoside analogs suitable also for the treatment of acute infections caused by other medically important RNA and DNA viruses. This review summarizes available information on antiviral research of nucleoside analogs against arthropod-borne members of the genus Flavivirus within the family Flaviviridae, being primarily focused on description of nucleoside inhibitors of flaviviral RNA-dependent RNA polymerase, methyltransferase, and helicase/NTPase. Inhibitors of intracellular nucleoside synthesis and newly discovered nucleoside derivatives with high antiflavivirus potency, whose modes of action are currently not completely understood, have drawn attention. Moreover, this review highlights important challenges and complications in nucleoside analog development and suggests possible strategies to overcome these limitations.


2020 ◽  
Vol 5 (1) ◽  
pp. 133 ◽  
Author(s):  
Jennifer Cadnum ◽  
Daniel F. Li ◽  
Lucas D. Jones ◽  
Sarah N. Redmond ◽  
Basya Pearlmutter ◽  
...  

Background:  Contaminated surfaces are a potential source for spread of respiratory viruses including SARS-CoV-2.  Ultraviolet-C (UV-C) light is effective against RNA and DNA viruses and could be useful for decontamination of high-touch fomites that are shared by multiple users. Methods:  A modification of the American Society for Testing and Materials standard quantitative carrier disk test method (ASTM E-2197-11) was used to examine the effectiveness of ultraviolet-C (UV-C) light for rapid decontamination of plastic airport security bins inoculated at 3 sites with methicillin-resistant Staphylococcus aureus (MRSA) and bacteriophages MS2, PhiX174, and Phi6, an enveloped RNA virus used as a surrogate for coronaviruses. Three log10 reductions on inoculated plastic bins were considered effective for decontamination. Results: UV-C light administered as 10-, 20-, or 30-second cycles in proximity to a plastic bin reduced contamination on each of the test sites, including vertical and horizontal surfaces.  The 30-second cycle met criteria for decontamination of all 3 test sites for all the test organisms except bacteriophage MS2 which was reduced by greater than 2 log10 PFU at each site. Conclusions: UV-C light is an attractive technology for rapid decontamination of airport security bins.  Further work is needed to evaluate the utility of UV-C light in real-world settings and to develop methods to provide automated movement of bins through a UV-C decontamination process.


mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Jared C. Nigg ◽  
Yen-Wen Kuo ◽  
Bryce W. Falk

ABSTRACT Piwi-interacting RNAs (piRNAs) are a class of small RNAs primarily responsible for silencing transposons in the animal germ line. The ping-pong cycle, the posttranscriptional silencing branch of the piRNA pathway, relies on piRNAs produced from endogenous transposon remnants to direct cleavage of transposon RNA via association with Piwi-family Argonaute proteins. In some mosquito species and mosquito-derived cell lines expressing a functionally expanded group of Piwi-family Argonaute proteins, both RNA and DNA viruses are targeted by piRNAs in a manner thought to involve direct processing of exogenous viral RNA into piRNAs. Whether viruses are targeted by piRNAs in nonmosquito species is unknown. Partial integrations of DNA and nonretroviral RNA virus genomes, termed endogenous viral elements (EVEs), are abundant in arthropod genomes and often produce piRNAs that are speculated to target cognate viruses through the ping-pong cycle. Here, we describe a Diaphorina citri densovirus (DcDV)-derived EVE in the genome of Diaphorina citri. We found that this EVE gives rise to DcDV-specific primary piRNAs and is unevenly distributed among D. citri populations. Unexpectedly, we found that DcDV is targeted by ping-pong-dependent virus-derived piRNAs (vpiRNAs) in D. citri lacking the DcDV-derived EVE, while four naturally infecting RNA viruses of D. citri are not targeted by vpiRNAs. Furthermore, a recombinant Cricket paralysis virus containing a portion of the DcDV genome corresponding to the DcDV-derived EVE was not targeted by vpiRNAs during infection in D. citri harboring the EVE. These results demonstrate that viruses can be targeted by piRNAs in a nonmosquito species independently of endogenous piRNAs. IMPORTANCE Small RNAs serve as specificity determinants of antiviral responses in insects. Piwi-interacting RNAs (piRNAs) are a class of small RNAs found in animals, and their primary role is to direct antitransposon responses. These responses require endogenous piRNAs complementary to transposon RNA. Additionally, piRNAs have been shown to target RNA and DNA viruses in some mosquito species. In contrast to transposons, targeting of viruses by the piRNA pathway in these mosquito species does not require endogenous piRNAs. Here, we show that piRNAs target a DNA virus, but not RNA viruses, in an agricultural insect pest. We found that targeting of this DNA virus did not require endogenous piRNAs and that endogenous piRNAs did not mediate targeting of an RNA virus with which they shared complementary sequence. Our results highlight differences between mosquitoes and our experimental system and raise the possibility that DNA viruses may be targeted by piRNAs in other species.


Author(s):  
Milon Mondal ◽  
Chandan Sarkar ◽  
Sarmin Jamaddar ◽  
Abul Bashar Ripon Khalipha ◽  
Muhammad Torequl Islam ◽  
...  

Background: Coronavirus disease 2019 (COVID-19) is a life intimidating viral infection caused by a positive sense RNA virus belonging to the Coronaviridae family, named severe acute respiratory distress syndrome coronavirus 2 (SARA-CoV-2). Since its outbreak in December 2019, the pandemic has spread to more than 200 countries, infected more than 26 million, and claimed the lives of more than 800,000 people. As a disease, COVID-19 can lead to severe and occasionally fatal respiratory problems in humans. Infection with this virus is associated with fever, cough, dyspnea, and muscle aches, and it may progress to pneumonia, multiple organ failure, and death. To date, there is no specific antiviral treatment against this virus. However, the main viral protease has been recently discovered and it is regarded as an appropriate target for antiviral agents in the search for treatment of COVID-19, due to its pivotal role in polyproteins processing during viral replication. Aim: Consequently, this study intends to evaluate the effectiveness of FDA-approved anti-viral drugs against SARA-CoV-2 through a molecular docking study. Methods: AutoDock Vina in PyRx platform was used for docking analysis against the main viral protease (Mpro) (PDB ID 6LU7), and Computed Atlas of Surface Topography of proteins (CASTp 3.0) was applied for detecting and characterizing cavities, pockets, and channels of this protein structure. Results: Results revealed that among the conventional antiviral drugs, the protease inhibitors, lopinavir, amprenavir, indinavir, maraviroc, saquinavir, and daclatasvir showed high binding affinity and interacted with amino acid residues of the binding site. Conclusion: In conclusion, protease inhibitors may be effective potential antiviral agents against Mpro to combat SARSCoV-2.


Sign in / Sign up

Export Citation Format

Share Document