Inhibitory effects of bee venom and its components against viruses in vitro and in vivo. - PubMed - NCBI

 Bee venom (BV) from honey bee (Apis Melifera L.) contains at least 18 pharmacologically active components including melittin (MLT), phospholipase A2 (PLA2), and apamin etc. BV is safe for human treatments dose dependently and proven to possess different healing properties including antibacterial and antiparasitidal properties. Nevertheless, antiviral properties of BV have not well investigated. Hence, we identified the potential antiviral properties of BV and its component against a broad panel of viruses. Co-incubation of non-cytotoxic amounts of BV and MLT, the main component of BV, significantly inhibited the replication of enveloped viruses such as Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Respiratory Syncytial Virus (RSV), and Herpes Simplex Virus (HSV). Additionally, BV and MLT also inhibited the replication of non-enveloped viruses such as Enterovirus-71 (EV-71) and Coxsackie Virus (H3). Such antiviral properties were mainly explained by virucidal mechanism. Moreover, MLT protected mice which were challenged with lethal doses of pathogenic influenza A H1N1 viruses. Therefore, these results provides the evidence that BV and MLT could be a potential source as a promising antiviral agent, especially to develop as a broad spectrum antiviral agent.



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Viruses transfer the antiviral second messenger cGAMP between cells

 "Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING). We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. Virions transferred cGAMP to newly infected cells and triggered a STING-dependent antiviral program. These effects were independent of exosomes and viral nucleic acids. Our results reveal a way by which a signal for innate immunity is transferred between cells, potentially accelerating and broadening antiviral responses. Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation. Loading viral vectors with cGAMP therefore holds promise for vaccine development."

Endocannabinoid CB1 antagonists inhibit hepatitis C virus production, providing a novel class of antiviral host targeting agents.

Direct acting antivirals have significantly improved treatment outcomes
in chronic hepatitis C (CHC), but side effects, drug resistance and cost
mean that better treatments are still needed. Lipid metabolism is
closely linked with hepatitis C virus (HCV) replication and
endocannabinoids are major regulators of lipid homeostasis. The
cannabinoid 1 (CB1) receptor mediates these effects in the liver. We
have previously shown up-regulation of CB1 receptors in the livers of
patients with CHC, and in a HCV cell culture model. Here we investigated
whether CB1 blockade inhibits HCV replication. The antiviral effect of a
CB1 antagonist, AM251 was examined in the JFH1 cell culture and
subgenomic replicon models. The effects on the expression of genes
involved in lipid metabolism were also measured. CB1 shRNA was used to
confirm that the effects were specific for the cannabinoid receptor.
Treatment with AM251 strongly inhibited HCV RNA (~70%), viral protein
(~80%), the production of new virus particles (~70%), and virus
infectivity (~90%). As expected, AM251 reduced the expression of
pro-lipogenic genes (SREBP-1c, FASN, SCD1 and ACC1) and stimulated genes
promoting lipid oxidation (CPT1 and PPARα). This effect was mediated by
AMPK. Stable CB1 knockdown of cells infected with HCV showed reduced
levels of HCV RNA, compared with controls. Reduced CB1 signalling
inhibits HCV replication using either pharmacological inhibitors or CB1
shRNA. This may be due, at least in part, to reduced lipogenesis,
mediated by AMPK activation. We suggest that CB1 antagonists may
represent an entirely new class of drugs with activity against HCV.

CDK9 inhibitor FIT-039 prevents replication of multiple DNA viruses.

A wide range of antiviral drugs is currently available; however,
drug-resistant viruses have begun to emerge and represent a potential
public health risk. Here, we explored the use of compounds that inhibit
or interfere with the action of essential host factors to prevent virus
replication. In particular, we focused on the cyclin-dependent kinase 9
(CDK9) inhibitor, FIT-039, which suppressed replication of a broad
spectrum of DNA viruses through inhibition of mRNA transcription.
Specifically, FIT-039 inhibited replication of herpes simplex virus 1
(HSV-1), HSV-2, human adenovirus, and human cytomegalovirus in cultured
cells, and topical application of FIT-039 ointment suppressed skin
legion formation in a murine HSV-1 infection model. FIT-039 did not
affect cell cycle progression or cellular proliferation in host cells.
Compared with the general CDK inhibitor flavopiridol, transcriptome
analyses of FIT-039-treated cells revealed that FIT-039 specifically
inhibited CDK9. Given at concentrations above the inhibitory
concentration, FIT-039 did not have a cytotoxic effect on mammalian
cells. Importantly, administration of FIT-039 ameliorated the severity
of skin lesion formation in mice infected with an acyclovir-resistant
HSV-1, without noticeable adverse effects. Together, these data indicate
that FIT-039 has potential as an antiviral agent for clinical
therapeutics.

PLOS ONE: Alzheimer's Associated β-Amyloid Protein Inhibits Influenza A Virus and Modulates Viral Interactions with Phagocytes

Accumulation of β-Amyloid (βA) is a key pathogenetic factor in
Alzheimer's disease; however, the normal function of βA is unknown.
Recent studies have shown that βA can inhibit growth of bacteria and
fungi. In this paper we show that βA also inhibits replication of
seasonal and pandemic strains of H3N2 and H1N1 influenza A virus (IAV)
in vitro. The 42 amino acid fragment of βA (βA42) had greater activity
than the 40 amino acid fragment. Direct incubation of the virus with
βA42 was needed to achieve optimal inhibition. Using quantitative PCR
assays βA42 was shown to reduce viral uptake by epithelial cells after
45 minutes and to reduce supernatant virus at 24 hours post infection.
βA42 caused aggregation of IAV particles as detected by light
transmission assays and electron and confocal microscopy. βA42 did not
stimulate neutrophil H₂O₂ production or
extracellular trap formation on its own, but it increased both responses
stimulated by IAV. In addition, βA42 increased uptake of IAV by
neutrophils. βA42 reduced viral protein synthesis in monocytes and
reduced IAV-induced interleukin-6 production by these cells. Hence, we
demonstrate for the first time that βA has antiviral activity and
modulates viral interactions with phagocytes.

Related articles

• The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide.
  
  • Acyclovir or Aβ42 peptides attenuate HSV-1-induced miRNA-146a levels in human primary brain cells.

A mini-antibody with broad antiviral activity chews up viral DNA and RNA - Medical News Today

Antibodies and their derivatives can protect plants and animals -
including humans - against viruses. Members of this class of drugs are
usually highly specific against components of a particular virus, and
mutations in the virus that change these components can make them
ineffective. An article published in PLOS Pathogens now reports
that a mini antibody called 3D8 scFv can degrade (or chew up) viral DNA
and RNA regardless of specific sequences and protect mammalian cells
and genetically manipulated mice against different viruses.

Plos Pathogens

A Nucleic-Acid Hydrolyzing Single Chain Antibody Cnfers Resistance to DNA Virus Infection in HeLa Cells and C57BL/6 Mice

Related articles

• Possible Universal Flu Vaccine made from Messenger RNA (nextbigfuture.com)

Mammals Defend Against Viruses Differently than Invertebrates

Biologists have long wondered if mammals share the elegant system used by insects, bacteria and other invertebrates to defend against viral infection. Two back-to-back studies in the journal Science last year said the answer is yes, but a study just published in Cell Reports by researchers at the Icahn School of Medicine at Mount Sinai found the opposite.

In the Mount Sinai study, the results found that the defense system used by invertebrates—RNA interferences or RNAi—is not used by mammals as some had argued. RNAi are small molecules that attach to molecular scissors used by invertebrates to cut up invading viruses.

Mammals use a form of RNAi to fine-tune the expression of hundreds of genes that coordinate development in the womb, says the study’s senior author, Benjamin tenOever, PhD, Fishberg Professor in the Department of Medicine and Department of Microbiology at the Icahn School of Medicine at Mount Sinai. But it has never been clear that adult mammals use RNAi the same way that plants and insects do, he says. “Mammals have cell machinery that looks capable of producing RNAi to fight virus, but we believe it only helps to produce different small RNA products called microRNAs, which are not antiviral,” Dr. tenOever says.

Related articles

• Innate virus-killing power discovered in mammals (sciencedaily.com)
• Mammals chop up viral RNA to attack infection (nature.com)

A small molecule inhibits virion attachment to heparan sulfate- or sialic acid-containing glycans.

Primary attachment to cellular glycans is a critical entry step for most human viruses. Some viruses, such as herpes simplex virus type 1 (HSV-1) and hepatitis C virus (HCV), bind to heparan sulfate, whereas others, such as influenza (IAV), bind to sialic acid. Receptor mimetics that interfere with these interactions are active against viruses that bind to either heparan sulfate or to sialic acid. However, no molecule that inhibits the attachment of viruses in both groups has yet been identified. Epigallocatechin gallate (EGCG), a green tea catechin, is active against many unrelated viruses, including several that bind to heparan sulfate or to sialic acid. We sought to identify the basis for the broad-spectrum activity of EGCG. Here, we show that EGCG inhibits the infectivity of a diverse group of enveloped and nonenveloped human viruses. EGCG acts directly on the virions, without affecting the fluidity or integrity of the virion envelopes. Instead, EGCG interacts with virion surface proteins to inhibit the attachment of HSV-1, HCV, IAV, vaccinia virus, adenovirus, reovirus and vesicular stomatitis virus (VSV) virions. We further show that EGCG competes with heparan sulfate for binding of HSV-1 and HCV virions, and with sialic acid for binding of IAV virions. Therefore, EGCG inhibits unrelated viruses by a common mechanism. Most importantly, we have identified EGCG as the first broad-spectrum attachment inhibitor. Our results open the possibility for the development of small molecule broad-spectrum antivirals targeting virion attachment.
IMPORTANCE.:

This study shows that it is possible to develop a small molecule antiviral or microbicide active against the two largest groups of human viruses, those that bind to glycosaminoglycans and those that bind to sialoglycans. This group includes the vast majority of human viruses, including herpes simple viruses, cytomegalovirus, influenza virus, poxvirus, hepatitis C virus, HIV, and many others.

Tranylcypromine Reduces Herpes Simplex Virus 1 Infection in Mice.

Herpes simplex virus 1 (HSV-1)
infects the majority of the human population and establishes latency by
maintaining viral genomes in neurons of sensory ganglia. Latent virus
can undergo reactivation to cause recurrent infection. Both primary and
recurrent infections can cause devastating diseases, encephalitis and
corneal blindness. Acyclovir is used to treat patients, but virus
resistance to acyclovir is frequently reported. Recent in vitro findings
reveal that pretreatment of cells with tranylcypromine (TCP), the drug
widely used in the clinic to treat neurological disorders, restrains HSV-1
gene transcription by inhibiting the histone modifying enzyme,
lysine-specific demethylase-1. The present study was designed to examine
the anti-HSV-1
efficacy of TCP in vivo because of the paucity of reports on this
issue. Using the murine model, we found that TCP decreased the severity
of wild-type virus-induced encephalitis and corneal blindness, the
infection of acyclovir-resistant (thymidine kinase-negative) HSV-1
mutant, and tissue viral loads. Additionally, TCP blocked in vivo viral
reactivation in trigeminal ganglia. These results support the
therapeutic potential of TCP for controlling HSV-1 infection.

Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol.

Interferons (IFN) are essential antiviral cytokines that establish the cellular antiviral state through upregulation of hundreds of interferon-stimulated genes (ISGs), most of which have uncharacterized functions and mechanisms. We identified cholesterol-25-hydroxylase (CH25H) as a broadly antiviral ISG. CH25H converts cholesterol to a soluble antiviral factor, 25-hydroxycholesterol (25HC). 25HC treatment in cultured cells broadly inhibited growth of enveloped viruses including VSV, HSV, HIV, and MHV68 and acutely pathogenic EBOV, RVFV, RSSEV, and Nipah viruses under BSL4 conditions. It suppressed viral growth by blocking membrane fusion between virus and cell. In animal models, Ch25h-deficient mice were more susceptible to MHV68 lytic infection. Moreover, administration of 25HC in humanized mice suppressed HIV replication and reversed T cell depletion. Thus, our studies demonstrate a unique mechanism by which IFN achieves its antiviral state through the production of a natural oxysterol to inhibit viral entry and implicate membrane-modifying oxysterols as potential antiviral therapeutics.

Antiviral enzyme contributes to several forms of cancer

The discovery, reported in the July 14 issue of Nature Genetics, follows the team's earlier finding that the enzyme, called APOBEC3B, is responsible for more than half of breast cancer cases. The previous study was published in Nature in February.

APOBEC3B is part of a family of antiviral proteins that Harris has studied for more than a decade. His effort to understand how these proteins work has led to these surprising discoveries that APOBEC3B is a broadly important cancer mutagen

Exosomes mediate the cell-to-cell transmission of IFN-[alpha]-induced antiviral activity : Nature Immunology

The cell-to-cell transmission of viral resistance is a potential mechanism for amplifying the interferon-induced antiviral response. In this study, we report that interferon-α (IFN-α) induced the transfer of resistance to hepatitis B virus (HBV) from nonpermissive liver nonparenchymal cells (LNPCs) to permissive hepatocytes via exosomes. Exosomes from IFN-α-treated LNPCs were rich in molecules with antiviral activity. Moreover, exosomes from LNPCs were internalized by hepatocytes, which mediated the intercellular transfer of antiviral molecules. Finally, we found that exosomes also contributed to the antiviral response of IFN-α to mouse hepatitis virus A59 and adenovirus in mice. Thus, we propose an antiviral mechanism of IFN-α activity that involves the induction and intercellular transfer of antiviral molecules via exosomes.

Toward broad-spectrum antiviral drugs for common cold and other infections

"Scientists are reporting progress in the search for the first broad-spectrum drugs to combat human rhinoviruses (HRVs), which cause humanity's most common infectious diseases. Their study on these potential drugs for infections that include the common cold appears in the journal ACS Medicinal Chemistry Letters."

Retinazone inhibits certain blood-borne human viruses including Ebola virus Zaire.

Human hepatitis B and immunodeficiency viruses integrate their retro-transcribed DNA proviruses into the human host genome. Existing antiretroviral drug regimens fail to directly target these intrachromosomal xenogenomes, leading to persistence of viral genetic information. Retinazone (RTZ) constitutes a novel vitamin A-derived (retinoid) thiosemicarbazone derivative with broad-spectrum antiviral activity versus human immunodeficiency, hepatitis C, varicella-zoster and cytomegalo-viruses.

METHODS:

The in vitro inhibitory action of RTZ on HIV-1 strain LAI, human hepatitis B virus strain ayw, HCV-1b strain Con1, enhanced green fluorescent protein-expressing Ebola virus Zaire 1976 strain Mayinga, wild-type Ebola virus Zaire 1976 strain Mayinga, human herpesvirus 6B and Kaposi's sarcoma-associated herpesvirus replication was investigated. The binding of RTZ to human glucocorticoid receptor was determined.

RESULTS:

RTZ inhibits the bloodborne human hepatitis B virus multiplication in vitro by covalent inactivation of intragenic and intraexonic viral glucocorticoid response elements, and, in close analogy, RTZ suppresses HIV-1 multiplication in vitro. RTZ disrupts the multiplication of the bloodborne human hepatitis C and Ebola Zaire viruses at nanomolar concentrations in vitro. RTZ has the capacity to bind to human glucocorticoid receptor, to selectively and covalently bind to intraexonic viral glucocorticoid response elements, and thereby to inactivate human genome-integrated proviral DNA of human hepatitis B and immunodeficiency viruses.

CONCLUSIONS:

RTZ represents the first reported antiviral agent capable of eradicating human immunodeficiency and hepatitis B proviruses from their human host. Furthermore, RTZ represents a potent and efficacious small-molecule in vitro inhibitor of Ebola virus Zaire 1976 strain Mayinga replication.

Researchers find potential novel treatment for influenza

 "The scientists found that a drug called Eritoran ( a Toll receptor antagonist (TLR4) )can protect mice from death after they have been infected with a lethal dose of influenza virus. The potential value of this drug as single therapy or in combination with antivirals is further supported by previous research that found that it is safe for use in humans. The findings are of particular interest to scientists now that the latest deadly strain of flu, H7N9, is spreading in China – 82 people in China had been infected with the new strain of flu virus as of April 26, and 17 had died."

Chemical compounds that halt virus replication identified

"In this study, researchers identified a new chemical class of compounds that effectively blocked genetically diverse viruses from replicating by limiting RNA production by the virus in cell culture. These indoline alkaloid-type compounds inhibited a number of viruses from replicating, including Ebola."

Paper in Chemistry and Biology:-

Identification of a broad-spectrum inhibitor of virus RNA synthesis: validation of a prototype virus-based approach. 

Antiviral lipid earns patent: Lipids in lung can inhibit RSV and influenza infections

 "Dennis Voelker, PhD, professor of medicine at National Jewish Health, has been awarded a U.S. patent (#8,367,643) for various lipids and related compounds that can inhibit inflammation and infection in the lungs, especially those caused by influenza and respiratory syncytial virus (RSV). Over the past several years, Dr. Voelker has published several scientific papers describing a naturally occurring lipid in the lungs, POPG (palmitoyl-oleoyl-phosphatidylglycerol), that reduces inflammation and inhibits infection by the influenza virus and RSV. The patent covers POPG and other naturally occurring lipids in the lungs as well as related anionic lipids."

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Newly identified natural protein (cholesterol-25-hydroxylase) blocks HIV, other deadly viruses / UCLA Newsroom

In a study published in the January issue of the journal Immunity, the researchers describe the novel antiviral property of the protein, cholesterol-25-hydroxylase (CH25H), an enzyme that converts cholesterol to an oxysterol called 25-hydroxycholesterol (25HC), which can permeate a cell's wall and block a virus from getting in.

Valine, a branched-chain amino Acid, reduced HCV viral load and led to eradication of HCV by interferon therapy in a decompensated cirrhotic patient.

A decreased serum level of branched-chain amino acid (BCAA) is a distinctive metabolic disorder in patients with liver cirrhosis. Recently, BCAA has been reported to exert various pharmacological activities, and valine, which is a BCAA, has been shown to affect lipid metabolism and the immune system in in vivo experiments. However, the clinical impact of valine supplementation on viral hepatitis C virus (HCV) load has never been reported. Here, we first describe a case of HCV-related advanced liver cirrhosis that was treated by an oral valine agent. The administration of valine resulted in an improvement of fatigue and a reduction in hepatic fibrosis indexes as well as serum α-fetoprotein level. Furthermore, a marked reduction in HCV RNA levels was seen after valine treatment. The patient was then treated by interferon β, resulting in the successful eradication of chronic HCV infection. Thus, valine may be involved in the reduction of HCV viral load and could support a sustained virologic response to interferon therapy.