Rattlesnake venom for Hepatitis C treatment

A group of Brazilian scientists has achieved promising results using isolated compounds from the venom of the South American rattlesnake to combat hepatitis C. The investigation was based on records in scientific literature in which animal venom showed activity against some viruses, such as yellow fever, measles and dengue, which belongs to the same Flaviviridae virus family as hepatitis.
There is a great need for new methods in the fight
hepatitis C.

The researchers tested three compounds from the venom of Crotalus durissus terrificus rattlesnake, and also investigated the antiviral potential of flavonoids extracted from Pterogyne nitens, a kind of plant endemic to Brazil. Results from these experiments were published in PloS One and Scientific Reports , respectively. In the Laboratory of Toxicology at FCF-USP, two proteins from the rattlesnake venom were successfully isolated: phospholipase A2 (PLA2-CB) and crotapotin (CP).

They are found in nature as subunits of the crotoxin protein complex, which the researchers also tested. In a series of in vitro experiments with cultured human cells , they tested the antiviral action of the two compounds, both separately and together in the protein complex. They observed the compounds' effects on human cells (to prevent infection by the virus ) and directly on hepatitis C virus. The hepatitis C virus genome consists of a single strand of RNA (ribonucleic acid), which is a simple chain of nucleotides encoding the proteins in the virus.

This virus invades the human host cell to replicate, producing new viral particles. Inside the host cell, the virus produces a complementary strand of RNA, from which molecules of viral genome will emerge to constitute the new particles. The research showed that phospholipase can intercalate into double-stranded RNA, a virus replication intermediate, inhibiting the production of new viral particles. Intercalation reduced these by 86 percent compared with their production in the absence of phospholipase." When the same experiment was performed using crotoxin, production of viral particles fell 58 percent.

The second stage of the research consisted of verifying whether the compounds blocked the virus's entry into cultured human cells. In this case, the results were even more satisfactory: Phospholipase blocked 97 percent of viral cell entry, and crotoxin reduced viral infection by 85 percent.

Lastly, they tested crotapotin, another compound isolated from the same rattlesnake's venom. Crotapotin had no inhibitory effect on viral entry or replication, but did affect another stage of the virus's life cycle, reducing the release of new viral particles from cells by 78 percent. Treatment with crotoxin achieved 50 percent inhibition of viral release. According to the researchers, the results of the experiments show that phospholipase and crotapotin produced better results when used separately than together.

Substances derived from Brazilian flora: sorbifolin and pedalitin, both flavonoids isolated from the leaves of Pterogyne nitens during the experiments conducted by Professor Luis Octávio Regasini at UNESP's Green & Medicinal Chemistry Laboratory in Sao José do Rio Preto. Flavonoids are compounds found in fruit, flowers, vegetables, honey and wine. As with the compounds isolated from rattlesnake venom, the flavonoids were tested for antiviral action in human cells infected with hepatitis C virus and in uninfected cells. "Sorbifolin blocked viral entry into human cells in 45 percent of cases, while pedalitin provided more promising results, blocking entry in 79 percent of cases.

The experiment was performed with two genotypes of hepatitis C virus: genotype 2A, the standard type in all studies, and genotype 3, the second most prevalent in Brazil. In both cases, the antiviral action of the flavonoids was equivalent. At the other end of the viral life cycle, the flavonoids had no effect on viral particle replication and did not prevent their release from infected cells. The flavonoids from P. nitens are among some 200 tested compounds isolated from Brazilian plants or synthesized using natural structures. The two flavonoids were tested against hepatitis C virus because they'd been shown to have antiviral action in experiments with dengue virus.
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Repurposed drug effective for Zika virus

In both cell cultures and mouse models, a drug used to treat Hepatitis C effectively protected and rescued neural cells infected by the Zika virus and blocked transmission of the virus to mouse fetuses. Researchers at University of California San Diego School of Medicine, with colleagues in Brazil and elsewhere, say their findings support further investigation of using the repurposed drug as a potential treatment for Zika-infected adults, including pregnant women.

 Zika infection during the first trimester confers the greatest risk of congenital microcephaly. Outbreaks of Zika virus in Brazil in 2015 and 2016 were marked by an increased incidence of newborns with congenital malformations, most notably undersized heads (microcephaly) and significant neurological abnormalities.

A great deal of research has focused on the pathology of Zika infections, including earlier work by the Muotri lab and collaborators that described how the virus is transmitted from mother to fetus by infecting cells that, ironically, will later develop into the brain's first and primary form of defense against invasive pathogens.

In its latest work, however, the Muotri lab sought clinical solutions. The team investigated an antiviral drug called sofosbuvir, approved and marketed under the brand name Sovaldi to treat and cure hepatitis C infections. The drug works by inhibiting replication of the hepatitis C virus; researchers noted that both hepatitis C and Zika belong to the same viral family and bore strong structural similarities that could make sofosbuvir effective against the latter. In addition, it had been reported that sofosbuvir was protective against Zika in different cell types.

In tests using human neural progenitor cells (NPCs)-self-renewing, multipotent cells that generate neurons and other brain cell types-the scientists found that exposure to sofosbuvir not only rescued dying NPCs infected with the Zika virus, but restored gene expression linked to their antiviral response. In subsequent tests using an immunodeficient mouse model infected by Zika, intravenous injections of sofosbuvir significantly reduced viral loads in blood serum compared to a placebo group.

Fetuses of Zika-infected pregnant mice did not show detectable Zika virus amplification in the sofosbuvir-treated group. This shows that the drug was well-tolerated by the Zika-infected pregnant mice and that it was able to arrest Zika replication in vivo and stop transmission from mother to fetus.
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How hepatitis C hides in the body

The Hepatitis C (HCV) virus is invisible to the immune system by breaking down communication between the immune cells, it builds virus factories that multiply easily. It takes one to three months from infection to disease, it can lead to liver failure and death. Hepatitis C virus is transmitted through blood and infects the cells in the liver, it is difficult to detect because it does not have symptoms when you get infected.

The virus causes chronic infection that lasts a lifetime. It may take decades before the infection leads to liver failure or cancer, so a lot of people are unaware that they have the virus in their body. They only notice it when they get seriously ill, which may be too late for the treatments that are available. Hepatitis C virus destroys important proteins in the immune system to promote its own growth. The ability to directly manipulate their host cells is the reason some viruses are very harmful to human.

Human cells have a complex inner structure that is divided into different areas, with different sacs that are formed from fatty membranes. Viruses that have the same genetic material as HCV (positively polarized single-stranded RNA) cause major changes in these membrane sacs.

Liver cells infected with HCV had altered membrane sacs. To study whether the IRGM protein caused the changes, researchers employed the CRISPR-Cas system, a technique that is used for regulating cells, in this case to turn off the IRGM protein in the liver cells. When the IRGM is removed from the liver cells, the virus is unable to grow.

The reason for this is that the hepatitis C virus utilizes some of the cells, called the Golgi apparatus, where the protein IRGM has an important function. The Golgi apparatus is a kind of transport centre in the cells. It packs proteins into small sacs called vesicles and sends them where they need to go within the cell, or out to other cells.

The hepatitis C virus utilizes this to build its virus factories by taking over and redirecting these vesicles with the necessary building blocks to the site where the factories are being built. These vesicles are rich in lipids that the virus is entirely dependent on to anchor its factory construction.

When this protein is removed, the virus is no longer able to infiltrate the Golgi apparatus and thus it can't build up its secret network of virus factories. Hepatitis C is transmitted via the blood. Infection is spread primarily through unclean syringes, non-sterilized medical devices, or unsafe blood transfusions.
HVC can also be passed on from mother to child, and through bodily fluids.
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Vosevi drug for hepatitis treatment

Hepatitis C is a viral infection that can cause inflammation and serious damage to the liver. The virus is spread through human contact with infected blood.

The U.S. Food and Drug Administration (FDA) has approved Vosevi (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) tablets, a single-tablet regimen for the treatment of adults with chronic hepatitis C virus (HCV).

Vosevi is a prescription medicine used to treat adults with chronic (lasting a long time) hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis who have:
genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor.

Do not combine Vosevi with any medicines that contain rifampin (Rifater, Rifamate, Rimactane, Rifadin).
Before taking Vosevi

The drug can cause serious side effects, like: Hepatitis B virus (HBV) reactivation, slow heart rate, fainting,
dizziness, shortness of breath, chest pains, confusion, memory problems, headache, tiredness, diarrhea, and nausea.
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