Aug 25, 2014
03:26 PM
Connecticut Today

Ebola Drug Under Development by Connecticut Company

Ebola Drug Under Development by Connecticut Company

(Photo by John Moore/Getty Images)

A Chinese UN soldier prepares a truckload of Ebola relief aid after it was airlifted by the United Nations Children's Fund (UNICEF), on August 23, 2014 in Harbel, Liberia.

The suspected Patient Zero in the current Ebola outbreak lived in Guéckédou, in southeastern Guinea near the borders of Sierra Leone and Liberia. He first began showing strong symptoms of the virus on Dec. 2, and died just four days later. He was 2 years old.

A week after the boy’s death, the deadly disease killed his mother, then his 3-year-old sister and grandmother. Unrecognized, the virus, which has a two-to-three week incubation period, continued to spread.

Two people who attended the grandmother’s funeral took it back to their village, and spread it to relatives from other villages. A health worker contracted it and spread it to yet another village.

The virus was identified as Ebola in March but that has done little to slow the rate of contamination. To date, the disease has infected 2,473 people and resulted in 1,350 deaths.

Last week the World Health Organization said the scale of the epidemic had been vastly underestimated and "extraordinary measures" were needed to contain the disease.

"It is deteriorating faster, and moving faster, than we can respond to," MSF (Doctors Without Borders) chief Joanne Liu told reporters in Geneva according to MSN.com.

(Above: an MSF medical worker, wearing protective clothing at an MSF Ebola treatment facility in Kailahun, on August 15, 2014.  CARL DE SOUZA/AFP/Getty Images)

The region is awaiting consignments of up to 1,000 doses of the barely-tested drug ZMapp from the United States, while Canada is sending between 800 and 1,000 doses of a vaccine called VSV-EBOV, which has been effective in animals but has never been tested on humans. Results from ZMapp have been mixed, and even if either drug proves to be safe and effective, supplies are inefficient to stem the tide of the outbreak.

“This outbreak doesn't appear to be going away, it's not burning itself out,” says Dr. Eugene Seymour, an MD, MPH and CEO of NanoViricides, Inc., a small Connecticut biotech company that recently resumed its research for the development of an Ebola drug.

The move was prompted by the Ebola crisis in Africa and the fact that Seymour and scientists in the company believe they can potentially fight this disease more effectively than anyone else.

 

NanoVircicides held the grand opening for its new Shelton headquarters on July 22, and Congressman Jim Himes performed the official ribbon cutting. The new facility (below) is located in a quiet corporate park. Across the parking lot from the building there’s a small pond, and on a recent afternoon a light breeze blew off the pond, it was pleasant and gentle. It’s a world away from the chaos and the death being caused in Africa by Ebola, yet this facility could become the place where the war against the virus is won. If that happens, it will be largely thanks to Dr. Anil Diwan, chairman and president of NanoViricides, Inc.

Diwan has jet-black hair, a ready laugh, and a sometimes self-deprecating sense of humor. He started the company that ultimately grew into NanoViricides in a warehouse space in New Haven in the early ‘90s. Over the years he’s invested his own money and managed to make significant breakthroughs on a shoestring budget.

He’s also the person who came up with the technology for the nanoviricides (a term the company has trademarked), a molecular virus trap that is the basis of every drug the company is developing.

The company’s motto is “Bind, Encapsulate, Destroy,” and in a nutshell that’s how the NanoViricides work.

A virus attacks specific types of cells and hijack the host cell by injecting DNA or RNA and taking over the cell’s enzymes to create duplicates of itself. These duplicate copies of the virus then break free of the host cell and infect new cells.

“There are more viruses than you ever could count,” explains Diwan. “Every breath you take you are exposed to probably 10,000 viruses, but most of them don’t cause disease.”

Viruses can be chemically simple, yet still devastating to living hosts. Ebola is made of only ten proteins locked together, but in this recent outbreak it has killed about 60 percent of those infected. By using various attachment receptors, the Ebola virus can enter a variety of the body’s cells; it also shuts down the immune system’s defenses and gains the upper hand.

For quickly mutating viruses and viruses like Ebola (pictured at right) that can work too powerfully and fast for our bodies to handle, Diwan hopes nanoviricides will act as the cavalry charge—killing the foreign invasion quicker and more effectively than the immune system can.

Each nanoviricide consists of two parts, one is called the virus-binding ligand and the other is a nanomicelle flexible polymer. The ligand is chemically designed to match with the surface cell receptor of the virus and binds with the virus, tricking it into “thinking” the nanoviricide is a human cell and thereby trapping it. The viral materials are now being released into the nanomicelle flexible polymer, which engulfs and then destroys the virus without allowing it to reproduce. Because the surface cell receptor does not generally change, even if the virus mutates, nanoviricides seem to be an effective tool against fast-mutating strains like the flu. And because the only part of the nanoviricide that has to be changed with different diseases is the virus-binding ligand, nanoviricides to fight new diseases can be designed relatively quickly.“Did you ever see ‘Fantastic Voyage,’” asks Diwan as he explains nanoviricides. In the 1966 science fiction film, Raquel Welch is shrunk and injected into a patient’s blood stream to remove a deadly brain clot. “That’s exactly what we came up with—it’s basically a nanomachine that we’ve built.” He’s joking, but only partially.

In animal testing, the nanoviricides have proven extremely effective, arguably as effective as a mini-Raquel Welch. The company’s anti-influenza drug FluCide (which is its main focus) produced a 1,000-fold viral load reduction in animal given a lethal dose of influenza.  For comparison, Tamiflu, the leading antiviral flu drug, produced only a 2-fold reduction in the same study. FluCide is expected to begin human trials before the end of next year. However, that projected time is dependent on the timely completion of the toxicology studies that will be performed by BASi, Inc, an international provider of toxicology studies. The company is also working on many different nanoviricides, for example, developing drugs to combat herpes and HIV--aamazingly, with the latter (explained in the diagram above), animal tests suggest the treatment could create a “functional cure” of HIV-infected patients. 

Despite being referred to as “nanomachines” by Diwan and others in the company, nanoviricides are in fact chemical substances and have toxicity levels lower than most other drugs.

“It has nothing mechanical. It basically becomes food to the body after the job,” Diwan says.

Seymour, the CEO of the company, says the technology they are developing is particularly well-equipped to handle a new and unexpected viral outbreak such as the current Ebola one.

“For us to make a new drug all we have to do is look at the nature of the receptor protein on the surface of the host cell of the virus,” he says, ”Once that’s done an effective drug can be manufactured quickly. It's pretty remarkable stuff.”

Diwan adds, “Although most viruses use specialized receptors, there are a few common receptors that are used by 95-99 percent of viruses, at least for initial binding. We have developed a library of ligands based on these receptors. This library can be tested against the novel virus and the most effective ones can be used for treatment. If the specialized receptor is known, we can develop more specialized appropriate ligands, and nanoviricide drug candidates, based on that information.”

But with Ebola there’s a catch. The virus produces a protein decoy that confuses the immune system’s response and could potentially stop nanoviricides from binding with it. When Diwan was approached about working with Ebola years ago he thought the decoy would render his treatment ineffective. Now he think’s he’s got a way to overcome the decoy.

 

Ebola first appeared in humans in 1976 in two simultaneous outbreaks, in Nzara, Sudan, and in Yambuku, Democratic Republic of Congo. The latter outbreak occurred in a village near the Ebola River, which gives the disease its name. It caused 288 deaths and had an 88 percent fatality rate, one of the highest ever reported for a human virus.

(Left: an MSF medical worker, wearing protective clothing at an MSF Ebola treatment facility in Kailahun, on August 15, 2014. CARL DE SOUZA/AFP/Getty Images)

Over the years different strains of Ebola have caused other outbreaks. Many were small, including a 1989 scare that occurred in the U.S. when Ebola-Reston virus was introduced into quarantine facilities in Virginia and Pennsylvania by monkeys imported from the Philippines. Other flare-ups claimed the lives of hundreds of patients before they burnt out, but none have came close to approaching the scale of the current outbreak.

Scientists are uncertain how patient zero contracted this strain of the virus. In the past, Ebola has spread to humans when they’ve come in contact with infected animal fluids or tissue. A report on the outbreak published in the New England Journal of Medicine notes the region where the virus began is home to many fruit bat species, “potential reservoirs” of the virus (in biological terms, a reservoir is any species that can host and transmit the virus).

Richard Preston, author of the classic nonfiction book The Hot Zone which is about Ebola and similar viruses, recently wrote that “when Ebola strikes a human it becomes a killing machine, the biological equivalent of a steel axe.”

It is called a filovirus because it resembles a strand of string. It causes deadly hemorrhagic fever characterized by gruesome symptoms: vomiting, diarrhea, uncontrolled bleeding and possible organ failure. In the New Yorker article that inspired The Hot Zone, Preston wrote about the strange and horrifying effects the virus can have on people:

A classic sign of infection by Ebola…is a certain expression that invariably creeps over the patient’s face as the infection progresses. The face becomes fixed and “expressionless,” “masklike,” “ghostlike” (in the words of doctors who have seen it), with wide, deadened, “sunken” eyes. The patient looks and sometimes behaves like a zombie. This happens because Ebola damages the brain in some way that isn’t known. The classic masklike facial expression appears in all primates infected with Ebola, both monkeys and human beings. They act as if they were already embalmed, even though they are not yet dead. The personality may change: the human patient becomes sullen, hostile, agitated, or develops acute psychosis. Some have been known to escape from the hospital.

 

Diwan is a graduate of the Indian Institute of Technology in Mumbai and Ph. D recipient from Rice University, Texas. He first began exploring the idea of nanoviricides in the early 1990s. He was inspired to pursue this technology after seeing the shortcomings of gene therapy, a new and popular form of treatment at the time. (In gene therapy, DNA is injected into patients through viruses in order to introduce a new gene into the body to fight a disease, inactivate an existing gene, or replace a mutated gene. The problem is the treatment is difficult to control, the viral vectors used to insert the new DNA can be toxic, and the new gene can cause harmful mutations.)

Working out of a small space in New Haven, Diwan began developing the concept of nanoviricides, which he felt could have the same effect as gene therapy without the negative side effects. Initially he was looking at treating cancer but over time he shifted his focus to viruses.

Through the ‘90s he operated under the auspices of a couple of small companies he had formed. In 2003, he got in touch with Seymour, the company’s current CEO. Seymour is a successful biotech entrepreneur; during the 1980s while practicing as a physician in Los Angeles he began treating the first waves of HIV patients. Seeing that in the absence of a cure, prevention was critical he developed the Hema-Strip blood test for the virus, which would become an important HIV test. About a year after Seymour was contacted by Diwan, he agreed to meet with him so Diwan could present and pitch his concept.

They decided to meet in New York City at a Kosher deli. On his way to the meeting, Diwan didn’t plan for traffic and got stuck for hours on the FDR Drive. He arrived after 8 p.m. for what had been planned as a 4 p.m. meeting. The deli was closing, Seymour was about to leave but agreed to stay and let Diwan pitch him the idea—the only problem was in Diwan’s rush to get there he had left all his materials in the car. With the future of his concept potentially on the line, Diwan had no choice but to improvise. He grabbed a crumpled deli napkin and began to draw out the basic concept of the nanoviricides. Despite the unorthodox presentation, what Seymour saw on that napkin impressed him and he decided to join forces with Diwan.

In 2005, the company, NanoViricides, Inc., was officially formed, and merged into a public shell to become a publicly traded company on the pink sheets. Soon thereafter, the company filed the paperwork with the U.S. Securities and Exchange Commission to become a reporting company and in 2007, started trading on the OTC bulletin board. Last September NanoViricides uplisted on the New York Stock Exchange (NYSE MKT: NNVC). The company’s new Shelton location has a large lab and a suite of state-of-the-art “clean rooms” (pictured above) where drugs can be manufactured under extremely sterile conditions. Before entering the main clean room suite, workers have to shower, then go through a series of three airlock rooms. Each room has an air shower and some require a new change of clothes. (Walking through this gauntlet of disinfection feels like stepping onto the set of a science fiction flick.)

At this facility Diwan hopes he’ll eventually be able to manufacture a drug that can defeat Ebola. Shortly after Diwan was approached about Ebola in 2005, interest and funding for research dried up and NanoViricides Inc. shelved research on an Ebola drug. But when the current Ebola outbreak began and showed no signs of slowing down, the company decided to restart research on that drug.

Today, Diwan believes he’s come up with a way to overcome the virus’ decoy. Step one will be adding an extra viral receptor mimicking ligand to the nanoviricides designed to overcome the virus’ decoy, and step two will be upping the dosage of the drug—because the drug’s toxicity is so low there’s no danger in doing this and the increased dosage will help make treatment effective even if some nanoviricides are taken up in defeating the decoy.

Diwan believes this drug could be more effective than any of the experimental Ebola drugs currently being sent to the region. And unlike those drugs, Diwan’s drug is not expected to have adverse side effects. Plus, his company has the capability at its Shelton facility to produce it in great enough numbers to handle an outbreak. More importantly, because the nanoviiricide is “broad-spectrum” drug, it is expected to work against all versions of Ebola, unlike the other experimental drugs.

The only problem is the concept for the Ebola nanoviricides can’t be tested readily. Diwan’s company conducts all animal and live-disease testing offsite. With Ebola this becomes complicated. There are only a handful of labs in the world with active strains of the virus, and these labs are currently overwhelmed because of the outbreak.

When Ebola is brought under control, or possibly if it continues to spiral out of control and the world gets desperate, Diwan’s drug will be tested. NanoViricides has connected with the US Army Medical Research Institute for Infectious Diseases (USAMRIID) as well as the National Institutes of Health facility (both in Maryland), and they are working out a plan for Ebola drug testing. If the drug is successful, manufacturing could begin in Connecticut.

If that day ever comes, Diwan believes the horrifying Ebola virus will be destroyed, and the Connecticut Company’s motto, “Bind, Encapsulate, Destroy” will ring true. 

Contact me by email eofgang@connecticutmag.com and follow me on Twitter, and connect with Connecticut Magazine on Twitter, on Facebook and Google +

Ebola Drug Under Development by Connecticut Company

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