Sumit Chanda Archives - Sanford Burnham Prebys
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A scientist’s perspective on the coronavirus (COVID-19) pandemic

AuthorMonica May
Date

March 17, 2020

Infectious disease expert Sumit Chanda tells us how his team is combating the virus, and the advice he gives his loved ones.

Since the first case of coronavirus (COVID-19) was identified in December 2019, the respiratory virus has swept across the globe. Cases have been confirmed on every continent but Antarctica, prompting the World Health Organization to declare COVID-19 an official pandemic.

As the world grapples with the ongoing outbreak, we spoke with Sumit Chanda, PhD, an infectious disease expert and director of Sanford Burnham Prebys’ Immunity and Pathogenesis Program, to get his perspective on the pandemic and learn what Sanford Burnham Prebys scientists are doing to find effective treatments for COVID-19.

What is coronavirus?
Coronaviruses are a large family of viruses common in animals, but they can leap to humans, causing illnesses ranging from a common cold to severe respiratory diseases such as pneumonia, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS).

Were you surprised by the virus’s rapid spread? Why or why not? 
Once there was evidence of person-to-person transmission outside of China, the rapid global spread of the virus was not surprising. Since this is a new virus, there is no natural immunity in the human population to slow the spread of the pathogen. Furthermore, respiratory viruses are among the most easily spread microbes and thus considered to have high pandemic potential.

Is there a vaccine for COVID-19?
Since this is a new coronavirus, there is no vaccine—and developing one can take several years.

How are Sanford Burnham Prebys scientists working to combat COVID-19? 
As we speak, our scientists are looking to find known drugs that can inhibit the virus. Typically, it can take five to 10 years to bring a new drug to the market. However, the approach we are taking at Sanford Burnham Prebys, known as drug repositioning, can cut this development time dramatically. Since we are looking at FDA-approved drugs that are proven to be safe in humans, these medicines could rapidly get to people infected with the virus. If successful, drug repositioning will likely be the fastest path to find a therapeutic solution for the virus. 

Longer term, work has been ongoing to develop broad-spectrum antivirals. These medicines would work against many viruses, not just one. For example, if we had developed a broad-spectrum antiviral that works on MERS or SARS, it is likely it could be used for the current COVID-19 outbreak. Ideally, the therapy could be given prophylactically to block the rapid spread of the disease.

What are the benefits of drug repositioning? 
Drug repositioning is advantageous because FDA-approved drugs have already completed safety testing—meaning they have been used in people and are known to be safe. Safety testing can take years to complete. This means that if we do find a therapy that is effective against COVID-19, we can bring it to patients much faster than a novel treatment. 

Get an inside look at the race to find a treatment for COVID-19.

Any predictions for how far the virus will spread in the U.S.? 
We eagerly await large-scale testing for the virus so we can get a better understanding of how widespread it currently is in the U.S. It is difficult to predict a potential trajectory of viral spread in the U.S. until those numbers become available. 

But as of now, I have not seen any evidence of disease containment. It will be instructive to see how the situation plays out in other advanced democracies that are coping with a viral outbreak, including South Korea and Europe, to get a better idea of what might happen here.

What advice are you giving your loved ones?
The advice I give my friends and family is to hope for the best, prepare for the worst. We are in uncharted waters.

Institute News

Should you be worried about the never-before-seen coronavirus outbreak?

AuthorSumit Chanda, PhD
Date

February 21, 2020

Here’s what Sumit Chanda, PhD, director of Sanford Burnham Prebys’ Immunity and Pathogenesis Program, has to say about the virus spreading fear around the world.

  1. What is coronavirus?
    Coronaviruses are a large family of viruses common in animals but can leap to humans, causing illnesses ranging from a common cold to severe respiratory diseases such as pneumonia, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS).
  2. What is the concern?
    Health experts are monitoring the outbreak first identified in Wuhan City (China), originating at a large seafood and animal market. It appears to be a new type of coronavirus that can be passed human-to-human, and it has caused more than 75,000 infections. New cases have been identified in 26 countries, including the United States. Thousands of people have died. 
  3. Isn’t there a vaccine for the virus?
    Since this is a new coronavirus, there is no vaccine—and developing one can take several years.
  4. Should the rest of the world be worried?
    Given the pace of global travel in today’s world, it’s a reality that the virus is only a plane ride away. International airports, including some in the U.S., are screening passengers from Wuhan City and other Asian cities where the virus has been detected. It’s important to note that SARS and MERS, also coronaviruses, kill up to 30% of the people infected, although it’s too early to know the lethality of the Wuhan coronavirus.

If you’ve traveled to the affected areas—or been in close contact with someone who has—and develop a fever accompanied by coughing, shortness of breath, and/or tightness of the chest, seek medical attention immediately, and do not travel into public spaces.

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New research explains why HIV is not cleared by the immune system

Authorsgammon
Date

April 13, 2016

Scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) and the University of North Carolina (UNC) School of Medicine have identified a human (host) protein that weakens the immune response to HIV and other viruses. The findings, published today in Cell Host & Microbe, have important implications for improving HIV antiviral therapies, creating effective viral vaccines, and advance a new approach to treat cancer. Continue reading “New research explains why HIV is not cleared by the immune system”

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Using “Big Data” to combat the flu

Authorsgammon
Date

December 9, 2015

SBP has helped lead an international team of academic and pharmaceutical scientists that have tapped into publically available large-scale ‘Omics’ databases to identify new targets to treat influenza — the virus that causes annual epidemics and occasional pandemics. The study, published in Cell Host and Microbe, reflects a breakthrough approach using advanced computational designs to identify new factors that can be targeted to prevent viruses from spreading. The research team also created a website with open access for scientists to cull additional host-targets to develop the next-generation of anti-influenza drugs. Continue reading “Using “Big Data” to combat the flu”

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Researchers reawaken sleeping HIV in patient cells to eliminate the virus

Authorsgammon
Date

September 9, 2015

Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified a new class of drugs that may be used to purge pockets of dormant HIV from a patient’s body, eliminating the virus once and for all. Fortuitously, these agents are already being explored in clinical trials for treating cancer, which could speed up the route to approval for treating HIV.

Antiretroviral therapies have made it possible for people to live with AIDS for decades. However, small reservoirs of a patient’s cells hide the virus. That is, HIV’s genes live in the cells, but its genetic code is never read to make protein, and so the virus goes undetected by the immune system.

“If you take people off the antiretroviral therapies, some of these dormant cells reawaken to make more virus,” said lead author Lars Pache, PhD, a postdoctoral fellow in the lab of Sumit Chanda, PhD, director of the Immunity and Pathogenesis Program at SBP. “The key for a cure for HIV is to purge these cells that have dormant HIV.”

Reactivating latent HIV-infected cells so that they can be killed off once and for all is called ‘shock and kill.’ The approach has remained elusive so far, because drugs that reawaken the virus could also trigger massive immune system activation, which itself could be deadly, Chanda said.

The new study, published September 9 in the journal Cell Host & Microbe, “uses a class of drug called Smac mimetics to tap into a cell pathway that can be used to wake up the virus but, based on clinical studies and our data, doesn’t appear to activate the immune system,” Chanda added.

The study started with a broad search of genes within the host cells that help keep the virus silent. Chanda’s group identified 651 genes. They then created batches of cells in which each one of those genes was silenced, and they measured how much HIV the cells produced after they were exposed to the virus.

The scientists whittled the list of candidate genes down to 139, to 24, and then 12 using increasingly stringent criteria. The absence of one gene in particular, BIRC2, boosted the activity of HIV. Even better, Smac mimetics—already proven safe in early-stage clinical trials for cancer—works by inhibiting BIRC2 and related molecules.

“These experiments led us to develop a strategy of using Smac mimetics to reawaken dormant HIV so that we could then kill it with anti-viral therapy,” said Chanda.

Chanda’s colleague at SBP, Nicholas Cosford, PhD, professor in the Cell Death and Survival Networks Program, had recently described a potent BIRC2 inhibitor, SBI-0637142. “This drug is about 10-100 times more potent than the small molecules currently in clinic development, making it a promising candidate to tackle HIV latency,” says Chanda.

Part of the reason that HIV’s genes stay hidden in its host is that they cover themselves with tightly wound DNA. A class of drugs called histone deacetylase inhibitors, which unfurls the DNA, is used to treat a variety of conditions. Although most of these inhibitors haven’t worked well on their own to reactivate latent HIV, they might work well with Smac mimetics including SBI-0637142, Chanda’s group reasoned.

The key question was whether they could reactivate the virus in cells from HIV-infected patients undergoing antiretroviral therapy. They combined SBI-0637142 with a histone deacetylase inhibitor (panobinostat) and saw signs that the virus had reawakened without triggering immune cell death.

“We anticipated that we would see a synergy because the drugs work along parallel pathways. What we didn’t expect was the level of activation—the potency and efficacy with which we were able to reverse latency in patient samples,” Chanda said.

They saw similar results in patient cells treated with a combination of LCL161—a Smac mimetic that is already in phase 1 and 2 trials for treating cancer—and panobinostat. “This is a one-two punch for HIV,” said Chanda, adding that ultimately, a cocktail of drugs will be necessary to cure HIV.

The scientists hope to partner with a pharmaceutical company to develop these molecules for testing in animal models of HIV and then move them into the clinic if they meet the safety and efficacy criteria.

In addition to SBP, the study consortium included the University of Utah School of Medicine, The Salk Institute for Biological Studies, the Perelman School of Medicine at the University of Pennsylvania, the Icahn School of Medicine at Mount Sinai, the Paul-Ehrlich-Insitut, and the German Center for Infection Research.

This post was written by Kelly Chi, a freelance science writer. 

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Research offers a new approach to improving HIV vaccines

Authorsgammon
Date

June 4, 2015

In a scientific discovery that has significant implications for preventing HIV infections, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) have identified a protein that could improve the body’s immune response to HIV vaccines and prevent transmission of the virus. Continue reading “Research offers a new approach to improving HIV vaccines”