EXCLUSIVE: UCSF lab says secret to killing COVID-19 variants may lie in targeting human protein

ByLuz Pena KGO logo

Wednesday, February 17, 2021

Exclusive look inside UCSF lab researching how to kill COVID-19 variants

There are multiple COVID-19 variants circulating the Bay Area, making it harder for this pandemic to be under control.

SAN FRANCISCO (KGO) -- There are multiple COVID-19 variants circulating the Bay Area, making it harder for this pandemic to be under control.

ABC7 News reporter Luz Pena got an exclusive look at a UCSF lab where scientists are studying the mutated genes of the COVID-19 variants, hoping to figure out the best drugs to kill it.

"We were the first lab in the world back about a year ago to clone each of these genes," said Dr. Nevan Krogan, director of UCSF's Department of Quantitative Biosciences Institute.

Dr. Krogan says the QBI is the epicenter of a worldwide COVID-19 collaborations involving labs across the world.

"So there is a large team of scientist's studying the SARS-CoV-2 virus. In particular, we are able to isolate different components of the virus. We can clone out each of the genes. Approximately 30 genes, one at a time, and we can study them in isolation," said Dr. Korgan

Dr. Krogan is leading the way in understanding how and why COVID-19 keeps mutating.

"The approaches we are taking is trying to find drugs that will target the human proteins that the virus needs to infect our cells," said

To expedite the COVID-19 research, they sent the genes to 450 labs in 42 countries for collaboration.

"We identified about 350 human proteins in our cells which we think the virus needs in order infect us. We looked at those proteins and cross reference it to libraries of drugs that are out there and then say which drugs target these proteins," said Dr. Krogan.

According to Dr. Krogan, there are 26 drugs being tested in clinical trials for COVID-19.

"The cancer drug called Aplidin targets a human protein called EIF1-A. This is a protein involved in making other proteins in our cells and the virus hijacks it to make its own proteins," said Dr. Krogan.

He believes the most effective drugs will need to target the human protein.

"We don't have to worry about our proteins mutating or getting resistance to that drug, because we don't mutate as fast as the virus. Secondly, the virus in my opinion will never mutate enough to get around reliance on that human protein. So, if we can get drugs that will target the human protein the virus needs, it's not going to matter how much the virus mutates, we are still going to get it," said Krogan.

Luz Pena: "When you are targeting the human protein, can that also have a negative impact?"

Dr. Krogan: "Yes, there are definitely side effects targeting human proteins and it may be counter intuitive to target a human protein when you have these viral proteins you can be targeting. However, a couple key points is that most drugs we use for diseases are targeting the human protein."

To understand which drugs will work best, they are studying each variant.

While pointing to a computational modeling of the South African variant, Kliment Verba, a Quantitate Bioscience Institute fellow, explained, "In red are the South African mutation. You can see there is a number of mutations right where this potential therapeutic could bind and this means that this therapeutic might not work well with that variant."

Dr. Krogan believes we have the answers within our bodies.

"It's the same genes being mutated in cancer that are being hijacked by SARS-CoV-2. It's the same genes being mutated in Parkinsons that are being hijacked by Zika. For me, it's not a surprise you have these Achilles heels in the cells that become mutated and result in disease X Y and Z or the virus, which is very smart evolves to attack these key notes," said Dr. Krogan.

Lorena Zuliani-Alvarez, the science project manager for the QBI Coronavirus Research Consortium, says they've noticed a pattern with the variants.

"The virus is mutating the same proteins, for example NSB3 and NSB6, as you can find here. Our strategy is to target host protein, instead of viral proteins because that will not mutate and we have shown that certain drugs can target all these variants equality," said Zuliani-Alvarez.

Dr. Krogan hopes the global collaboration we are seeing now with COVID-19 research becomes the model for other diseases.

"The challenge is to try to keep the spirit of collaboration in place. This infrastructure in place so that we are better prepared for the next pandemic, because we know it's coming. The larger question is why we are not working on all diseases like this like breast cancers, and Alzheimer's and Parkinson's? I believe if we do we would get treatments a lot quicker," said Krogan.

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