New coronavirus approach shows promise in study, California scientists say

To try to stay ahead of any future pandemics, scientists at Scripps Research in La Jolla are taking a deeper look into the proteins that coronaviruses depend on to survive. And with their findings, they hope to develop next-generation treatments and adjust to potential mutations.

A study published in June in the scientific journal PLOS Biology uncovered 32 proteins “essential for the earliest stage of infection” of SARS-CoV-2, the coronavirus that causes COVID-19, as well as cellular pathways that are exploited and the 27 proteins the virus uses later.

When researchers pitted those same human proteins against three viruses — SARS-CoV-1, Middle East respiratory syndrome coronavirus and a seasonal coronavirus — they found that 17 of the proteins were used across the board. Two of them were identified as especially promising drug targets.

The paper includes what scientists describe as early proof of concept in mice that a certain drug class could work.

The Calibr-Skaggs Institute for Innovative Medicines, a nonprofit drug discovery division of Scripps Research, is in the early stages of harnessing the new research and developing associated therapies, according to Sumit Chanda, a professor of immunology and microbiology at Scripps Research and co-senior author of the study.

Rather than focusing on the antiviral medications that target the virus itself, the study’s approach focuses on how the virus interacts with the host.

According to Scripps Research, the team used genome-wide small interfering RNA, or siRNA, screening to find out which proteins SARS-CoV-2 relies on. Researchers were able to individually inhibit human genes in cells and thus discover which of the 20,000 genes in the human body the virus needs in order to replicate.

A microscope image of human epithelium cells, in blue, infected with SARS-CoV-2, in red, demonstrates the virus spreading from cell to cell. (Laura Martin-Sancho)
A microscope image of human epithelium cells, in blue, infected with SARS-CoV-2, in red, demonstrates the virus spreading from cell to cell. (Laura Martin-Sancho) 

Chanda said it’s important to take a precise approach to COVID-19 care and develop next-generation treatments.

“All viruses come from someplace,” Chanda said. “They’re not made out of nothing, they evolve from other coronaviruses. So if you’re hitting all existing coronaviruses, chances are you’re going to be hitting future coronaviruses.”

“The virus was sequenced very early in the pandemic, but that only gave us half the picture,” he added. “The other half of the picture is the human genes the virus uses for its replication. So now we have the other half of the picture.”

Chanda couched the significance of the study and further research in the context of changing recommendations for COVID-19 vaccinations and COVID case rates. Federal health officials decided this month not to recommend the shots as a routine step for nearly all Americans and instead leave the decision to individuals, preferably after seeking medical advice.

Data from the U.S. Centers for Disease Control and Prevention indicates that test positivity across the country jumped from 2.9% at the time the study was released to 9.5% the week of Sept. 13.

A report on respiratory viruses from the San Diego County Health and Human Services Agency said there had been 6,331 COVID cases in the county between June 29 and Sept. 6.

“COVID cases are really ticking up this year,” Chanda said. “I think between that and the new guidance on the vaccine … you’re going to see a lot more people not getting updated vaccines. So … we desperately need new drugs for COVID. … For people in high-risk groups, it’s not an inconvenience — it’s a life-or-death situation.”

“You can essentially think of it like a forest fire out in San Diego,” Chanda added. “If you can douse the embers while they’re back in a hill someplace in the back country before it turns into a major fire, that’s always a better position to be in than having to knock down a huge fire that’s threatening homes and lives.

“The best thing to do is to set up a good defensive strategy where if any of these do break through, we have the equipment in the form of antivirals, in the form of vaccines, to douse the ember before it becomes a raging forest fire.” ♦



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