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Finding New Ways to Fight Coronavirus … From Studying Bats

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David Veesler/Credit: University of Washington Medicine, Seattle
 

David Veesler has spent nearly 20 years imaging in near-atomic detail the parts of various viruses, including coronaviruses, that enable them to infect Homo sapiens. In fact, his lab at the University of Washington, Seattle, was the first to elucidate the 3D architecture of the now infamous spike protein, which coronaviruses use to gain entry into human cells [1]. He uses these fundamental insights to guide the design of vaccines and therapeutics, including promising monoclonal antibodies.

Now, Veesler and his lab are turning to another mammal in their search for new leads for the next generation of antiviral treatments, including ones aimed at the coronavirus that causes COVID-19, SARS-CoV-2. With support from a 2020 NIH Director’s Pioneer Award, Veesler will study members of the order Chiroptera. Or, more colloquially, bats.

Why bats? Veesler says bats are remarkable creatures. They are the only mammals capable of sustained flight. They rarely get cancer and live unusually long lives for such small creatures. More importantly for Veesler’s research, bats host a wide range of viruses—more than any other mammal species. Despite carrying all of these viruses, bats rarely show symptoms of being sick. Yet they are the source for many of the viruses that have spilled over into humans with devastating effect, including rabies, Ebola virus, Nipah and Hendra viruses, severe acute respiratory syndrome coronavirus (SARS-CoV), and, likely, SARS-CoV-2.

Beyond what is already known about bats’ intriguing qualities, Veesler says humans still have much to discover about these flying mammals, including how their immune systems cope with such an onslaught of viral invaders. For example, it turns out that a bat’s learned, or adaptive, immune system is, for the most part, uncharted territory. As such, it offers an untapped source of potentially promising viral inhibitors just waiting to be unearthed, fully characterized, and then used to guide the development of new kinds of anti-viral therapeutics.

In his studies, Veesler will work with collaborators studying bats around the world to characterize their antibody production. He wants to learn how these antibodies contribute to bats’ impressive ability to tolerate viruses and other pathogens. What is it about the structure of bat antibodies that make them different from human antibodies? And, how can those structural differences serve as blueprints for promising new treatments to combat many potentially deadly viruses?

Interestingly, Veesler’s original grant proposal makes no mention of SARS-CoV-2 or COVID-19. That’s because he submitted it just months before the first reports of the novel coronavirus in Wuhan, China. But Veesler doesn’t consider himself a visionary by expanding his research to bats. He and others had been working on closely related coronaviruses for years, inspired by earlier outbreaks, including SARS in 2002 and Middle East respiratory syndrome (MERS) in 2012 (although MERS apparently came from camels). The researcher didn’t see SARS-CoV-2 coming, but he recognized the potential for some kind of novel coronavirus outbreak in the future.

These days, the Veesler lab has been hard at work to understand SARS-CoV-2 and the human immune response to the virus. His team showed that SARS-CoV-2 uses the human receptor ACE2 to gain entry into our cells [2]. He’s also a member of the international research team that identified a human antibody, called S309, from a person who’d been infected with SARS in 2003. This antibody is showing promise for treating COVID-19 [3], now in a phase 3 clinical trial in the United States.

In another recent study, reported as a pre-print in bioRxiv, Veesler’s team mapped dozens of distinct human antibodies capable of neutralizing SARS-CoV-2 by their ability to hit viral targets outside of the well-known spike protein [4]. Such discoveries may form the basis for new and promising combinations of antibodies to treat COVID-19 that won’t be disabled by concerning new variations in the SARS-CoV-2 spike protein. Perhaps, in the future, such therapeutic cocktails may include modified bat-inspired antibodies too.

References:

[1] Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer. Walls AC, Tortorici MA, Bosch BJ, Frenz B, Rottier PJM, DiMaio F, Rey FA, Veesler D. Nature. 2016 Mar 3;531(7592):114-117.

[2] Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Cell. 2020 Apr 16;181(2):281-292.e6.

[3] Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Pinto D, Park YJ, Beltramello M, Veesler D, Cortil D, et al. Nature.18 May 2020 [Epub ahead of print]

[4] N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. McCallum M, Marco A, Lempp F, Tortorici MA, Pinto D, Walls AC, Whelan SPJ, Virgin HW, Corti D, Pizzuto MS, Veesler D, et al. bioRxiv. 2021 Jan 14.

Links:

COVID-19 Research (NIH)

Veesler Lab (University of Washington, Seattle)

Veesler Project Information (NIH RePORTER)

NIH Director’s Pioneer Award Program (Common Fund)

NIH Support: Common Fund; National Institute of Allergy and Infectious Diseases

7 Comments

  • Kristine A Anderson says:

    I got Histoplasmosis in 1982 from breathing in spores from nearby bat poop (unknown to me of course). Then I got RA and ME/CFS from Histo. Now some Covid Long-Haulers are getting ME/CFS. Is there a possible relationship between bats, Covid and ME/CFS?

    • Christi says:

      I have a similar question. I have had histoplasmosis & was wondering if my body produced antibodies for histoplasmosis …
      and if histoplasmosis antibodies could help in fighting off covid, since both diseases are bat related. I can’t find much info about that. This article is the most I could locate so far.

  • Mark Headley says:

    Batman? Superman? How do we know the difference is Bat antibodies? Batman? Superman? How do we know the difference is Bat antibodies? What about other aspects of bat immune systems v. ours? What about receptors for viruses?

  • John Hasty BS MT(ASCP) Retired says:

    Bats are not that important, what we should be studying is the effects of the spike protein on the human body’s complement system.

  • MRKRUSS@AOL.COM says:

    When we think about Leonardo Da Vinci, 99% of all people say—-“The Mona Lisa”. Most people in Medicine don’t realize that the first Renderings of the Internal Human Body was done by Michelangelo and Da Vinci in the early 1500’s. Most don’t realize that Da Vinci was one of the first in Air Flight—-The Bat Wing Glider and the Small Bat Wing Model Airplane. “In 1904 Orville and Wilber Wright had the First Fixed Air Flight” and most don’t realize that (14) years prior Clement Adder in France had the first Winged Air Flight powered by a 122 lb. Steam Engine and Wings Modeled after Bat Wings (Da Vinci Designs).

    In the early 1900’s we Developed Sonar based upon Bat’s Echo Location. We have also Developed Echo Location for Blind People to Navigate based upon Bat’s Echo Location. What if we use Music Notation to add to Echo Location like—-Bass, Alto, Tenor, Song, Rhythm, Cadence, and Beat. My idea is to use 100’s of Sounds and Rhythms to help in the Navigation for the Blind. We should be able to use 100’s of Rhythms, Sounds, and Meter Cadences at the same time. A Truck might be a Base Sound and a Street Light might be a Shuffle Rhythm Sound. People to the right might be a Soft Harmony Sound like a Alto Song along with a Brisk Musical Beat. When you hear a Concert you might hear 100’s of sounds at the same time and you can make sense of those sounds.

    A Bats Hearts go up to 1,000 beats per minute while in Flight and their Immune Systems are Incredible. (3) Species of Vampire Bats can their Blood as a Blood Thinner. We have also developed Echo Cardiogram’s based upon Bat’s. I wonder what we can learn.

    “WHAT IF”

  • R. Araujo says:

    Dr. Collins, thank you so much for your blog! Such condensed and rich nuggets of weekly intellectual nourishment. I look forward to them week after week.
    Thank you for sharing the inspiration on top of all you do for the NIH!

  • West says:

    I believe our immune system is strong enough to fight the coronavirus . . .

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