One Cat Out of Millions is Not a Trend: A Science-Based Look at the Unlikely Risk of COVID-19 Infection in Cats

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Guest post by Ingrid R. Niesman, MS PhD

Like many of you, my two Siamese buddies have been keeping me company and keeping me amused while I struggle to figure out how to convert my lab-based life to an online life. With a recent report coming out of Belgium that an owner’s cat not only tested positive, but actually got sick with COVID-19, I am worried about our pets . Yet, as a biologist, I realize that one out of millions is most likely an anomaly, not a trend. There is probably an explanation, and the answer lies buried in molecular science.

We have an ACE2 in the hole

I analyzed the genetic sequence of human verses feline ACE2 last month. ACE2 is the primary receptor identified in humans to which the COVID-19 virus, SARS-CoV-2, finds and latches onto in the nasal and oral cavities. In my previous post, I did find that key amino acids needed for the virus and the ACE2 protein to interact were identical between human, dogs and cats. Others have also pointed this out. A February 17th publication suggests that multiple different kinds of animals, from reptiles to mammals, have very similar sequences to human ACE2, thus making it possible, from a genetic perspective, that they could be infected by SARS-CoV-2.

Infected and infectious are two different concepts 

Just because it’s possible that SARS-CoV-2 potentially interacts with feline ACE2 doesn’t mean that it can, or that the interaction is strong enough to elicit invasion of the virus into a cell, or that enough cells are invaded to cause disease. If feline ACE2 is somehow fundamentally different on a molecular level than that of humans, then few cells are infected in the first place. Any viruses that might be released will have nowhere else to go, and normal feline immune responses will mop up the damage. No viral propagation, no viral shedding, and therefore, no pet to human transmission.

Science is outracing this disease

Between scrolling through the frightening daily news and fighting my cats for my keyboard, it’s hard to keep up with the breakneck speed of scientific discovery about COVID-19. I follow work that describes how the virus attaches to and invades cells, along with research using cryo-electron microscopy to visualize protein structure.

Last week in Science, another structural biology study was published where they analyzed the binding of SARS-CoV-2 to a realistic natural configuration of human ACE2. They found that certain sugar modifications of ACE2 and one specific building block of ACE2, the amino acid methionine #82, are critical for viral attachment to a cell.

Briefly, all proteins are built in a linear assembly line manner. To acquire function, each protein must be folded into unique origami-like shapes. This is partially accomplished by adding sugar modifications to the amino acid building blocks. When I compared the known human modified sites to feline modified sites, I found four major differences. This is good news.

Small changes create big differences when you are at molecular levels

As SDSU Biochemistry Professor Dr. Tom Huxford explains, “sugars decorate the outsides of proteins on the surfaces of cells, and a lot of times those sugars provide sticky points of attachment for passing immune cells or viruses alike.” Therefore, if the needed sugar residues for the COVID-19 attachment are not as easily accessible on the feline ACE2, much less virus can bind.  “Slight changes in the protein’s surface can drastically affect the placement of surface sugars and interfere with the virus’ ability to stick to the cell and eventually enter it,” adds Dr. Huxford.

Besides these sugar clumps, I found another major change that can profoundly affect how this virus interacts with and stays connected to ACE2. Entry into a cell isn’t instantaneous. “A virus relies on a good ‘fit’ with proteins on the surface of a cell,” says Dr. Huxford. “Sometimes that fit involves electrical attraction between oppositely charged groups. If a virus is relying on this type of interaction and it finds a different charge on the surface, then it will fall off the cell and fail to infect.”

More good news for cat lovers

Methionine #82 of human ACE2 is shown to strongly hold onto an amino acid of the spike protein of SARS-CoV-2 using these types of electrostatic charges. In cats, this pivotal amino acid is substituted for one without a charge, most likely weakening this strong interaction and reducing the likelihood that a cell can be invaded.

We will need significant basic biology to see if these differences are the basis for fewer infections and disease in cats over human hosts.

At this stage of the current crisis, as of Tuesday, more than 800,000 people worldwide have been infected by the virus. We only know of the one cat in Belgium that we think was infected.

Numbers don’t lie. I wish I had the same odds.

Ingrid R. Niesman MS PhD is the Director of the SDSU Electron Microscope Imaging Facility at San Diego State University. She graduated from Utah State University and received her MS from the University of Illinois-Urbana-Champaign. After 30 years of technical electron microscopy, cell biology, neuroscience and infectious disease research, Dr. Niesman completed her PhD in the UK at the University of Sunderland. Her work experience includes time at LSU Medical School, Washington University, UAMS in Little Rock, UCSD, TSRI and a postdoctoral year at CALIBR in La Jolla, CA. She has worked for at least two National Academy of Science members and is credited with over 50 publications. She can be reached at ingridniesman@yahoo.com

References:

Structure analysis of the receptor binding of 2019-nCoV Yun Chen, Yao Guo, Yihang Pan, Zhizhunag Zhao, Biochemical and Biophysical Research Communications Vol. 525, Issue 1, pp. 135-140 https://doi.org/10.1016/j.bbrc.2020.02.071

Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 Renhong Yan1,2, Yuanyuan Zhang1,2,*, Yaning Li3,*, Lu Xia1,2,Yingying Guo1,2, Qiang Zhou1,2,Science  27 Mar 2020: Vol. 367, Issue 6485, pp. 1444-1448 DOI: 10.1126/science.abb2762

8 Comments on One Cat Out of Millions is Not a Trend: A Science-Based Look at the Unlikely Risk of COVID-19 Infection in Cats

  1. Kelley
    April 5, 2020 at 7:14 pm (2 months ago)

    Ingrid, I’m very worried about this. Very worried. As a cat rescuer, I know cats have enough problems without panicked owners turning their cats in to shelters or even dumping them out of fear. And it’s a tiger. That being a tiger shouldn’t ever be within 6 feet of humans unless it’s been tranquilized for some medical procedure and then the people working with it should be masked and gloved. https://www.axios.com/tiger-coronavirus-bronx-zoo-4582f9db-9c71-45b5-a7b8-df9886b4256e.html?utm_source=facebook&utm_medium=social&utm_campaign=organic&utm_content=1100

    Reply
    • Ingrid
      April 6, 2020 at 5:33 am (2 months ago)

      It has me concerned, too, Kelley. Keep in mind that there’s probably still a lot more that we don’t know about how the novel coronavirus interacts with other species than what we do know. I have a lot of questions about what is happening with these tigers. For starters, did they only test for COVID-19? There are other viruses/bacteria that could cause the symptoms the tigers showed. Would the test medium they used also test positive for other coronaviruses? I still think, with everything we do know right now, the odds of our cats getting infected are extremely low. I’ll provide more information if/as I can.

      Reply
  2. Kathryn
    April 3, 2020 at 12:50 pm (2 months ago)

    That’s great information. Thank you for posting it!

    Reply
  3. Sarah Chauncey
    April 1, 2020 at 3:06 pm (2 months ago)

    I really appreciate this clear explanation of the biological differences that make humans more susceptible to this particular coronavirus. It makes so much sense. Thank you, Dr. Niesman and Ingrid!

    Reply
  4. Timmy Tomcat
    April 1, 2020 at 1:56 pm (2 months ago)

    We really appreciate the clearing up of the sensationalist clap-trap that masquerades as news these days. Well done

    Reply
  5. Louise
    April 1, 2020 at 10:32 am (2 months ago)

    Thank you for this important article. I’d read about the one cat in Brazil. Although I didn’t think it meant all cats were susceptible I worried some people might begin to panic and
    an open season on feral or outdoor cats could begin.

    Reply
  6. Dina
    April 1, 2020 at 8:58 am (2 months ago)

    Great post. Thank you.

    Reply
  7. Janine
    April 1, 2020 at 7:37 am (2 months ago)

    I have to admit when I heard a cat did have coronavirus, I got a bit concerned. Thank you for this post calming some of my thoughts.

    Reply

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