20200418S Day 109: Review of Recent COVID-19 Related Research

Santa Cruz, CA: Today has been a slow day, like all days under shelter-in-place seem to be. I walked to the farmer’s market and the grocery store. Both places had a much larger number of people wearing masks – about 60%. Social distancing was enforced through one-way aisles and tape markers on the ground.

It is still very difficult for me to be productive. Twitter is my main time suck at the moment. There is so much posting of what appears to me as misinformation. I think it’s time to educate myself and at least see what people are saying who have taken the time to write up and submit research papers.

The first paper I’d like to review is Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates. The authors of this paper are trying to determine the structural similarity of ACE2, specifically the part of ACE2 involved in binding to SARS-CoV-2, across mammals and vertebrates. The first thing I notice is that the authors are from a diverse group of worldwide top-notch universities and organizations. Some points of interest to me are:

  1. There are 25 amino acids at the ACE2 binding site which are important for binding to SARA-CoV-2.
  2. Molecular phylogenetics shows that at least one human coronavirus (HCov-OC43) may have originated in cattle or swine. HCov-OC43 is a beta coronavirus that is now believed to have been the cause of an influenza pandemic in 1889-90.
  3. 18 out of 19 catarrhine primates analyzed scored “very high” and also had 25/25 identical binding residues for binding; and the 19th, the Angola colobus, scored “high” with at least 20/25 identical binding residues.
  4. 3/3 species of Cervid deer and 12/14 cetacean species also scored “high”.
  5. Camels and pigs both scored “low”.
  6. 9/9 species of Felids scored “medium” – there have been reports that a domestic cat became infected with SARS-CoV-2.
  7. 3/3 species of pangolins scored “low” or “very low” for ACE2 binding.
  8. The ACE2 RBD residues critical for effective binding to SARS-CoV-2 S protein are S19, Q24, T27, F28, D30, K31, H34, E35, E37, D38, Y41, Q42, L45, L79, M82, Y83, N330, K353, G354, D355, R357, and R393. The ACE2 RBD glycosylation sites N53, N90 and N322 were also included.
  9. “Very High” scores have at least 23/25 matching residues, and 7/7 of the residues K353, K31, E35, M82, N53, N90 and N322, and do not have N79, and the up to 2 non-matching residues have conservative substitutions.
  10. “High” scores have at least 20/25 matching residues, have K353, have only conservative substitutions at K31 and E35, do not have N79, and up to one non-conservative substitutions among the up to 5 non-identical residues.
  11. “Medium” scores have at least 20/25 matching residues, only conservative substitutions at K353, K31, and E35, and up to two non-conservative substitutions in the 5 non-identical residues.

The second paper I noticed was Comparative dynamic aerosol efficiencies of three emergent coronaviruses and the unusual persistence of SARS-CoV-2 in aerosol suspensions. The title says it all – the researches found that SARS-CoV-2 “generally maintains infectivity when airborne over short distances, in contrast to either comparator betacoronavirus”.

A third paper, Regulation of angiotensin converting enzyme 2 (ACE2) in obesity: implications for COVID-19, found increased expression of lung ACE2 in obese mice.

A fourth paper, Transcriptional Difference between SARS-COV-2 and other Human Coronaviruses Revealed by Sub-genomic RNA Profiling, found that “SARS-COV-2 has significantly elevated expression of the Spike gene, which may contribute to its high transmissibility.”

In a fifth paper, COVID-19 pandemic: A Hill type mathematical model predicts the US death number and the reopening date, the author predicts that “by the mid June or early July 2020, the outbreak will strongly decay and the US will have about 800K confirmed cases and less than 50K deaths.”

In a sixth paper, Delayed clearance of SARS-CoV-2 in male compared to female patients: High ACE2 expression in testes suggests possible existence of gender-specific viral reservoirs, the authors find that males have delayed viral clearance after infection (by 2 days) and that the testes was one of the highest tissue sites of ACE2 expression.

And finally, a seventh paper which seems like a good one to stop with for now: Revealing variants in SARS-CoV-2 interaction domain of ACE2 and loss of function intolerance through analysis of >200,000 exomes. This one has a lay summary which sounds significantly enough to me on first reading to quote in entirety here:

Lay summary: Our researchers took a look at a sequence of DNA known as the ACE2 gene. This gene is most well known for its role in regulating blood pressure. But in recent times, it’s drawn a lot of attention from the scientific community because it may also serve as a doorway of sorts, enabling viruses like SARS-CoV-2 to infect cells. Our researchers looked at the ACE2 gene in more than 200,000 people, comparing their exact DNA sequences to see where there are differences among people. Variation in the DNA sequence of a gene is common and is sometimes meaningless. But other times, small changes in the DNA sequence can alter the protein that is made from that gene. In this case the ACE2 gene makes the ACE2 protein, which is what the SARS-CoV-2 virus interacts with. We found a lot of variation between individuals and checked to see if that variation coincided with any traits (i.e., people with variant X tend to have high blood pressure more often than people without variant X). All of the traits we looked at were non-COVID-19-related traits, meaning we haven’t asked these people anything about COVID-19 yet (this is because these DNA sequences were collected before the pandemic). We found that there are a number of variations observed among people in a specific part of the ACE2 gene. These variations are expected to alter the shape or functionality of a specific part of the ACE2 protein: The part that interacts with the SARS-CoV-2 virus. We don’t yet know what the real-life significance of this variation is, but it’s possible that these variants decrease the protein’s ability to interact with the SARS-CoV-2 virus, thus decreasing the person’s likelihood of being infected. We can speculate that there will be a spectrum of vulnerability to COVID-19 among people, where some people are more vulnerable than others, and that variants in this part of the ACE2 gene may be one of the reasons. The research we presented here shines a light on this part of the ACE2 gene and may give future researchers a direction to go in as they try to figure out what makes people vulnerable to COVID-19 and similar viruses.

Some key points mentioned in this paper:

  1. ACE2 is on the X chromosome and because males have only one X chromosome, males carry only one copy of the ACE2 gene.
  2. 332 coding variants were found that affected the ACE2 coding sequence. 16 of these were loss of function mutations. 11 coding variants changed specific amino acids that interact with SARS-CoV-2. 29 coding variants were nearby, within two amino acids.
  3. Two of the most found alleles are chrX:15600835:T:C / p.K26R (allele frequency 0.5%), chrX:15600857:A:G / p.S19P (very rare except in African ancestry with allele freq of 0.1-0.2%)
  4. A few more residues of interest that I saw were G352V, D355N, A396T, N397D, F400L, T27A, E35K, E37K, L39P, F40L, S43N, A80G, M82I, P84A, and L27F (male only).

 

Author: J. Sands Loch

Student and teacher of reality in all its forms. I self-published my personal experience of discovering and trying to understand and use a model of reality based on the Many Worlds Interpretation of Quantum Mechanics: Surfing the Multiverse: Finding Happiness One Universe at a Time Available on Kindle and from Amazon, and found in blog post form at: SurfingTheUniverse.com

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