Paul Has Measles is a children's book about viruses and vaccines available in English (download pdf) Spanish (download pdf) French (download pdf) German (download link) Portuguese (download pdf) Romanian (download pdf), Italian (download pdf), Croatian (download pdf) Mixtec (download pdf) Hindi (download pdf) Russian (download pdf) Japanese (download pdf) Nahuatl (download pdf) Arabic (download pdf) Chinese (download pdf) and Mayan (download pdf). Kindle and paperback versions also available at Amazon in English, Spanish, French.

Virus batteries

Virus Batteryby Gertrud U. Rey

Lithium-ion batteries produce power when lithium ions flow from a negative electrode to a positive electrode through an electrolyte medium. The positive electrode is usually composed of a lithium compound and the negative electrode is typically graphite (crystalline carbon).

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By David Tuller, DrPH

And here’s yet another study from Professor Trudie Chalder and colleagues at King’s College London, this time tackling fatigue in people with HIV—an often debilitating problem. The study—“A Biopsychosocial Approach to HIV Fatigue: A Cross-Sectional and Prospective Analysis to Identify Key Modifiable Factors”—was published online last month by the journal Behavioral Medicine.

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SARS-CoV-2: Could it be bad?

coronavirusHealth experts say it’s not a question of whether SARS-CoV-2 will spread within the U.S., but when. A CDC official said yesterday, “We are asking the American public to prepare for the expectation that this might be bad.” What exactly does that mean?

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By David Tuller, DrPH

Leonard Jason, a professor of psychology at DePaul University in Chicago, is a recognized expert in research on the prevalence of and case definitions for the illness (or cluster of illnesses) variously referred to as myalgic encephalomyelitis, chronic fatigue syndrome, ME/CFS, CFS/ME and other names. I posted an interview with him on case definition a couple of years ago.

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By David Tuller, DrPH

I have been trying to find out why Mahana Therapeutics, a San Francisco-based start-up, has chosen to disseminate misleading information about a web-based cognitive behavior therapy program for people with irritable bowel syndrome. Because Mahana’s co-founder and CEO, Rob Paull, has not responded to my letters, I have contacted some of those listed as science advisors on the company’s website.

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The TWiV team returns this week to SARS-CoV-2019 coverage to review the latest epi curves, the fatality rate, furin cleavage site and receptor binding domain in the spike glycoprotein, related CoV recovered from pangolins, evidence that the virus did not escape from a laboratory, and many more questions sent in by listeners.

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Show notes at microbe.tv/twiv

coronavirus SpikeA coronavirus related to SARS-CoV-2 has been isolated from Malayan pangolins illegally imported into Guangdong province. It is not the precursor of SARS-CoV-2, but comparison of viral genome sequences provides further evidence that the virus currently infecting humans was not produced in a laboratory.

There are two important sequences in the viral spike glycoprotein (pictured) that are important for tracing the origin of SARS-CoV-2: a furin cleavage site (discussed last week) and the receptor binding domain (RBD).

The results of experiments in cells in culture have shown that the SARS-CoV-2 spike glycoprotein binds the cell receptor ACE2. Six amino acids in the RBD are critical for binding to this receptor. Five of these six amino acids differ in the RBD of SARS-CoV-2 compared with sequence from the bat virus RaTG13, the most closely related virus. The SARS-CoV-2 spike glycoprotein binds ACE2 with high affinity, an outcome not predicted by computational analysis of the RBD sequence. If someone were to engineer an RBD into a bat SARS-like CoV to allow efficient infection of human cells, they would not use the amino acid sequence in the SARS-CoV-2 spike. Rather the specific sequence was likely selected during replication in cells with human-like ACE2.

As discussed previously, the furin cleavage site in the SARS-CoV-2 spike is not present in the bat virus RaTG13. Its acquisition could allow enhanced infection of human cells. In addition to the furin cleavage site, an extra proline is also present, a change predicted to lead to the addition of O-linked glycans in the vicinity. If someone were to engineer the furin cleavage site into the spike, it is not likely that the extra proline would have been included. Furthermore, the addition of such glycans typically occurs under immune selection.

The genome sequences of CoVs recently isolated from pangolins are not close enough to SARS-CoV-2 to have been its immediate progenitor. However, the RBD of these pangolin CoVs are identical to that of SARS-CoV-2 at 6 of 6 of the key amino acids discussed above. This observation indicates that passage of CoV in a host with human-like ACE2 could select for a RBD with high-affinity binding. Such passage could also select for insertion of the furin cleavage site, which is not present in pangolin CoVs. Once a virus with the appropriate RBD and furin cleavage site arose in an animal – a bat or intermediate host – it would then replicate once introduced into humans.

Another possibility is that viruses with the correct RBD have been repeatedly jumping into humans, but efficient human to human transmission was not established until the acquisition of the furin cleavage site. Such is the scenario with MERS-CoV, which has jumped multiple times from camels to humans, but each chain of infection is short and soon ends. The virus has never become established in humans because the required mutations have not entered the viral genome. Serological surveys specific for SARS-CoV-2 might test this hypothesis for its emergence.

Could laboratory passage of a bat SARS-like virus lead to isolation and accidental emergence of SARS-CoV-2? This scenario would require starting with a virus that is very close to the current isolates. Passage in cell culture might have selected for the RBD amino acid changes to enable high affinity ACE2 binding. However this virus would have had to be very similar to SARS-CoV-2, and no such isolate is known to be present in any laboratory. Selection of viruses with a furin cleavage site would likely have taken extensive passaging in cells. Finally, it is unlikely that the O-linked glycan addition site would have emerged without immune pressure, which is absent in cell cultures.

Proving or disproving any of these hypotheses for the emergence of SARS-CoV-2 might never be possible. Nevertheless, isolation of SARS-like viruses from a variety of animals might help to clarify the steps to emergence in humans. For MERS-CoV, a priority should be to prevent human infections, perhaps by immunizing camels, to avoid the emergence of another epidemic CoV with sustained transmission in humans.

By David Tuller, DrPH

When I was in Australia two years ago–wow, can’t believe it’s been that long!–I spent some time with Dr Mark Guthridge, an associate professor of biomedical science at Deakin University in Melbourne. Several years ago, after a bout of mononucleosis/glandular fever, he developed myalgic encephalomyelitis, which in Australia even patients and specialist doctors generally call chronic fatigue syndrome. (Actually, many or most actually say “chronic fatigue”–I kept trying to nudge people to at least use the word “syndrome,” but it was a pretty hopeless endeavor.)

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By David Tuller, DrPH

Last week, I wrote to Rob Paull, the co-founder and CEO of Mahana Therapeutics, regarding the company’s misleading claims about the web-based cognitive behavior therapy program for irritable bowel syndrome it recently licensed from King’s College London. I have also written to Professor Rona Moss-Morris, the co-lead investigator of ACTIB, the study that road-tested the program, as well as three of Mahana’s prominent gastroenterology advisors.

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coronavirus SpikeThe spike glycoprotein of the newly emerged SARS-CoV-2 contains a potential cleavage site for furin proteases. This observation has implications for the zoonotic origin of the virus and its epidemic spread in China.

The membrane of coronaviruses harbors a trimeric transmembrane spike (S) glycoprotein (pictured) which is essential for entry of virus particles into the cell. The S protein contains two functional domains: a receptor binding domain, and a second domain which contains sequences that mediate fusion of the viral and cell membranes. The S glycoprotein must be cleaved by cell proteases to enable exposure of the fusion sequences and hence is needed for cell entry.

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