Some thoughts on SARS-CoV-2 and heparan sulfate

After an interaction on Twitter with a colleague who is associated with #LongCovid and #TeamClots, he asked me for some references. I thought what to send, and then realised that references plus something a bit more than a Tweet might be useful, so here goes.

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Clots and vaccines

Blood clots, for example, deep vein thromboses or pulmonary embolisms, are serious and we should rightly be concerned about these. With ~ 17 M doses of the AZ vaccine delivered into people, we have reports of 15 cases of deep vein thrombosis and 22 cases of pulmonary embolism. Deep vein thrombosis occurs at rate of 0.1% (so 1 in 1000) across all age groups, increasing with age. So every day that means around 47 cases in a population of 17 million – in fact it will be more, because those vaccinated are not representative of the population, but an older segment.

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Where are the plans?

In three weeks schools re-open and a few weeks later undergraduates return to university. Universities appear to be moving to a model of having all students in attendance, and using a lot of remote teaching. This in itself is not necessarily a bad idea, as there will be facilities available and for 1^st years in Halls and for many later year undergraduates they may have better internet connectivity, plus there is the library various computer rooms.

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Heparin inhibits SARS-cov-2 cell infectivity

With new data in hand, our first preprint on SARS-cov-2 receptor binding domain (RBD) interacting with heparin now has a sibling, which demonstrates that heparin inhibits the infection of Vero cells by SARS-cov-2

Some of the key points of the team’s new work are:

1. Inhibition of viral infectivity in a Vero cell model by heparin, which is a better inhibitor for SARS-cov-2 than SARS-cov.
2. Analysis of the interactions of a more extended library of model heparins with the SARS-cov-2 receptor binding domain. As with many other heparin-binding proteins, these data show that while sulfation is critical for RBD binding, the amount of sulfate is not, but instead it is the spatial arrangement of sulfate groups that is most important.

Together the data point to heparin being a potentially useful therapeutic to reduce infectivity.

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The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding

Thursday last week (Feb 27) Mark was up from Keele and popped his head around my office door – not a surprise, as he is often here to do circular dichroism on various heparin-binding proteins – to announce that Marcelo had managed to make some SARS-CoV-2 S1 receptor binding domain. Mark had asked Hao,  my postdoc, to do some SPR measurements to see if it bound heparin.

Later in the day I went over to the SPR/CD lab to find Courtney, Mark’s PhD student and Mark beavering away on the CD. A quick discussion. Hao had finished some work on our first grade A heparin functionalised SPR surface, so we set about injecting the SARS-CoV-2 surface protein (Spike) S1 Receptor Binding Domain – a one shot experiment, as amounts of protein were limited, so we injected 1 mL at 500 µL/min (I like high flow rates as mixing is way better, though still far from perfect).

Bingo.

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