Tag Archives: COVID-19

Happy 10th Birthday, Blopig!

OPIG recently celebrated its 20th year; and on 10 January 2023 I gave a talk just a day before the 10th anniversary of BLOPIG’s first blog post. It’s worth reflecting on what’s stayed the same and what’s changed since then.

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The SARS-CoV-2 protein spike glycosylation not only shields but primes binding by providing structural stability too

Yep, it is very well known that the sugar coating (aka glycosylation) of viruses makes them invisible to the immune system, a strategy so effective that like in the case of HIV, whose spike is almost entirely covered by glycans, makes it so difficult to target by the human immune system.

Unsurprisingly, coronaviruses such as SARS, MERS, and SARS-CoV-1(2) not only benefit from this evolutionary strategy but there is evidence now that sugars provide stability to their spikes to be effective binders by glueing the spike chains, hence making them infectious.

This is the major finding of this paper that introduces very interesting results from all-atom MD simulations of a fully glycosylated model of the  SARS-CoV-2 spike protein embedded in a realistic viral membrane. Researchers aimed to look into the stability of the protein spike (A, B, and C) chains in the “open” and “closed” conformation and how these changed upon key residue mutations to test how glycans sitting in the inter-chain space affect stability. It also aimed at quantifying glycans’ shielding effect from molecules ranging from 2 to 15 Angstroms, i.e., from small-sized to peptide- and antibody-sized molecules.  

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Antibody Engineering and Therapeutics Conference

I was invited to speak at the Antibody Engineering and Therapeutics Conference (presenting mine and Matt’s recently published epitope profiling paper), in San Diego (December 12th – 16th). Unfortunately, the pandemic had other ideas so I decided not to travel but luckily the conference was hybrid. 

The conference included 1 day of pre-conference workshops and 4 days of presentations from academic and industry, with livestreaming of the initial keynotes (including one from Charlotte). Remaining talks were recorded and made available after the conference. I’ve highlighted a few of my favourite talks and conference themes, with links to papers where available.

Naturally, a lot of the presented research related to covid-19. I was speaking in the ‘Antibody Repertoires and Covid-19’ session, where there were interesting presentations from Professor Eline Luning Prak from the University of Pennsylvania and Elaine Chen from Vanderbilt University analysing antibody responses in covid-recovered individuals, and comparing vaccine responses in covid-recovered vs covid-naiive individuals. Other talks around SARS-CoV-2 vaccines included Dr Laura Walker from Adimab/Adagio Therapeutics comparing BCR repertoire responses to different types of vaccinations, and the effect of using different booster types.

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One of my other hats – Covid-19 Response Director for UK research and innovation

The group asked me if I would tell them a little bit about one of my other hats at our regular Tuesday meeting, and this blog is about that.

In October 2019 I was seconded part-time to UKRI as the Deputy Executive Chair of the Engineering and Physical Sciences Research council (EPSRC). What is UKRI (UK research and Innovation)? It’s a non-departmental public body that funds research and innovation. It is made up of the seven disciplinary research councils (acronyms to please Tom – AHRC, BBSRC, EPSRC, ESRC, NERC, STFC and MRC), Research England, and the UK’s innovation agency, Innovate UK.

As Deputy Executive Chair of EPSRC I was helping with UKRI strategy, learning how a spending review round works, visiting universities to talk about how they could work better with UKRI – pretty much everything I was expecting to be doing. But like everyone, my world changed in early 2020.

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The Coronavirus Antibody Database: 10 months on, 10x the data!

Back in May 2020, we released the Coronavirus Antibody Database (‘CoV-AbDab’) to capture molecular information on existing coronavirus-binding antibodies, and to track what we anticipated would be a boon of data on antibodies able to bind SARS-CoV-2. At the time, we had found around 300 relevant antibody sequences and a handful of solved crystal structures, most of which were characterised shortly after the SARS-CoV epidemic of 2003. We had no idea just how many SARS-CoV-2 binding antibody sequences would come to be released into the public domain…

10 months later (2nd March 2021), we now have tracked 2,673 coronavirus-binding antibodies, ~95% with full Fv sequence information and ~5% with solved structures. These datapoints originate from 100s of independent studies reported in either the academic literature or patent filings.

The entire contents CoV-AbDab database as of 2nd March 2021.
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How COVID-19 affected my (undergrad) masters

The COVID-19 pandemic hit us all in different ways, and this is a short look into how it affected me, a biochemistry undergrad doing my masters project in OPIG.

The first thing that impacted me was the move to working from home. Now you might think that as the group does only computational work that our work might not be too affected by working from home, as all the servers etc. can be accessed remotely. To a certain extent, this is true, it is possible to work from home for starters. Things may well be right as rain for a few people, but it wasn’t for me. I think a lot of people are finding that things take longer when not in the office even under the best circumstances. Technology and equipment can also reduce your productivity quite majorly. Not having a very fast computer (mine is 5 years old and you can tell) or poor chairs that give you backache (living that wooden dining room chair life) are just examples of things that affect your productivity, and also not something most of can do about.

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When antibodies go wrong: how antibodies can help viruses infect cells

I’ve been keeping up to date with the latest coronavirus vaccine developments using Derek Lowe’s blog, a resource which I cannot recommend highly enough. A recent post mentioned that vaccines developers are looking out for signs of antibody-dependent enhancement (ADE), which I vaguely remembered from my undergraduate biochemistry days researching an essay on dengue fever. ADE is an interesting immunology phenomenon, and so I thought I’d treat you all to a brief introduction to the issue.

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The Coronavirus Antibody Database (CoV-AbDab)

We are happy to announce the release of CoV-AbDab, our database tracking all coronavirus binding antibodies and nanobodies with molecular-level metadata. The database can be searched and downloaded here: http://opig.stats.ox.ac.uk/webapps/coronavirus

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Coronavirus

A zoonosis is an infectious disease that has jumped from a non-human animal to humans.

A painting by David S. Goodsell showing coronavirus in pink and purple. Secreted mucus (greenish threads) and antibodies (yellow/orange Y-shapes), and several small immune systems proteins (orange) from the lungs’ respiratory cells surround it. © 2020, David S. Goodsell.

The coronavirus disease 2019 (COVID-19) is one such zoonosis, and is caused by severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, SARS-CoV-2, or 2019-nCoV). This is very similar to the SARS virus that emerged in 2003. Its recent emergence has resulted in a WHO-declared public health emergency of international concern.

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