Talk by David Ho on COVID-19

On Thursday David Ho gave a keynote lecture at the SMB conference. He talked about work to develop monoclonal antibodies against SARS-CoV-2. He started by apologising, in view of the given audience, that there would be no mathematics in his talk but he did make make clear his continuing belief in the importance of applying mathematics to biology. He has been leading an effort with a precise medical goal – to find effective neutralising antibodies against this new virus. Antibodies were obtained from five patients severely ill with COVID-19. Four of them survived while one later died of the disease. These antibodies were then analysed by biochemical and bioinformatic means to find those which bound best to the spike protein of the virus. In this context I learned some basic things about the virus. The spike, which is used by the virus to enter cells is considered the number one target for antibodies which could be effective in combating the disease. More precisely there are two different subdomains which are possible targets, one more at the tip of the spike (the receptor-binding domain) and another more on the sides (the N-terminal domain), which is a trimer. A number of antibodies were found which bind to the first subdomain or to one of the subunits of the second. Another was found whose binding site is somewhat less local. This whole process was carried out in just few weeks, a remarkable achievement.

The antibodies just mentioned are the therapeutic candidates. The idea is to either produce monoclonal antoibodies with these sequences or possibly versions which are improved so as to be longer-lived. Monoclonal antibodies are known to be extremely expensive when used to treat other diseases, such as cancer. They are also expensive in the present context, but the speaker said that the retail cost depends very much on the quantity produced. In other applications the number of patients is relatively small and the cost correspondingly high. If the antobodies were being used for a very large number of patients the cost would be lower. It would remain problematic for low and middle income countries. It has been discussed that the Gates foundation might make it possible to offer this treatment in poorer countries for fifty dollars a dose. The main advantage of this method compared with that of trying to use antibodies from the serum of patients directly is that it is much more practical to apply on a very large scale. The effectiveness of the antibodies against the disease has been tested in hamsters. Ho made the impression of someone tackling a major problem of humanity head on with some of the best tools available. He said that an article giving an account of the work had appeared in Nature (Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike, Nature 584, 450). In response to one question on one aspect of the treatment he said that the answer was not known but he would just be continuing to a Zoom meeting of researchers leading the attempts to develop therapies which was to discuss exactly that question.

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