Acute treatment with monoclonal antibodies: their design and their use

Abstract

Passive anti-viral immunotherapy, including monoclonal antibodies (mAb), was identified early as a promising therapeutic avenue for COVID-19 with a rapid development pathway. This has been driven by the lack of existing effective direct acting antivirals for coronaviruses, the marginal clinical impact of remdesivir and the relative lack of efficacy of antivirals against other respiratory pathogens, combined with the failure of repurposed drugs. This review explores the potential utility of mAb targeting SARS-CoV-2, to prevent or treat COVID-19 infection. The use of mAb against host factors (e.g. tocilizumab targeting IL-6 receptor and canakinumab targeting IL1-β) to mitigate the inflammatory response seen in progressive disease will not be considered. This review will primarily consider mAb that have direct neutralising activity via their targeting of the SARS-CoV-2 Spike (S) protein focussing on: the targets of mAb; how they mediate viral neutralisation; their propensity to generate escape mutants; their clinical use so far, and their likely place in the therapeutic play book.