Potency and timing of antiviral therapy as determinants of duration of SARS CoV-2 shedding and intensity of inflammatory response

Ashish Goyal; E. Fabian Cardozo-Ojeda; Joshua T Schiffer

First, it is critical to know whether in vitro potency assessments of remdesivir, hydroxycholorquine and bNAbs can be projected onto human infection. We previously demonstrated that in vivo IC50 values for antiviral agents can exceed estimates derived from cell cultures experiments by a multiple of 5-10 for small molecule antiviral drugs (19) . A similar observation has been hypothesized for HIV targeting monoclonal neutralizing antibodies (23) . It is unclear if this discrepancy occurs due to low blood levels in tissue, different cell metabolism of drug in tissue or higher protein binding in vivo. Whatever the case, if in vitro potency measurements of hydroxycholoroquine and remdesivir overestimate in vivo activity, or if higher intracellular levels are required than in plasma, then these drugs may be less effective in clinical trials. Higher dosing may be a possible solution to circumvent this issue.