Author: Ashish Goyal; E. Fabian Cardozo-Ojeda; Joshua T Schiffer
Title: Potency and timing of antiviral therapy as determinants of duration of SARS CoV-2 shedding and intensity of inflammatory response Document date: 2020_4_14
ID: d7stppv5_28
Snippet: Based on the mutation rate of positive ss RNA viruses of approximately 10 -5 mutations per base pair per cell infection (21) , and on the fact that two separate mutations may induce partial remdesivir resistance in SARS CoV-1 which in turn leads to a less fit virus (22) , we estimated the probability that a drug resistant mutant would emerge during therapy. When we assumed a potent therapy (EC50=0.8), the model projects that while single and doub.....
Document: Based on the mutation rate of positive ss RNA viruses of approximately 10 -5 mutations per base pair per cell infection (21) , and on the fact that two separate mutations may induce partial remdesivir resistance in SARS CoV-1 which in turn leads to a less fit virus (22) , we estimated the probability that a drug resistant mutant would emerge during therapy. When we assumed a potent therapy (EC50=0.8), the model projects that while single and double mutants will emerge, they are unlikely to predominate or meaningfully extend duration of shedding if dosed during the symptomatic phase of disease, though resistance may emerge with early dosing (Fig. 6a,b) . However, if a moderate potency is assumed, then a single mutant with resistant is predicted to persist, particularly if therapy is initiated before or during viral peak (Fig. 7a,b) .
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