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

to RDV in SARS CoV-1 which in turn leads to a less fit virus (22) . In the case of SARS Cov-1, two single mutations can induce to a less sensitive virus with 2.4-and 5.0-fold increase in the RDV EC50. When the combined mutations emerged, it mediated a 5.6-fold increase in the RDV EC50. We included these findings in the model by assuming that infected cells ( H ) that produce sensitive virus ( H ) can transition into infected cells ( I) and I8 ) that produce less sensitive virus ( I) and I8 ), due to one mutation during the viral replication cycle. These two viral populations have an increased EC50 (2.4-and 5-fold higher). Similarly, we assumed that I) and I8 can transition into infected cells that produce a more resistant strain I)8 (with 5.6-fold higher EC50) after another mutation. We also allowed for reversal mutation events. We assumed a mutation probability of = 10 2F per infection event. Under these assumptions total viral load is defined as = H + I) + I8 + I)8 and total number of infected cells as = H + I) + I8 + I) 8 . With these modifications the model becomes, . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.