Success of prophylactic antiviral therapy for SARS-CoV-2: Predicted critical efficacies and impact of different drug-specific mechanisms of action

Repurposed drugs that are safe and immediately available constitute a first line of defense against new viral infections. Despite limited antiviral activity against SARS-CoV-2, several drugs are being tested as medication or as prophylaxis to prevent infection. Using a stochastic model of early phase infection, we evaluate the success of prophylactic treatment with different drug types to prevent viral infection. We find that there exists a critical efficacy that a treatment must reach in order to block viral establishment. Treatment by a combination of drugs reduces the critical efficacy, most effectively by the combination of a drug blocking viral entry into cells and a drug increasing viral clearance. Below the critical efficacy, the risk of infection can nonetheless be reduced. Drugs blocking viral entry into cells or enhancing viral clearance reduce the risk of infection more than drugs that reduce viral production in infected cells. The larger the initial inoculum of infectious virus, the less likely is prevention of an infection. In our model, we find that as long as the viral inoculum is smaller than 10 infectious virus particles, viral infection can be prevented almost certainly with drugs of 90% efficacy (or more). Even when a viral infection cannot be prevented, antivirals delay the time to detectable viral loads. The largest delay of viral infection is achieved by drugs reducing viral production in infected cells. A delay of virus infection flattens the within-host viral dynamic curve, possibly reducing transmission and symptom severity. Thus, antiviral prophylaxis, even with reduced efficacy, could be efficiently used to prevent or alleviate infection in people at high risk. Author summary Antiviral therapy taken prophylactically can prevent a viral infection. Administering antiviral drugs in prophylaxis to health care workers or other people at risk could be especially important in the SARS-CoV-2 pandemic. Monoclonal antibodies against the SARS-CoV-2 spike protein and small molecule antiviral drugs could be used for pre- or post-exposure prophylaxis. We predict that combination therapy with two drugs with different modes of action and enough efficacy have the potential to fully prevent SARS-CoV-2 infection. We provide a prediction for the critical combination of drug efficacies above which viral establishment is suppressed entirely. Prophylactic antiviral therapy could be feasible, efficient, and alleviate the burden on healthcare systems.