Favipiravir and Zanamivir Cleared Infection with Influenza B in a Severely Immunocompromised Child

Abstract

A combination of favipiravir and zanamivir successfully cleared influenza B infection in a child who had undergone bone marrow transplant for X-linked severe combined immunodeficiency, with no recovery of T lymphocytes. Deep sequencing of viral samples illuminated the within-host dynamics of infection, demonstrating the effectiveness of favipiravir in this case.

A large effective population size for established within-host influenza virus infection

“…Here ΔD is a stochastic function describing the change in the population, measured according to the metric D, that arises from a single generation of genetic drift in a population with effective size N e and initial allele frequencies q(t 1 ). Regarding these allele frequencies we note that the distribution of minor allele frequencies across the genome was reasonably constant between samples for which a good read depth was achieved ( Figure 2S4; read depths for these data have previously been reported 32 ). To account for variance in these statistics we used different samples to initiate our simulations, reporting error bars across choices of q(t 1 ).…”

“…1A). Clinical details of the case, and the use of viral sequence data in evaluating the effectiveness of clinical intervention, have been described elsewhere 32 . After unsuccessful treatment with oseltamivir, zanamivir and nitazoxanide, a bone marrow transplant and favipiravir combination therapy led to the apparent clearance of infection.…”

“…Firstly, the model assumes that a linear model is appropriate to describe the change in the population over time; within our drift framework this is correct if the effective population size N e is constant, and if the distribution of allele frequencies does not change over time. In our data the consensus population declines approximately eight-fold 32 , then undergoes a bottleneck due to the influence of favipiravir; we infer a representative mean value of N, selecting for clade A only samples collected before the bottleneck. Secondly, our model assumes that the deviation from truth in our distance metric does not change in a manner that is systematically associated with the time between samples.…”

“…Sequence data describing the evolution of the infection was generated as part of a previous study 32 . Data…”

In Search for Effective and Safe Drugs Against SARS-CoV-2: Part I] Simulated Interactions Between Selected Nutraceuticals, ACE2 Enzyme and S Protein Simple Peptide Sequences

“…Taking in consideration the urgency of the current worldwide situation, repurposing preexisting drugs and nutraceuticals seems like a reasonable option [1]. For instance, drugs such as the antiviral favipiravir, which selectively inhibits RNA polymerase and prevents replication of the viral genome [2], the antimalarial hydroxychloroquine, which affects the binding of ACE2 and SARS-CoV2 spike protein, the antiparasitic ivermectin with nuclear transport inhibitory activity [3] and finally the anthelmintic niclosamide [4] have received attention as potential therapeutic agents tackling the virus through different mechanisms. Additionally, several well-known natural agents [5][6][7][8] such as curcumin, menthol, eriodictyol, thymoquinone, resveratrol, quercetin and raspberry ketone could potentially offer antiviral effects [9][10][11][12][13][14][15].…”