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Neutralizing monoclonal antibodies (mAb), novel therapeutics for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), have been urgently researched from the start of the pandemic. The selection of the optimal mAb candidate and therapeutic dose were expedited using open-access in silico models. The maximally effective therapeutic mAb dose was determined through two approaches; both expanded on innovative, open-science initiatives. A physiologically-based pharmacokinetic (PBPK) model, incorporating physicochemical properties predictive of mAb clearance and tissue distribution, was used to estimate mAb exposure that maintained concentrations above 90% inhibitory concentration of in vitro neutralization in lung tissue for up to 4 weeks in 90% of patients. To achieve fastest viral clearance following onset of symptoms, a longitudinal SARS-CoV-2 viral dynamic model was applied to estimate viral clearance as a function of drug concentration and dose. The PBPK model-based approach suggested that a clinical dose between 175 and 500 mg of bamlanivimab would maintain target mAb concentrations in the lung tissue over 28 days in 90% of patients. The viral dynamic model suggested a 700 mg dose would achieve maximum viral elimination. Taken together, the first-in-human trial (NCT04411628) conservatively proceeded with a starting therapeutic dose of 700 mg and escalated to higher doses to evaluate the upper limit of safety and tolerability. Availability of open-access codes and application of novel in silico model-based approaches supported the selection of bamlanivimab and identified the lowest dose evaluated in this study that was expected to result in the maximum therapeutic effect before the first-in-human clinical trial.

Proceedings of the Sixth Annual Meeting of the Berkeley Linguistics Society (1980), pp. 180-190

The Huichol Indians of the State of Jalisco, Mexico, are best known among ethnobotanists and anthropologists for their use of the small hallucinogenic cactus, which they call /hikuli/, more commonly known as peyote (Lophophora Williamsii). Each year around December begins their complex re-enactment of the primordial mythological quest for the peyote that takes them on a pilgrimage to the deserts of San Luis Potosi near Real de la Catorce in search of the Peyote. This pilgrimage is the core of the symbolic-religious complex central to the lives of almost 10,000 Huicholes. The quest lasts only one month or so, but it is of paramount importance to all other socio-religious activity within the Huichol comunidades throughout the

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