Towards COVID-19 Prophylaxis: An AIDS Preclinical Research Perspective.

Abstract

The success of an antiviral drug depends on its potency to neutralize the virus in vitro and its ability after administration in vivo to reach the anatomic compartments that fuel viral dissemination in the body. For instance, remdesivir, a potent SARS-CoV-2 antiviral drug based on studies in vitro, if administered orally would be poorly effective because low drug levels would reach the lungs due to its high first pass destruction in the liver. This is the reason remdesivir can only be administered intravenously, a requirement that clearly limits its use as a prophylactic agent for COVID-19, although novel formulations for its easier administration are under development. Whether an antiviral prophylaxis could further control or even stop the COVID-19 epidemic in synergy with other non-pharmacological based mitigation strategies is today unknown. Since the mid-1960s, pharmacologists have investigated the use of lipid-based nanoparticles for efficient delivery of antivirals to tissues, for example by transforming the route of administration from intravenous to oral, subcutaneous or aerosol administrations. These novel encapsulation strategies have also the potential to maintain high levels of the antiviral drugs in tissues, with reduced dose frequency compared to the non-encapsulated drug. Several lipid-based nanoparticles are today approved by the US Food and Drug Administration or being tested in clinical studies with favorable toxicity profiles. Nonhuman primate models of coronavirus infection offer unique platforms to accelerate the search for SARS-CoV-2 antiviral prophylaxis. Paradigms, to corroborate this claim, are borrowed from nonhuman primate research studies, some of which had a profound impact on global public health in the specific setting of the AIDS pandemic. Sharing information from nonhuman primate research programs, invoking principles of scientific transparency and bioethics similar to those universally agreed for human studies, would also likely significantly help our collective fight (as the human species) against this public health emergency.