https://researchopenworld.com/towards-covid-19-prophylaxis-an-aids-preclinical-research-perspective/#

Abstract

Remdesivir, a nucleoside analogue specific for the RNAdependent RNA polymerase of several coronaviruses, is a potent SARS-CoV-2 antiviral drug based on studies in vitro. Its half maximal effective concentration (EC50) leans consistently towards the lowest estimates when screened, using the same assay, with other antivirals tested against several coronaviruses [1-4] hence, a relatively lower concentration of the drug is needed to cut similar levels of viral replication in vitro, compared to other antiviral drugs less successfully repurposed, so far, as medical countermeasures against COVID-19. These include the HIV-1 protease inhibitor lopinavir/ritonavir (Kaletra) and the immunosuppressive and anti-parasitic drug hydroxychloroquine [5,6]. The success of an antiviral drug in fighting a virus depends, however, not only on how potent the drug is in inhibiting the virus in vitro but also on how well the drug penetrates the anatomic compartments in which the virus mostly replicates in vivo; the lungs

Viral dissemination and immune activation modulate antiretroviral drug levels in lymph nodes of SIV-infected rhesus macaques

“…Here we observed an increase in the concentration of NRTIs active moieties (IADM) in both lymph nodes and PB between months 1 and 3 of ART, and an inverse association between viral dissemination in plasma/tissues (both LN and rectal tissue) at ART initiation and IADM levels at one month into ART. As NRTIs need to sequentially phosphorylate inside cells by host enzymes to their pharmacologically active triphosphates, we suggest that this inverse association has broad implications for drugs that need to be phosphorylated to exert their pharmacological activity, especially in the settings of pre- or post-exposure prophylaxis targeting highly virulent pathogens replicating in anatomic compartments characterized by high levels of inflammation, such as rectal\vaginal tissues of Truvada-PREP recipients with a high risk of contracting HIV infection ( 34 , 35 ), or the lungs of Remdesivir\Molnupiravir recipients for the treatment of SARS-CoV-2 infection ( 36 – 39 ).…”