Articles: pandemics.
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Emerging coronaviruses (CoVs) cause severe disease in humans, but no approved therapeutics are available. The CoV nsp14 exoribonuclease (ExoN) has complicated development of antiviral nucleosides due to its proofreading activity. We recently reported that the nucleoside analogue GS-5734 (remdesivir) potently inhibits human and zoonotic CoVs in vitro and in a severe acute respiratory syndrome coronavirus (SARS-CoV) mouse model. ⋯ Following selection with the GS-5734 parent nucleoside, 2 amino acid substitutions in the nsp12 polymerase at residues that are identical across CoVs provide low-level resistance to GS-5734. The resistance mutations decrease viral fitness of MHV in vitro and attenuate pathogenesis in a SARS-CoV animal model of infection. Together, these studies define the target of GS-5734 activity and demonstrate that resistance is difficult to select, only partial, and impairs fitness and virulence of MHV and SARS-CoV, supporting further development of GS-5734 as a potential effective pan-CoV antiviral.
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The goal of ending the HIV/AIDS pandemic is theoretically achievable and would require addressing this global health catastrophe on individual and global levels by providing optimal prevention strategies and treatment regimens for individual persons living with or at risk for HIV, as well as ending the pandemic as an epidemiologic and global health phenomenon. However, from a practical standpoint, the pathway to ending the HIV/AIDS pandemic will be difficult and will require aggressive implementation of the biomedical research advances that have been made in the areas of treatment and prevention; development of additional tools, such as a moderately effective HIV vaccine; and attention to critical behavioral and social determinants. An end to the HIV/AIDS pandemic can be achieved only with provision of sustained and additional resources at the local, regional, national, and global levels.
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Pandemics of new and emerging infectious diseases are unpredictable, recurrent events that rapidly threaten global health and security. We aimed to identify public views regarding provision of information and consent to participate in primary and critical care clinical research during a future influenza-like illness pandemic. ⋯ This bottom-up approach to ascertaining public views on pandemic clinical research has identified support for more proportionate research protection procedures for publically funded, low-risk studies.