Recent outbreaks of Zika virus (ZIKV) highlight an urgent need for therapeutics.The protease complex NS2B-NS3 plays essential roles during flaviviral polyprotein processing, and thus represents an attractive drug target. Here, we developed a split luciferase complementation-based high-throughput screening assay to identify orthosteric inhibitors that directly target flavivirus NS2B-NS3 interactions. By screening a total of 2 816 approved and investigational drugs, we identified three potent candidates, temoporfin, niclosamide, and nitazoxanide, as flavivirus NS2B-NS3 interaction inhibitors with nanomolar potencies. Significantly, the most potent compound, temoporfin, not only inhibited ZIKV replication in human placental and neural progenitor cells, but also prevented ZIKV-induced viremia and mortality in mouse models. Structural docking suggests that temoporfin potentially binds NS3 pockets that hold critical NS2B residues, thus inhibiting flaviviral polyprotein processing in a non-competitive manner. As these drugs have already been approved for clinical use in other indications either in the USA or other countries, they represent promising and easily developed therapies for the management of infections by ZIKV and other flaviviruses.

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Background Real-time adherence monitoring is now possible through medication storage devices equipped with cellular technology. We assessed the effect of triggered cell phone reminders and counseling utilizing objective adherence data on antiretroviral (ART) adherence among Chinese HIV-infected patients. Methods We provided ART patients in Nanning, China, with a medication device (“Wisepill”) to monitor their ART adherence electronically. After 3 months, we randomized subjects within optimal (≥95%) and suboptimal (<95%) adherence strata to intervention vs. control arms. In months 4–9, intervention subjects received individualized reminders triggered by late dose-taking (no device-opening by 30 minutes past dose time), and counseling using device-generated data. Controls received no reminders or data-informed counseling. We compared post-intervention proportions achieving optimal adherence, mean adherence, and clinical outcomes. Results Of 120 subjects enrolled, 116 (96.7%) completed the trial. Pre-intervention, optimal adherence was similar in intervention vs. control arms (63.5% vs. 58.9%, respectively; p=0.60). In the last intervention month, 87.3% vs. 51.8% achieved optimal adherence (risk ratio (RR) 1.7, 95% Confidence Interval (CI) 1.3–2.2); mean adherence was 96.2% vs. 89.1% (p=0.003). Among pre-intervention suboptimal adherers, 78.3% vs. 33.3% (RR 2.4, CI 1.2–4.5) achieved optimal adherence; mean adherence was 93.3% vs. 84.7% (p=0.039). Proportions were 92.5% and 62.9% among optimal adherers, respectively (RR 1.5, CI 1.1–1.9); mean adherence was 97.8% vs. 91.7% (p=0.028). Post-intervention differences in clinical outcomes were not significant. Conclusion Real-time reminders significantly improved ART adherence in this population. This approach appears promising for managing HIV and other chronic diseases and warrants further investigation and adaptation in other settings.

Objective. Coronavirus disease 2019 (COVID-19) outbreak is a major challenge all over the world, without acknowledged treatment. Intravenous immunoglobulin (IVIG) has been recommended to treat critical coronavirus disease 2019 (COVID-19) patients in a few reviews, but the clinical study evidence on its efficacy in COVID-19 patients was lacking. Methods. 325 patients with laboratory-confirmed critical COVID-19 were enrolled from 4 government-designated COVID-19 treatment centres in southern China from December 2019 to March 2020. The primary outcomes were 28-and 60-day mortality, and the secondary outcomes were the total length of in-hospital and the total duration of the disease. Subgroup analysis was carried out according to clinical classification of COVID-19, IVIG dosage and timing. Results. In the enrolled 325 patients, 174 cases used IVIG and 151 cases did not. The 28-day mortality was improved with IVIG after adjusting confounding in overall cohort (P = 0.0014), and the in-hospital and the total duration of disease were longer in the IVIG group (P < 0.001). Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28-day mortality, decrease the inflammatory response and improve some organ functions (all P < 0.05); the application of IVIG in the early stage (admission ≤ 7 days) with a high dose (> 15 g per day) exhibited significant reduction in 60-day mortality in the critical-type patients. Conclusion. Early administration of IVIG with high dose