Background The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019 and there is no sign that the epidemic is abating . The major issue for controlling the infectious is lacking efficient prevention and therapeutic approaches. Chloroquine (CQ) and Hydroxychloroquine (HCQ) have been reported to treat the disease, but the underlying mechanism remains controversial. Purpose The objective of this study is to investigate whether CQ and HCQ could be ACE2 blockers and used to inhibit 2019-nCoV virus infection. Methods In our study, we used CCK-8 staining, flow cytometry and immunofluorescent staining to evaluate the toxicity and autophagy of CQ and HCQ, respectively, on ACE2 high-expressing HEK293T cells (ACE2 h cells). We further analyzed the binding character of CQ and HCQ to ACE2 by molecular docking and surface plasmon resonance (SPR) assays, 2019-nCoV spike pseudotyped virus was also used to observe the viropexis effect of CQ and HCQ in ACE2 h cells. Results Results showed that HCQ is slightly more toxic to ACE2 h cells than CQ. Both CQ and HCQ could bind to ACE2 with K D = (7.31 ± 0.62) e −7 M and (4.82 ± 0.87) e −7 M, respectively. They exhibit equivalent suppression effect for the entrance of 2019-nCoV spike pseudotyped virus into ACE2 h cells. Conclusions CQ and HCQ both inhibit the entrance 2019-nCoV into cells by blocking the binding of the virus with ACE2. Our findings provide novel insights into the molecular mechanism of CQ and HCQ treatment effect on virus infection.

Coronavirus Disease 2019 (COVID-19) cases and deaths are still rising worldwide, there is currently no effective treatment for severe inflammation and acute lung injury caused by new coronavirus (SARS-COV-2) infection. Therapies to prevent or treat COVID-19, including antiviral drug and several vaccines, are still being development. Human angiotensin-converting enzyme 2 (ACE2), expressing in lung, has been confirmed to be a receptor for SARS-COV-2 infection, interventions for attachment of spike protein of SARS-CoV-2 to ACE2 may be a potential approach to prevent viral infections and it is considered as a potential target for drug development. In this study, we observed that seabuckthorn and its flavonoid compounds quercetin and isorhamnetin were shown strong retention to ACE2 overexpression HEK293 (ACE2 h ) cells by CMC analysis. Based on drug receptor interaction analysis and viral entry studies in vitro, we evaluated the interaction of two flavonoid compounds and ACE2 as well as the inhibitory effect of the two compounds on viral entry. Surface plasmon resonance assay proved the effect that isorhamnetin bound to the ACE2, and its affinity (KD value) was at the micromolar level, that was, 2.51 ± 0.68 μM. Viral entry studies in vitro indicated that isorhamnetin inhibited SARS-CoV-2 spike pseudotyped virus entering ACE2 h cells. Based on promising in vitro results, we proposed isorhamnetin to be a potential therapeutic candidate compound against COVID-19.

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Glioma is an invasive brain cancer, and it is difficult to achieve desired therapeutic effects due to the high postoperative recurrence rate and limited efficacy of drug therapy hindered by the biological barrier of brain tissue. Nanodrug delivery systems are of great interest, and many efforts have been made to utilize them for glioma treatment. Polyamidoamine (PAMAM), a starburst dendrimer, provides malleable molecular size, functionalized molecular structure and penetrable brain barrier characteristics. Therefore, PAMAM-based nanodrug delivery systems (PAMAM DDS) are preferred for glioma treatment research. In this review, experimental studies on PAMAM DDS for glioma therapy were focused on and summarized. Emphasis was given to three major topics: methods of drug loading, linkers between drug/ligand and PAMAM and ligands of modified PAMAM. A strategy for well-designed PAMAM DDS for glioma treatment was proposed. Purposefully understanding the physicochemical and structural characteristics of drugs is necessary for selecting drug loading methods and achieving high drug loading capacity. Additionally, functional ligands contribute to achieving the brain targeting, brain penetration and low toxicity of PAMAM DDS. Furthermore, a brilliant linker facilitates multidrug combination and multifunctional PAMAM DDS. PAMAM DDS show excellent promise as drug vehicles and will be further studied for product development and safety evaluation.

The pandemic coronavirus COVID-19 affected global health from the end of 2019 to 2020 and may challenge global health in the future. There have been reports of Chloroquine (CQ) and Hydroxychloroquine (HCQ) used in clinical treatment. In our study, we used CCK-8 stain, flow cytometry and immunofluorescent stain to evaluated the toxicity and autophagy of CQ and HCQ respectively on ACE2 high expressed HEK293T cells (ACE2 hi cells). We further analysied the binding character of CQ and HCQ to ACE2 by molecular docking, surface plasmon resonance (SPR) assays and molecule docking, COVID-19 spike pseudotype virus was also taken to investigate the suppression viropexis effect of CQ and HCQ. Results showed that HCQ is slightly more toxic to ACE2 hi cells than CQ, both CQ and HCQ could bind to ACE2, and they also exhibit equivalent suppression effect for the entrance of COVID-19 Spike pseudotype virus into ACE2 hi cells. Our finding provides a theoretical and experimental basis for the clinical treatment of CQ and HCQ for COVID-19.