Harringtonine: A more effective antagonist for Omicron variant.

Fusion with host cell membrane is the main mechanism of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we propose that a new strategy to screen small-molecule antagonists blocking SARS-CoV-2 membrane fusion. Using cell membrane chromatography (CMC), we found that harringtonine (HT) simultaneously targeted SARS-CoV-2 S protein and host cell surface TMPRSS2 expressed by the host cell, and subsequently confirmed that HT can inhibit membrane fusion. HT effectively blocked SARS-CoV-2 original strain entry with the IC50 of 0.217 µM, while the IC50 in delta variant decreased to 0.101 µM, the IC50 in Omicron BA.1 variant was 0.042 µM. Due to high transmissibility and immune escape, Omicron subvariant BA.5 has become the dominant strain of the SARS-CoV-2 virus and led to escalating COVID-19 cases, however, against BA.5, HT showed a surprising effectiveness. The IC50 in Omicron BA.5 was even lower than 0.0019 µM. The above results revealed the effect of HT on Omicron is very significant. In summary, we characterize HT as a small-molecule antagonist by direct targeting on the Spike protein and TMPRSS2.

Individual Surveillance Around Parked Aircraft at Nighttime: Thermal Infrared Vision-Based Human Action Recognition

The COVID-19 crisis has led to an unusually large number of commercial aircraft being currently parked or stored. For airlines, airports, and civil aviation authorities around the world, monitoring, and protecting these parked aircraft to prevent them from causing human-made damage are becoming urgent problems that are receiving increasing attention. In this study, we use thermal infrared monitoring videos to establish a framework for individual surveillance around parked aircraft by proposing a human action recognition (HAR) algorithm. As the focus of this article, the proposed HAR algorithm seamlessly integrates a preprocessing module in which a novel data structure is constructed to introduce spatiotemporal information of the action;a convolutional neural network-based module for spatial feature extraction;a triple-layer convolutional long short-term memory network for temporal feature extraction;and two fully connected layers for classification. Moreover, because no infrared dataset is available for the HAR task on airport grounds at nighttime, we present a dataset called IIAR-30, which consists of eight action categories that frequently occur on airport grounds and 2000 video clips. The experimental results on the IIAR-30 dataset demonstrated that the recognition accuracy of the proposed method was higher than 96%. We also further evaluated the effectiveness of the proposed method by comparing it with five baselines and four other methods.

Molecular detection of SARS-CoV-2 being challenged by virus variation and asymptomatic infection.

Coronavirus disease 2019 (COVID-19) has been a pandemic for more than a year. With the expanding second wave of the pandemic in winter, the continuous evolution of SARS-CoV-2 has brought new issues, including the significance of virus mutations in infection and the detection of asymptomatic infection. In this review, we first introduced several major SARS-CoV-2 mutations since the COVID-19 outbreak and then mentioned the widely used molecular detection techniques to diagnose COVID-19, primarily focusing on their strengths and limitations. We further discussed the effects of viral genetic variation and asymptomatic infection on the molecular detection of SARS-CoV-2 infection. The review finally summarized useful insights into the molecular diagnosis of COVID-19 under the special situation being challenged by virus mutation and asymptomatic infection.

Oroxylin A is a severe acute respiratory syndrome coronavirus 2-spiked pseudotyped virus blocker obtained from Radix Scutellariae using angiotensin-converting enzyme II/cell membrane chromatography.

The current worldwide outbreak of the coronavirus disease 2019 (COVID-19) has been declared a public health emergency. The angiotensin-converting enzyme II (ACE2) has been reported as the primary host-cell receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of COVID-19. In this study, we screened ACE2 ligands from Radix Scutellariae and investigated its suppressive effect on SARS-CoV-2 spiked pseudotyped virus in vitro. HEK293T cells stably expressing ACE2 receptors (ACE2 cells) were used to provide the receptor for the ACE2/cell membrane chromatography (CMC) method used for analysis. The SARS-CoV-2-spiked pseudotyped virus was used to examine the anti-viropexis effect of the screened compounds in ACE2 cells. Molecular docking and the surface plasmon resonance (SPR) assay were used to determine the binding properties. Oroxylin A exhibited an appreciable suppressive effect against the entrance of the SARS-CoV-2-spiked pseudotyped virus into ACE2 cells, which showed good binding to ACE2 as determined using SPR and CMC. Oroxylin A was shown to be a potential candidate in the treatment for COVID-19 by virtue of its blocking the entrance of SARS-CoV-2 into ACE2 cells by specifically binding to the ACE2 receptor.

Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus.

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 (ACE2h 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 ACE2h cells. RESULTS: Results showed that HCQ is slightly more toxic to ACE2h cells than CQ. Both CQ and HCQ could bind to ACE2 with KD = (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 ACE2h 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.