In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emerged to severely impact the global population, creating an unprecedented need for effective treatments. This study aims to investigate the potential of Scutellaria barbata D. Don (SB) as a treatment for SARS-CoV-2 infection through the inhibition of the proteases playing important functions in the infection by SARS-CoV-2. FRET assay was applied to investigate the inhibitory effects of SB on the two proteases involved in SARS-CoV-2 infection, M^pro and TMPRSS2. Additionally, to measure the potential effectiveness of SB treatment on infection inhibition, cellular models based on the Calu3 and VeroE6 cells and their TMPRSS2- expressing derivatives were assessed by viral pseudoparticles (Vpp) infection assays. The experimental approaches were conjugated with LC/MS analyses of the aqueous extracts of SB to identify the major constituent compounds, followed by a literature review to determine the potential active components of the inhibitory effects on protease activities. Our results showed that SB extracts inhibited the enzyme activities of M^pro and TMPRSS2. Furthermore, SB extracts effectively inhibited SARS-CoV-2 Vpp infection through a TMPRSS2-dependent mechanism. The aqueous extract analysis identified six major constituent compounds present in SB. Some of them have been known associated with inhibitory activities of TMPRSS2 or M^pro. Thus, SB may effectively prevent SARS-CoV-2 infection and replication through inhibiting M^pro and TMPRSS2 protease activities.

Asymmetric cell division (ACD) plays a pivotal role in development, tissue homeostasis, and stem cell maintenance. Emerging evidence suggests that long non-coding RNAs (lncRNAs) are key regulators of ACD, orchestrating the intricate molecular machinery that governs cell fate determination. This review summarizes current literature to elucidate the diverse roles of lncRNAs in modulating ACD across various biological contexts. The regulatory mechanisms of asymmetric cell division mediated by lncRNAs, including their interactions with protein effectors, epigenetic regulation, and subcellular localization are explored. Additionally, we discuss the implications of dysregulated lncRNAs in mediating ACD that lead to tumorigenesis. By integrating findings from diverse experimental models and cell types, this review provides insights into the multifaceted roles of lncRNAs in governing asymmetric cell division, shedding light on fundamental biological processes. Further research in this area may lead to the development of novel therapies targeting dysregulated lncRNAs to restore proper cell division and function. The knowledge of lncRNAs regulating ACD could potentially revolutionize the field of regenerative medicine and cancer therapy by targeting specific lncRNAs involved in ACD. By unraveling the complex interactions between lncRNAs and cellular processes, the potential novel opportunities for precision medicine approaches may be uncovered.

Targeting viral entry has been the focal point for the last 3 years due to the continued threat posed by SARS-CoV-2. SARS-CoV-2’s entry is highly dependent on the interaction between the virus’s Spike protein and host receptors. The virus’s Spike protein is a key modulator of viral entry, allowing sequential cleavage of ACE2 at the S1/S2 and S2 sites, resulting in the amalgamation of membranes and subsequent entry of the virus. A Polybasic insertion (PRRAR) conveniently located at the S1/S2 site can also be cleaved by furin or by serine protease, TMPRSS2, at the cell surface. Since ACE2 and TMPRSS2 are conveniently located on the surface of host cells, targeting one or both receptors may inhibit receptor-ligand interaction. Here, we show that Dauricine and Isoliensinine, two commonly used herbal compounds, were capable of inhibiting SARS-CoV-2 viral entry by reducing Spike-ACE2 interaction but not suppressing TMPRSS2 protease activity. Further, our biological assays using pseudoviruses engineered to express Spike proteins of different variants revealed a reduction in infection rates following treatment with these compounds. The molecular modeling revealed an interconnection between R403 of Spike protein and both two compounds. Spike mutations at residue R403 are critical, and often utilized by ACE2 to gain cell access. Overall, our findings strongly suggest that Dauricine and Isoliensinine are effective in blocking Spike-ACE2 interaction and may serve as effective therapeutic agents for targeting SARS-CoV-2′s viral entry.