Acriflavine and proflavine hemisulfate as potential antivirals by targeting Mpro.

The evolving SARS-CoV-2 epidemic buffets the world, and the concerted efforts are needed to explore effective drugs. M^pro is an intriguing antiviral target for interfering with viral RNA replication and transcription. In order to get potential anti-SARS-CoV-2 agents, we established an enzymatic assay using a fluorogenic substrate to screen the inhibitors of M^pro. Fortunately, Acriflavine (ACF) and Proflavine Hemisulfate (PRF) with the same acridine scaffold were picked out for their good inhibitory activity against M^pro with IC₅₀ of 5.60 ± 0.29 µM and 2.07 ± 0.01 µM, respectively. Further evaluation of MST assay and enzymatic kinetics experiment in vitro showed that they had a certain affinity to SARS-CoV-2 M^pro and were both non-competitive inhibitors. In addition, they inhibited about 90 % HCoV-OC43 replication in BHK-21 cells at 1 µM. Both compounds showed nano-molar activities against SARS-CoV-2 virus, which were superior to GC376 for anti-HCoV-43, and equivalent to the standard molecule remdesivir. Our study demonstrated that ACF and PRF were inhibitors of M^pro, and ACF has been previously reported as a PL^pro inhibitor. Taken together, ACF and PRF might be dual-targeted inhibitors to provide protection against infections of coronaviruses.

Reusable Cu2-xS-modified masks with infrared lamp-driven antibacterial and antiviral activity for real-time personal protection.

Disposable surgical masks are widely used by the general public since the onset of the coronavirus outbreak in 2019. However, current surgical masks cannot self-sterilize for reuse or recycling for other purposes, resulting in high economic and environmental costs. To solve these issue, herein we report a novel low-cost surgical mask decorated with copper sulfide (Cu2-xS) nanocrystals for photothermal sterilization in a short time (6 min). With the spun-bonded nonwoven fabrics (SNF) layer from surgical masks as the substrate, Cu2-xS nanocrystals are in-situ grown on their surface with the help of a commercial textile adhesion promoter. The SNF-Cu2-xS layer possesses good hydrophobicity and strong near infrared absorption. Under the irradiation with an infrared baking lamp (IR lamp, 50 mW cm-2), the surface temperature of SNF-Cu2-xS layer on masks can quickly increase to over 78 °C, resulting from the high photothermal effects of Cu2-xS nanocrystals. As a result, the polluted masks exhibit an outstanding antibacterial rate of 99.9999% and 85.4% for the Escherichia coli (E.coli) and Staphylococcus aureus (S. aureus) as well as the inactivation of human coronavirus OC43 (3.18-log10 decay) and influenza A virus A/PR/8/34 (H1N1) (3.93-log10 decay) after 6 min irradiation, and achieve rapid sterilization for reuse and recycling. Therefore, such Cu2-xS-modified masks with IR lamp-driven antibacterial and antiviral activity have great potential for real-time personal protection.

Ultra-fast bacterial inactivation of Cu2O@Halloysite nanotubes hybrids with charge adsorption and physical piercing ability for medical protective fabrics

Metals have been used for wound treatment and toxicity testing since ancient times. With the development of nanotechnology, metal oxides have been proven to have excellent sterilization and disinfection functions. However, the rapid bacterial inactivation efficiency and trapping physicochemical killing ability remain simultaneously undemonstrated in antibacterial nanohybrids. Here, we demonstrate a method for in-situ reduction of small-sized Cu2O particles on one-dimensional inorganic halloysite nanotubes (HNTs). The resultant Cu2O@HNTs hybrids not only give Cu2O excellent dispersibility, but also exert the synergistic effect of the charge adsorption of metal oxides and the physical piercing effect of the small-sized nanotubes. Furthermore, the release of Cu2+ from hybrids damages cell membranes and denatures proteins and DNA. Through this sterilization mechanism, Cu2O@HNTs allow for the inactivation rate of Escherichia coli to reach 94.5% within 2 min and complete inactivation within 10 min. This excellent sterilization mode makes Cu2O@HNTs exhibit excellent broad-spectrum antibacterial activity and inactivation efficiency, while shows weak cytotoxicity. These hybrids were further applied in the processing of functional antibacterial fibers and fabrics. Thus, we believe that this excellent antibacterial hybrid is practically attractive in this critical time of the COVID-19 pandemic.

The Analyses of High Infectivity Mechanism of SARS-CoV-2 and Its Variants

SARS-CoV-2 has high infectivity and some of its variants have higher transmissibility. To explore the high infectivity mechanism, the charge distributions of SARS-CoV, SARS-CoV-2, and variants of concern were calculated through a series of net charge calculation formulas. The results showed that the SARS-CoV-2 spike protein had more positive charges than that of SARS-CoV. Further results showed that the variants had similar but higher positive charges than preexisting SARS-CoV-2. In particular, the Delta variant had the greatest increase in positive charges in S1 resulting in the highest infectivity. In particular, the S1 positive charge increased greatly in the Delta variant. The S1 positive charge increased, and due to the large negative charge of angiotensin-converting enzyme-2 (ACE2), this resulted in a large increase in Coulomb’s force between S1 and ACE2. This finding agrees with the expectation that the positive charges in the spike protein result in more negative charges on SARS-CoV-2 antibodies than that of SARS-CoV. Thus, the infectivity of a novel SARS-CoV-2 variant may be evaluated preliminarily by calculating the charge distribution.