Evaluation of photocathode coupling-mediated hydroxychloroquine degradation in a single-chamber microbial fuel cell based on electron transfer mechanism and power generation

A photocathode-microbial electrochemical coupling system (PC-MFC) using black phosphorus-doped titanium dioxide nanobelt (BP/TB) as a photocatalyst is constructed for the degradation of hydroxychloroquine (HCQ, used to treat COVID-19). The degradation efficiency of HCQ (100 mg/L) in coupling system is 73.7% within 8 h, higher than that of photocatalysis (69.5%), MFC (25.6%), and adsorption (9.6%). The photocathode coupling facilitates subsequent bioelectric treatment, resulting in complete degradation of HCQ (100 mg/L) within 96 h in PC-MFC, much higher than in MFC (51.1%). Illumination of PC-MFC significantly increases the cathodic abundance of Pseudomonadales ord. (from 1.83% to 66.30%), accumulates biomass, improves the electrochemical behaviors of photocathode and bioanode, and finally increases the maximum power from 241 to 280 mW/m2. The electron transfer pathways depende on nicotinamide adenine dinucleotide dehydrogenase, succinate dehydrogenase and terminal oxidase. The coupled system enhances the dechlorination reduction of HCQ and reduces the biotoxicity of its degradation pathway. PC-MFC represents a new strategy for the treatment and energy recovery of refractory organic compounds in wastewater.

Intranasal delivery of replicating mRNA encoding hACE2-targeting antibody against SARS-CoV-2 Omicron infection in the hamster.

The Omicron variant is sweeping the world, which displays striking immune escape potential through mutations at key antigenic sites on the spike protein, making broad-spectrum SARS-CoV-2 prevention or therapeutical strategies urgently needed. Previously, we have reported a hACE2-targeting neutralizing antibody 3E8, which could efficiently block both prototype SARS-CoV-2 and Delta variant infections in prophylactic mouse models, having the potential of broad-spectrum to prevent SARS-CoV-2. However, preparation of monoclonal neutralizing antibodies is severely limited by the time-consuming process and the relative high cost. Here, we utilized a modified VEEV replicon with two subgenomic (sg) promoters engineered to express the light and heavy chains of the 3E8 mAb. The feasibility and protective efficacy of replicating mRNA encoding 3E8 against Omicron infection in the hamster were demonstrated through the lung targeting delivery with the help of VEEV-VRP. Overall, we developed a safe and cost-effective platform of broad-spectrum to prevent SARS-CoV-2 infection.

Photocatalytic degradation of COVID-19 related drug arbidol hydrochloride by Ti3C2 MXene/supramolecular g-C3N4 Schottky junction photocatalyst.

Because of the current COVID-19 outbreak all over the world, the problem of antiviral drugs entering water has become increasingly serious. Arbidol hydrochloride (ABLH) is one of the most widely used drugs against COVID-19, which has been detected in sewage treatment plant sediments after the COVID-19 outbreak. However, there has been no report on the degradation of ABLH. In order to remove ABLH we prepared a novel photocatalyst composed of Ti3C2 MXene and supramolecular g-C3N4 (TiC/SCN) via a simple method. The properties of the material were studied by a series of characterizations (SEM, TEM, EDS, XRD, FTIR, UV-vis, DRS, XPS, TPC, PL, EIS and UPS), indicating the successful preparation of TiC/SCN. Results show that 99% of ABLH was removed within 150 min under visible light illumination by the 0.5TiC/SCN (containing 0.5% of TiC). The performance of 0.5TiC/SCN was about 2.66 times that of SCN resulting from the formation of Schottky junction. Furthermore, under real sunlight illumination, 99.2% of ABLH could be removed by 0.5TiC/SCN within 120 min, which was better than that of commercial P25 TiO2. The pH, anions (NO3- and SO42-) and dissolved organic matter (fulvic acid) could significantly affect the ABLH degradation. Moreover, three possible degradation pathways of ABLH were proposed, and the toxicities of the corresponding by-products were less toxic than ABLH. Meanwhile, findings showed that the superoxide radicals played a major role in the photocatalytic degradation of ABLH by 0.5TiC/SCN. This study provides a well understanding of the mechanism of ABLH degradation and provides a valuable reference for the treatment of ABLH in water.

Berbamine hydrochloride potently inhibits SARS-CoV-2 infection by blocking S protein-mediated membrane fusion.

COVID-19 caused by SARS-CoV-2 has posed a significant threat to global public health since its outbreak in late 2019. Although there are a few drugs approved for clinical treatment to combat SARS-CoV-2 infection currently, the severity of the ongoing global pandemic still urges the efforts to discover new antiviral compounds. As the viral spike (S) protein plays a key role in mediating virus entry, it becomes a potential target for the design of antiviral drugs against COVID-19. Here, we tested the antiviral activity of berbamine hydrochloride, a bis-benzylisoquinoline alkaloid, against SARS-CoV-2 infection. We found that berbamine hydrochloride could efficiently inhibit SARS-CoV-2 infection in different cell lines. Further experiments showed berbamine hydrochloride inhibits SARS-CoV-2 infection by targeting the viral entry into host cells. Moreover, berbamine hydrochloride and other bis-benzylisoquinoline alkaloids could potently inhibit S-mediated cell-cell fusion. Furthermore, molecular docking results implied that the berbamine hydrochloride could bind to the post fusion core of SARS-CoV-2 S2 subunit. Therefore, berbamine hydrochloride may represent a potential efficient antiviral agent against SARS-CoV-2 infection.

Intranasal delivery of replicating mRNA encoding neutralizing antibody against SARS-CoV-2 infection in mice.

The lung is the prophylaxis target against SARS-CoV-2 infection, and neutralizing antibodies are a leading class of biological products against various infectious viral pathogen. In this study, we develop a safe and cost-effective platform to express neutralizing antibody in the lung with replicating mRNA basing on alphavirus replicon particle (VRP) delivery system, to prevent SARS-CoV-2 infections. First, a modified VEEV replicon with two subgenomic (sg) promoters was engineered to translate the light and heavy chains of antibody simultaneously, for expression and assembly of neutralizing anti-SARS-CoV-2 antibody CB6. Second, the feasibility and protective efficacy of replicating mRNA against SARS-CoV-2 infection were demonstrated through both in vitro and in vivo assays. The lung target delivery with the help of VRP system resulted in efficiently block SARS-CoV-2 infection with reducing viral titer and less tissue damage in the lung of mice. Overall, our data suggests that expressing neutralizing antibodies in the lungs with the help of self-replicating mRNA could potentially be a promising prophylaxis approach against SARS-CoV-2 infection.

ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker.

The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 "knock-in" mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and "alanine walk" studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and "broad-spectrum" management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.

SARS-CoV-2 replicon for high-throughput antiviral screening.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, which is highly pathogenic and classified as a biosafety level 3 (BSL-3) agent, has greatly threatened global health and efficacious antivirals are urgently needed. The high requirement of facilities to manipulate the live virus has limited the development of antiviral study. Here, we constructed a reporter replicon of SARS-CoV-2, which can be handled in a BSL-2 laboratory. The Renilla luciferase activity effectively reflected the transcription and replication levels of the replicon genome. We identified the suitability of the replicon in antiviral screening using the known inhibitors, and thus established the replicon-based high-throughput screening (HTS) assay for SARS-CoV-2. The application of the HTS assay was further validated using a few hit natural compounds, which were screened out in a SARS-CoV-2 induced cytopathic-effect-based HTS assay in our previous study. This replicon-based HTS assay will be a safe platform for SARS-CoV-2 antiviral screening in a BSL-2 laboratory without the live virus.

Protective Efficacy of Inactivated Vaccine against SARS-CoV-2 Infection in Mice and Non-Human Primates.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans.