Capture and neutralization of SARS-CoV-2 and influenza virus by algae-derived lectins with high-mannose and core fucose specificities.

We first investigated the interactions between several algae-derived lectins and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We created lectin columns using high-mannose (HM)-type glycan-specific lectins OAA and KAA-1 or core fucose-specific lectin hypninA-2 and conducted binding experiments with SARS-CoV-2. The results showed that these lectins were capable of binding to the virus. Furthermore, when examining the neutralization ability of nine different lectins, it was found that KAA-1, ESA-2, and hypninA-2 were effective in neutralizing SARS-CoV-2. In competitive inhibition experiments with glycoproteins, neutralization was confirmed to occur through HM-type or core fucose-type glycans. However, neutralization was not observed with other lectins, such as OAA. This trend of KAA-1 and ESA-2 having the neutralizing ability and OAA not having it was also similar to influenza viruses. Electron microscopy observations revealed that KAA-1 and hypninA-2 strongly aggregated SARS-CoV-2 particles, while OAA showed a low degree of aggregation. It is believed that the neutralization of SARS-CoV-2 involves multiple factors, such as glycan attachment sites on the S protein, the size of lectins, and their propensity to aggregate, which cause inhibition of receptor binding or aggregation of virus particles. This study demonstrated that several algae-derived lectins could neutralize SARS-CoV-2 and that lectin columns can effectively recover and concentrate the virus.

Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement.

To combat infectious diseases, vaccines are considered the best prophylactic strategy for a wide range of the population, but even when vaccines are effective, the administration of therapeutic antibodies against viruses could provide further treatment options, particularly for vulnerable groups whose immunity against the viruses is compromised. Therapeutic antibodies against dengue are ideally engineered to abrogate binding to Fcγ receptors (FcγRs), which can induce antibody-dependent enhancement (ADE). However, the Fc effector functions of neutralizing antibodies against SARS-CoV-2 have recently been reported to improve post-exposure therapy, while they are dispensable when administered as prophylaxis. Hence, in this report, we investigated the influence of Fc engineering on anti-virus efficacy using the anti-dengue/Zika human antibody SIgN-3C and found it affected the viremia clearance efficacy against dengue in a mouse model. Furthermore, we demonstrated that complement activation through antibody binding to C1q could play a role in anti-dengue efficacy. We also generated a novel Fc variant, which displayed the ability for complement activation but showed very low FcγR binding and an undetectable level of the risk of ADE in a cell-based assay. This Fc engineering approach could make effective and safe anti-virus antibodies against dengue, Zika and other viruses.

Nanozyme: a New Approach for Anti-microbial Infections

Bacteria and viruses always posed a threat to human health. Most impressively, SARS-CoV-2 has raged around the world for almost three years, causing huge loss to human health. Facing increasing challenges of drug-resistance and poor treatment efficacy, new solutions are urgently needed to combat pathogenic microorganisms. Recently, nanozymes with intrinsic enzyme-like activities emerged as a promising new type of "antibiotics”. Nanozymes exhibit superior antibacterial and antiviral activities under physiological conditions by efficiently catalyzing generation of a large number of reactive oxygen species. Moreover, enhanced therapeutic effects are achieved in nanozyme-based therapy aided by the unique physicochemical properties of nanomaterials such as photothermal and photodynamic effects. This paper reviews the latest research progress in the field of anti-microbial nanozymes, systematically summarizes and analyzes the principles of nanozymes in the treatment of bacteria and viruses from a mechanistic point of view. An outlook on the future direction and the challenges of new anti-microbial infection nanomaterials are proposed to provide inspiration for developing next generation anti-microbial nanozymes. © 2023 Science Press. All rights reserved.

Delivery of spike-RBD by bacterial type three secretion system for SARS-CoV-2 vaccine development.

COVID-19 pandemic continues to spread throughout the world with an urgent demand for a safe and protective vaccine to effectuate herd protection and control the spread of SARS-CoV-2. Here, we report the development of a bacterial vector COVID-19 vaccine (aPA-RBD) that carries the gene for the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Live-attenuated strains of Pseudomonas aeruginosa (aPA) were constructed which express the recombinant RBD and effectively deliver RBD protein into various antigen presenting cells through bacterial type 3 secretion system (T3SS) in vitro. In mice, two-dose of intranasal aPA-RBD vaccinations elicited the development of RBD-specific serum IgG and IgM. Importantly, the sera from the immunized mice were able to neutralize host cell infections by SARS-CoV-2 pseudovirus as well as the authentic virus variants potently. T-cell responses of immunized mice were assessed by enzyme-linked immunospot (ELISPOT) and intracellular cytokine staining (ICS) assays. aPA-RBD vaccinations can elicit RBD-specific CD4+and CD8+T cell responses. T3SS-based RBD intracellular delivery heightens the efficiency of antigen presentation and enables the aPA-RBD vaccine to elicit CD8+T cell response. Thus, aPA vector has the potential as an inexpensive, readily manufactured, and respiratory tract vaccination route vaccine platform for other pathogens.

miRNAs derived from milk small extracellular vesicles inhibit porcine epidemic diarrhea virus infection.

Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus in the family Coronaviridae, causes acute diarrhea and/or vomiting, dehydration, and high mortality in neonatal piglets. It has caused huge economic losses to animal husbandry worldwide. Current commercial PEDV vaccines do not provide enough protection against variant and evolved virus strains. No specific drugs are available to treat PEDV infection. The development of more effective therapeutic anti-PEDV agents is urgently needed. Our previous study suggested that porcine milk small extracellular vesicles (sEV) facilitate intestinal tract development and prevent lipopolysaccharide-induced intestinal injury. However, the effects of milk sEV during viral infection remain unclear. Our study found that porcine milk sEV, which was isolated and purified by differential ultracentrifugation, could inhibit PEDV replication in IPEC-J2 and Vero cells. Simultaneously, we constructed a PEDV infection model for piglet intestinal organoids and found that milk sEV also inhibited PEDV infection. Subsequently, in vivo experiments showed that milk sEV pre-feeding exerted robust protection of piglets from PEDV-induced diarrhea and mortality. Strikingly, we found that the miRNAs extracted from milk sEV inhibited PEDV infection. miRNA-seq, bioinformatics analysis, and experimental verification demonstrated that miR-let-7e and miR-27b, which were identified in milk sEV targeted PEDV N and host HMGB1, suppressed viral replication. Taken together, we revealed the biological function of milk sEV in resisting PEDV infection and proved its cargo miRNAs, miR-let-7e and miR-27b, possess antiviral functions. This study is the first description of the novel function of porcine milk sEV in regulating PEDV infection. It provides a better understanding of milk sEV resistance to coronavirus infection, warranting further studies to develop sEV as an attractive antiviral.

Nature-Inspired Surface Structures Design for Antimicrobial Applications.

Surface contamination by microorganisms such as viruses and bacteria may simultaneously aggravate the biofouling of surfaces and infection of wounds and promote cross-species transmission and the rapid evolution of microbes in emerging diseases. In addition, natural surface structures with unique anti-biofouling properties may be used as guide templates for the development of functional antimicrobial surfaces. Further, these structure-related antimicrobial surfaces can be categorized into microbicidal and anti-biofouling surfaces. This review introduces the recent advances in the development of microbicidal and anti-biofouling surfaces inspired by natural structures and discusses the related antimicrobial mechanisms, surface topography design, material application, manufacturing techniques, and antimicrobial efficiencies.

Inorganic-based Surface Materials with Anti-SARS-CoV-2 Properties and Their Mechanisms of Action

The COVID-19 outbreak caused by SARS-CoV-2 has posed a serious threat to human health. The wide⁃ spread of the virus has increased the demand for anti-virus surface materials，especially in public places. This article reviews a series of inorganic surface materials with antiviral properties，including metals and its derivatives，graphene and its derivatives，and zeolites，and their antiviral mechanisms. The challenges and development prospects are summarized and prospected. © 2022 Higher Education Press. All rights reserved.

Towards building resilient cities to pandemics: A review of COVID-19 literature.

With the global prevalence of COVID-19 disease, the concept of urban resilience against pandemics has drawn the attention of a wide range of researchers, urban planners, and policymakers. This study aims to identify the major dimensions and principles of urban resilience to pandemics through a systematic review focused on lessons learned from the COVID-19 pandemic and comparing different perspectives regarding resilient urban environments to such diseases. Based on the findings, the study proposes a conceptual framework and a series of principles of urban resilience to pandemics, consisting of four spatial levels: housing, neighborhoods, city, and the regional and national scales, and three dimensions of pandemic resilience: pandemic-related health requirements, environmental psychological principles, and general resilience principles. The findings show that resilient cities should be able to implement the pandemic-related health requirements, the psychological principles of the environment to reduce the stresses caused by the pandemic, and the general principles of resilience in the smart city context. This framework provides scholars and policymakers with a comprehensive understanding of resilience on different scales and assists them in making better-informed decisions.

The effects of the recommended prescription for COVID-2019-lung-spleen qi deficiency on in vitro SARS-CoV-2 replication and pro-inflammatory factors expression

Aim To determine the antiviral and anti-inflammatory effects of the recommended prescription for COVID-2019-lung-spleen qi deficiency(4-1)against in vitro infection of SARS-CoV-2 and common coronaviruses.Methods The main chemical substances of 4-1 were analyzed by LC-MS.The toxicity and antiviral effects of of 4-1 were detected by MTT and by CPE assay, respectively.The viral loads in cell supernatant and the expression of inflammatory factors induced by viral infection were determined by qRT-PCR.Results The recommended prescription 4-1 contained 94 chemical compounds, including flavonoids, steroids, sesquiterpenoids, and so on.The range of selection indexes for SARS-CoV-2 and common coronaviruses was 8.44+/-0.49~52.26+/-2.3.This prescription could inhibit the proliferation of SARS-CoV-2, the expression of ACE2 and S mRNA, and down regulate IL-1alpha and CCL-5/RANTES at 10, 5, and 2.5 g*L-1 doses.Further, at doses of 20, 10 and 5 g*L-1, it could inhibit the proliferation of three common coronaviruses and suppress the overexpression of IL-6, CXCL-8/IL-8, CXCL-10/IP-10, TNF-alpha, IFN-alpha, CCL-2/MCP-1, MIG and CCL-5/RANTES induced by OC43/229E infection.The inhibitory effects were dose-dependent.Conclusions The prescription 4-1 has antiviral and anti-inflammation effects against multiple coronaviruses.This study provides the research basis for the treatment of common respiratory viral infections and emerging infectious diseases such as COVID-19 by using traditional Chinese medicine. Copyright © 2022 Publication Centre of Anhui Medical University. All rights reserved.

Sparking Nano-Metals on a Surface of Polyethylene Terephthalate and Its Application: Anti-Coronavirus and Anti-Fogging Properties.

The nano-metal-treated PET films with anti-virus and anti-fogging ability were developed using sparking nano-metal particles of Ag, Zn, and Ti wires on polyethylene terephthalate (PET) films. Ag nanoparticles were detected on the PET surface, while a continuous aggregate morphology was observed with Zn and Ti sparking. The color of the Ag-PET films changed to brown with increasing repeat sparking times, but not with the Zn-PET and Ti-PET films. The water contact angle of the nano-metal-treated PET films decreased with increasing repeat sparking times. The RT-PCR anti-virus test confirmed the high anti-virus efficiency of the nano-metal-treated PET films due to the fine particle distribution, high polarity, and binding of the nano-metal ions to the coronavirus, which was destroyed by heat after UV irradiation. A highly transparent, anti-fogging, and anti-virus face shield was prepared using the Zn-PET film. Sparking was an effective technique to prepare the alternative anti-virus and anti-fogging films for medical biomaterial applications because of their low cost, convenience, and fast processing.

Rethinking Outdoor Courtyard Spaces on University Campuses to Enhance Health and Wellbeing: The Anti-Virus Built Environment

Responding to the events surrounding the COVID-19 pandemic, this study explores how to improve health and wellbeing and reduce infections in outdoor open spaces on university campuses to maximize their potential as a response to future crises. The study identifies the relationship between human behavior (social) and the various physical and environmental elements of these spaces. A case study and mixed-methods approach were undertaken, comprising four modes of inspection: user analysis layer using questionnaires and observations to survey students’ needs and behavior;context analysis layer using space syntax and CFD to examine the space’s physical and environmental conditions;design solutions reflecting an understanding of virus transmission;and a performance analysis layer to test the performance of ‘anti-virus’ courtyards. The findings demonstrated that students are willing to use the open spaces that they used before the pandemic, at the same frequency. This indicates a need to redesign the current spaces to prevent the spread of viruses. The study highlights the social, physical, and environmental implications to be considered in designs for outdoor anti-virus spaces. It provides a comprehensive process for transforming outdoor spaces on university campuses into anti-virus spaces that meet users’ needs. These findings have implications for the designing and retrofitting of open spaces to reduce infection.

Detection of Exceptional Malware Variants Using Deep Boosted Feature Spaces and Machine Learning

Malware is a key component of cyber-crime, and its analysis is the first line of defence against cyber-attack. This study proposes two new malware classification frameworks: Deep Feature Space-based Malware classification (DFS-MC) and Deep Boosted Feature Space-based Malware classification (DBFS-MC). In the proposed DFS-MC framework, deep features are generated from the customized CNN architectures and are fed to a support vector machine (SVM) algorithm for malware classification, while, in the DBFS-MC framework, the discrimination power is enhanced by first combining deep feature spaces of two customized CNN architectures to achieve boosted feature spaces. Further, the detection of exceptional malware is performed by providing the deep boosted feature space to SVM. The performance of the proposed malware classification frameworks is evaluated on the MalImg malware dataset using the hold-out cross-validation technique. Malware variants like Autorun.K, Swizzor.gen!I, Wintrim.BX and Yuner.A is hard to be correctly classified due to their minor inter-class differences in their features. The proposed DBFS-MC improved performance for these difficult to discriminate malware classes using the idea of feature boosting generated through customized CNNs. The proposed classification framework DBFS-MC showed good results in term of accuracy: 98.61%, F-score: 0.96, precision: 0.96, and recall: 0.96 on stringent test data, using 40% unseen data.

Collection of the Main Anti-Virus Detection and Bypass Techniques

A large amount a new threats, technologies and business models have emerged in the cybersecurity area through the COVID-19 pandemic. The remote work involved unplanned cloud migrations and swift procurement of IT products and services the remote landscape. In this context, the role of anti-viruses is crucial for the private life and work. In this paper, we study the workings of anti-viruses as to understand how to avoid them. We created a collection of the main bypass techniques whilst analyzing their respective advantages and drawbacks. We show that it is possible to avoid both static and emulation analyses, while enunciating the techniques and approaches being used. © 2021, Springer Nature Switzerland AG.

Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates.

Lack of efficiency has been a major problem shared by all currently developed anti-SARS-CoV-2 therapies. Our previous study shows that SARS-CoV-2 structural envelope (2-E) protein forms a type of cation channel, and heterogeneously expression of 2-E channels causes host cell death. In this study we developed a cell-based high throughput screening (HTS) assay and used it to discover inhibitors against 2-E channels. Among 4376 compounds tested, 34 hits with cell protection activity were found. Followed by an anti-viral analysis, 15 compounds which could inhibit SARS-CoV-2 replication were identified. In electrophysiological experiments, three representatives showing inhibitory effect on 2-E channels were chosen for further characterization. Among them, proanthocyanidins directly bound to 2-E channel with binding affinity (KD) of 22.14 µM in surface plasmon resonance assay. Molecular modeling and docking analysis revealed that proanthocyanidins inserted into the pore of 2-E N-terminal vestibule acting as a channel blocker. Consistently, mutations of Glu 8 and Asn 15, two residues lining the proposed binding pocket, abolished the inhibitory effects of proanthocyanidins. The natural product proanthocyanidins are widely used as cosmetic, suggesting a potential of proanthocyanidins as disinfectant for external use. This study further demonstrates that 2-E channel is an effective antiviral drug target and provides a potential antiviral candidate against SARS-CoV-2.

Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential.

Curcumin, isolated from Curcuma longa L., is a fat-soluble natural compound that can be obtained from ginger plant tuber roots, which accumulative evidences have demonstrated that it can resist viral and microbial infection and has anti-tumor, reduction of blood lipid and blood glucose, antioxidant and removal of free radicals, and is active against numerous disorders various chronic diseases including cardiovascular, pulmonary, neurological and autoimmune diseases. In this article is highlighted the recent evidence of curcuminoids applied in sevral aspects of medical problem particular in COVID-19 pandemics. We have searched several literature databases including MEDLINE (PubMed), EMBASE, the Web of Science, Cochrane Library, Google Scholar, and the ClinicalTrials.gov website via using curcumin and medicinal properties as a keyword. All studies published from the time when the database was established to May 2021 was retrieved. This review article summarizes the growing confirmation for the mechanisms related to curcumin's physiological and pharmacological effects with related target proteins interaction via molecular docking. The purpose is to provide deeper insight and understandings of curcumin's medicinal value in the discovery and development of new drugs. Curcumin could be used in the prevention or therapy of cardiovascular disease, respiratory diseases, cancer, neurodegeneration, infection, and inflammation based on cellular biochemical, physiological regulation, infection suppression and immunomodulation.

A narrative review of COVID-19: magnesium isoglycyrrhizinate as a potential adjuvant treatment.

Coronavirus disease 2019 (COVID-19) has become a global pandemic affecting more than 200 countries with 87 million patients worldwide as of January 7, 2021. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replicates in a large amount and reaches high-titer levels in a short time after the infection. COVID-19 caused by SARS-CoV-2 shows clinical symptoms mainly including fever, fatigue, dry cough, and dyspnea. In more severe COVID-19 patients, viral pneumonia characterized by bilateral ground glass or patchy opacity, may lead to acute respiratory distress syndrome (ARDS), cytokine storm, multi-organ damage, and even death. Unfortunately, there is no effective therapy for COVID-19 until now. Magnesium isoglycyrrhizinate (MgIG), a magnesium salt of 18-α glycyrrhizic acid stereoisomer, belongs to the fourth generation of glycyrrhizic acid preparation. MgIG has various pharmacological activities including anti-inflammation, anti-oxidation, anti-virus, and immunoregulation, showing the protection against the injury of the vital organs (such as kidney, heart, and lung). Clinically, MgIG injection is usually used as a hepatoprotective agent to treat liver diseases. This narrative review summarizes the research and application of MgIG, and provides the evidence supporting the recommended MgIG as supportive therapy in the "Management Standard for Mild and Common Patients of Coronavirus Disease 2019 (COVID-19) (Second Edition)", which is jointly issued by National Health Commission of People's Republic of China and National Administration of Traditional Chinese Medicine.

The possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus （2019-nCov）pneumonia: a quick systematic review based on earlier coronavirus clinical studies / 中华急诊医学杂志

Objective@#To explore the possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus 2019-nCov pneumonia by systematically review earlier coronavirus studies.@*Methods @#Systematically retrieve relevant clinical studies from Chinese and English databases such as CNKI,VIP,Wangfang Data,CBM,PubMed, Web of Science,EMBASE. In addition, information from Chinese biomedical journals, WHO, US CDC, Chinese CDC websites and the references from published relevant articles were retrieved. The inclusion period is from January 2003 to January 24, 2020. The criteria for inclusion are:(1) studies that aim to compare LPV/r and placebo/standard for SARS, MERS; (2) studies that include at least one clinical outcome; (3) studies with diagnosis criteria meeting WHO requirement on SARS or MERS; (4)data from multiple reports but originated from one study, where we extract information from all reports; (5)guidelines, includes: national or academic guidelines/experts ‘consensus. The exclude criteria are: 1) only have abstracts but no full information; 2) in vitro studies. Two reviewers independently review articles and extract data on study design, patients, diagnosis criteria, regimen, and clinical outcomes (mortality, morbidity, quality of life, steroids dosage, chest image and adverse responses). @*Results@#Two hundred and thirty potential article were found by screening, and narrow down to forty-four articles for evaluation and fnally four studies were included. The results of included studies indicate the early use of LPV/r regimen can reduce the mortality of SARS and MERS, and reduce steroids dosing. @*Conclusions@#ILPV/r can be used as a component of experimental regimen for treat 2019-nCoV pneumonia. It strongly suggests that initiating real world studies to explore the true clinical effects of LPV/r on 2019-nCoV patients.