Tunneling Nanotubes: The Cables for Viral Spread and Beyond.

Multicellular organisms require cell-to-cell communication to maintain homeostasis and thrive. For cells to communicate, a network of filamentous, actin-rich tunneling nanotubes (TNTs) plays a pivotal role in facilitating efficient cell-to-cell communication by connecting the cytoplasm of adjacent or distant cells. Substantial documentation indicates that diverse cell types employ TNTs in a sophisticated and intricately organized fashion for both long and short-distance communication. Paradoxically, several pathogens, including viruses, exploit the structural integrity of TNTs to facilitate viral entry and rapid cell-to-cell spread. These pathogens utilize a "surfing" mechanism or intracellular transport along TNTs to bypass high-traffic cellular regions and evade immune surveillance and neutralization. Although TNTs are present across various cell types in healthy tissue, their magnitude is increased in the presence of viruses. This heightened induction significantly amplifies the role of TNTs in exacerbating disease manifestations, severity, and subsequent complications. Despite significant advancements in TNT research within the realm of infectious diseases, further studies are imperative to gain a precise understanding of TNTs' roles in diverse pathological conditions. Such investigations are essential for the development of novel therapeutic strategies aimed at leveraging TNT-associated mechanisms for clinical applications. In this chapter, we emphasize the significance of TNTs in the life cycle of viruses, showcasing the potential for a targeted approach to impede virus-host cell interactions during the initial stages of viral infections. This approach holds promise for intervention and prevention strategies.

Significance of Artificial Intelligence in the Study of Virus-Host Cell Interactions.

A highly critical event in a virus's life cycle is successfully entering a given host. This process begins when a viral glycoprotein interacts with a target cell receptor, which provides the molecular basis for target virus-host cell interactions for novel drug discovery. Over the years, extensive research has been carried out in the field of virus-host cell interaction, generating a massive number of genetic and molecular data sources. These datasets are an asset for predicting virus-host interactions at the molecular level using machine learning (ML), a subset of artificial intelligence (AI). In this direction, ML tools are now being applied to recognize patterns in these massive datasets to predict critical interactions between virus and host cells at the protein-protein and protein-sugar levels, as well as to perform transcriptional and translational analysis. On the other end, deep learning (DL) algorithms-a subfield of ML-can extract high-level features from very large datasets to recognize the hidden patterns within genomic sequences and images to develop models for rapid drug discovery predictions that address pathogenic viruses displaying heightened affinity for receptor docking and enhanced cell entry. ML and DL are pivotal forces, driving innovation with their ability to perform analysis of enormous datasets in a highly efficient, cost-effective, accurate, and high-throughput manner. This review focuses on the complexity of virus-host cell interactions at the molecular level in light of the current advances of ML and AI in viral pathogenesis to improve new treatments and prevention strategies.

Indian Society of Periodontology Good Clinical Practice Recommendations for Peri-implant Care.

Current implant therapy is a frequently employed treatment for individuals who have lost teeth, as it offers functional and biological advantages over old prostheses. Concurrently, active exploration of intervention strategies aims to prevent the progression of peri-implant diseases and manage the existing peri-implant tissue damage. Indian Society of Periodontology has recognized the need for systematic documents to update the everyday clinical practice of general dental practitioners and has provided evidence-based consensus documents, namely good clinical practice recommendations from time to time to raise the oral health-related awareness and standards of oral health-care delivery across the country. The current clinical practice recommendations focused on peri-implant care to bridge the gap between academic theory and clinical practice by compiling evidence-based suggestions for preventing and treating peri-implant diseases. Twenty-eight subject experts across the country prepared these recommendations after a thorough literature review and group discussions. The document has been prepared in three sections covering peri-implant health and maintenance, peri-implant mucositis, and peri-implantitis. It will be a quick and concise reference for oral implant practitioners in patient management. The guidelines provide distinct definitions, signs, and symptoms, treatment required; recall visit specifications for plausible clinical case situations, and home-care recommendations regarding maintaining peri-implant health. The document advocates combined efforts of oral implant practitioners and the population at large with evidence-based, integrated, and comprehensive peri-implant care. By providing accessible, applicable guidance, these guidelines would empower dental professionals to uphold the well-being of implant patients and ensure the long-term success of implant therapy.

Clinicopathologic Spectrum and Outcomes of Infections Diagnosed on Graft Biopsies and Nephrectomy in Live Renal Allograft Recipients: An Institutional Experience.

OBJECTIVES: Modern immunosuppressive regimens have reduced rejection episodes in renal allograft recipients but have increased the risk of opportunistic infections. Infections are considered to be the second leading cause of death after cardiovascular complications in renal allograft recipients. Data on opportunistic infections affecting the allograft itself are scarce. The present study describes the spectrum of renal opportunistic infections and their outcomes diagnosed on renal allograft biopsies and nephrectomy specimens. MATERIALS AND METHODS: Our retrospective observational study was conducted from December 2011 to December 2021. We analyzed infectious episodes diagnosed on renal allograft biopsies or graft nephrectomy specimens. We obtained clinical, epidemiological, and laboratory details for analyses from hospital records. RESULTS: BK virus nephropathy was the most common opportunistic infection affecting the allograft, accounting for 47% of cases, followed by bacterial graft pyelonephritis (25%). Mucormycosis was the most common fungal infection. The diagnosis of infection from day of transplant ranged from 14 days to 39 months. Follow-up periods ranged from 1 to 10 years. Mortality was highest among patients with opportunistic fungal infection (62%), followed by viral infections, and graft failure rate was highest in patients with graft pyelonephritis (50%). Among patients with BK polyomavirus nephropathy, 45% had stable graft function compared with just 33% of patients with bacterial graft pyelonephritis. CONCLUSIONS: BK polyoma virus infection was the most common infection affecting the renal allograft in our study. Although fungal infections caused the highest mortality among our patients, bacterial graft pyelonephritis was responsible for maximum graft failure. Correctly identifying infections on histology is important so that graft and patient life can be prolonged.

ABO-Incompatible Renal Transplant: A Single-Center Experience from India.

Introduction: In view of ever-increasing end-stage renal disease (ESRD) population but inadequate availability of suitable donors, ABO-incompatible (ABOi) transplantation can be an important void filler. However, at present, ABOi transplantation is limited to a few centers in India and there is a lack of adequate experience and expertise to guide this program to other centers in the country. Methods: Data of all the ABOi transplants performed from 2012 to 2021 in a tertiary care hospital was retrospectively analyzed. The anti-ABO antibody (IgG) titers (≤1:4) were considered safe before transplantation. Desensitization included rituximab, plasma exchange, or selective immunoadsorption column. Tacrolimus and mycophenolate mofetil were initiated at day -7. Induction agents included ATG, ATLG, basiliximab, or no induction. Postoperatively, anti-ABO titers were done daily for 2 weeks. Results: A total of 202 patients underwent transplantation; of these, 195 patients whose data were for available for 12 months were included in the study. Mean duration of follow-up was 28.9 ± 21.7 months. UTI was the most common source of infection, occurring in almost half (46.1%) of the patients. Antibody-mediated rejection (ABMR; 15%) was common in the first year. Patient survival was 86.6% (169/195) at 1 year. Sepsis was the most common of death in more than two-thirds of the population, including coronavirus disease 2019 (COVID-19)-associated mortality in nine patients (4.6%). Death-censored graft survival was 89.3% (174/195). AMR was the leading cause of graft loss in almost half of the patients. Conclusion: ABOi should be considered in ESRD patients for whom suitable ABO-compatible donor is not available. Higher rate of rejection and infection are still a major concern.

Co-Expression of Niemann-Pick Type C1-Like1 (NPC1L1) with ACE2 Receptor Synergistically Enhances SARS-CoV-2 Entry and Fusion.

The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human embryonic kidney (HEK293T) cells has been shown to be a cholesterol-rich, lipid raft-dependent process. In this study, we investigated if the presence of a cholesterol uptake receptor Niemann-pick type c1-like1 (NPC1L1) impacts SARS-CoV-2 cell entry. Initially, we utilized reporter-based pseudovirus cell entry assays and a spike (S) glycoprotein-mediated cell-to-cell fusion assay. Using Chinese hamster ovary (CHO-K1) cells, which lack endogenous receptors for SARS-CoV-2 entry, our data showed that the co-expression of NPC1L1 together with the ACE2 receptor synergistically increased SARS-CoV-2 pseudovirus entry even more than the cells expressing ACE-2 receptor alone. Similar results were also found with the HEK293T cells endogenously expressing the ACE2 receptor. Co-cultures of effector cells expressing S glycoprotein together with target cells co-expressing ACE-2 receptor with NPC1L1 significantly promoted quantitative cell-to-cell fusion, including syncytia formation. Finally, we substantiated that an elevated expression of NPC1L1 enhanced entry, whereas the depletion of NPC1L1 resulted in a diminished SARS-CoV-2 entry in HEK293T-ACE2 cells using authentic SARS-CoV-2 virus in contrast to their respective control cells. Collectively, these findings underscore the pivotal role of NPC1L1 in facilitating the cellular entry of SARS-CoV-2. Importance: Niemann-Pick type C1-like1 (NPC1L1) is an endosomal membrane protein that regulates intracellular cholesterol trafficking. This protein has been demonstrated to play a crucial role in the life cycle of several clinically important viruses. Although SARS-CoV-2 exploits cholesterol-rich lipid rafts as part of its viral entry process, the role of NPC1L1 in SARS-CoV-2 entry remains unclear. Our research represents the first-ever demonstration of NPC1L1's involvement in facilitating SARS-CoV-2 entry. The observed role of NPC1L1 in human kidney cells is not only highly intriguing but also quite relevant. This relevance stems from the fact that NPC1L1 exhibits high expression levels in several organs, including the kidneys, and the fact that kidney damages are reported during severe cases of SARS-CoV-2. These findings may help us understand the new functions and mechanisms of NPC1L1 and could contribute to the identification of new antiviral targets.

Comparison of Clinico-pathologic features and outcomes of ANCA negative and ANCA positive pauci immune crescentic glomerulonephritis: A single centre study.

Introduction: Pauci-immune crescentic glomerulonephritis (PICN) is an important cause of rapidly progressive renal failure. 10-40% of PICN cases have ANCA (antineutrophil cytoplasmic antibody) negative serology. The present study compared clinico-pathologic features, Brix's renal risk score, Berden's histopathological classes and differences in outcome between ANCAnegative vs ANCA positive PICN patients. Materials and Methods: Sixty-one patients of biopsy-proven PICN were studied. Biochemical findings and ANCA serology were recorded. Renal biopsy slides were reviewed along with direct immunofluorescence. Clinical and histological features were compared between ANCA negative and positive PICN using the Man Whitney U test and Chi-square test. Patients were compared for distribution in Berden's histological classes and Brix's renal risk categories. Patient and renal survival were compared using Kaplan-Meier survival analysis. Results: ANCA negative PICN patients were younger (44.9 ± 16.5 years vs 53.6 ± 15.1 years, P = 0.049). Nasal (0 vs 18%, P = 0.035) and pulmonary involvement (9% vs 38%, P = 0.014) were lower in ANCA negative group. Both ANCA groups had similar renal biochemical profiles, percentage normal glomeruli, 16.3 ± 18.2 vs 21.7 ± 20.4 and percentage glomeruli with crescents, 64.5 ± 28.1 vs 64.3 ± 27.1. Twenty-seven per cent of ANCA negative cases fell in the sclerotic class in Berden's classification vs just 2.5% in ANCA positive group (p = 0.037) without significant difference in Brix's renal risk categories (p = 0.329). Thirteen per cent of ANCA negative patients achieved complete remission on treatment compared to 33% in ANCA positive patients. Patient survival and overall probability of progressing to ESRD were similar in the two groups. Conclusion: ANCA negative PICN cases present at younger ages. Nasal and pulmonary involvement is uncommon in these patients. Patient survival and progression to ESRD are similar in both ANCA groups.

Plant Cell-Engineered Gold Nanoparticles Conjugated to Quercetin Inhibit SARS-CoV-2 and HSV-1 Entry.

Recent studies have revealed considerable promise in the antiviral properties of metal nanomaterials, specifically when biologically prepared. This study demonstrates for the first time the antiviral roles of the plant cell-engineered gold nanoparticles (pAuNPs) alone and when conjugated with quercetin (pAuNPsQ). We show here that the quercetin conjugated nanoparticles (pAuNPsQ) preferentially inhibit the cell entry of two medically important viruses-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and herpes simplex virus type-1 (HSV-1) using different mechanisms. Interestingly, in the case of SARS-CoV-2, the pre-treatment of target cells with pAuNPsQ inhibited the viral entry, but the pre-treatment of the virus with pAuNPsQ did not affect viral entry into the host cell. In contrast, pAuNPsQ demonstrated effective blocking capabilities against HSV-1 entry, either during the pre-treatment of target cells or by inducing virus neutralization. In addition, pAuNPsQ also significantly affected HSV-1 replication, evidenced by the plaque-counting assay. In this study, we also tested the chemically synthesized gold nanoparticles (cAuNPs) of identical size and shape and observed comparable effects. The versatility of plant cell-based nanomaterial fabrication and its modification with bioactive compounds opens a new frontier in therapeutics, specifically in designing novel antiviral formulations.

Recombinant VEGF-C (Cys156Ser) improves mesenteric lymphatic drainage and gut immune surveillance in experimental cirrhosis.

Background & Aims: Lymphatic vessels (LVs) are crucial for maintaining abdominal fluid homoeostasis and immunity. In cirrhosis, mesenteric LVs (mLVs) are dilated and dysfunctional. Given the established role of vascular endothelial growth factor-C (VEGF-C) in improving LVs, we hypothesised that VEGF-C treatment could ameliorate the functions of mLVs in cirrhosis. Methods: In this study, we developed a nanoformulation comprising LV-specific growth factor, recombinant human VEGF-C (Cys156Ser) protein (E-VEGF-C) and delivered it orally in different models of rat cirrhosis to target mLVs. Cirrhotic rats were given nanoformulation without VEGF-C served as vehicles. Drainage of mLVs was analysed using tracer dye. Portal and systemic physiological assessments and computed tomography were performed to measure portal pressures and ascites. Gene expression and permeability of primary mesenteric lymphatic endothelial cells (LyECs) was studied. Immune cells in mesenteric lymph nodes (MLNs) were quantified by flow cytometry. Endogenous and exogenous gut bacterial translocation to MLNs was examined. Results: In cirrhotic rats, mLVs were dilated and leaky with impaired drainage. Treatment with E-VEGF-C induced proliferation of mLVs, reduced their diameter, and improved functional drainage. Ascites and portal pressures were significantly reduced in E-VEGF-C rats compared with vehicle rats. In MLNs of E-VEGF-C animals, CD8+CD134+ T cells were increased, whereas CD25+ regulatory T cells were decreased. Both endogenous and exogenous bacterial translocation were limited to MLNs in E-VEGF-C rats with reduced levels of endotoxins in ascites and blood in comparison with those in vehicle rats. E-VEGF-C treatment upregulated the expression of vascular endothelial-cadherin in LyECs and functionally improved the permeability of these cells. Conclusions: E-VEGF-C treatment ameliorates mesenteric lymph drainage and portal pressure and strengthens cytotoxic T-cell immunity in MLNs in experimental cirrhosis. It may thus serve as a promising therapy to manage ascites and reduce pathogenic gut bacterial translocation in cirrhosis. Impact and Implications: A human recombinant pro-lymphangiogenic growth factor, VEGF-C, was encapsulated in nanolipocarriers (E-VEGF-C) and orally delivered in different models of rat liver cirrhosis to facilitate its gut lymphatic vessel uptake. E-VEGF-C administration significantly increased mesenteric lymphatic vessel proliferation and improved lymph drainage, attenuating abdominal ascites and portal pressures in the animal models. E-VEGF-C treatment limited bacterial translocation to MLNs only with reduced gut bacterial load and ascitic endotoxins. E-VEGF-C therapy thus holds the potential to manage ascites and portal pressure and reduce gut bacterial translocation in patients with cirrhosis.

Archaic connectivity between the sulfated heparan sulfate and the herpesviruses - An evolutionary potential for cross-species interactions.

The structural diversity of metazoic heparan sulfate (HS) composed of unique sulfated domains is remarkably preserved among various vertebrates and invertebrate species. Interestingly the sulfated moieties of HS have been known as the key determinants generating extraordinary ligand binding sites in the HS chain to regulate multiple biological functions and homeostasis. One such ligand for 3-O sulfation in the HS chain is a glycoprotein D (gD) from an ancient herpesvirus, herpes simplex virus (HSV). This interaction between gD and 3-O sulfated HS leads to virus-cell fusion to promote HSV entry. It is quite astonishing that HSV-1, which infects two-thirds of the world population, is also capable of causing severe diseases in primates and non-primates including primitive zebrafish. Supporting evidence that HSV may cross the species barrier comes from the fact that an enzymatic modification in HS encoded by 3-O sulfotransferase-3 (3-OST-3) from a vertebrate zoonotic species enhances HSV-1 infectivity. The latter phenomenon suggests the possible role of sulfated-HS as an entry receptor during reverse zoonosis, especially during an event when humans encounter domesticated animals in proximity. In this mini-review, we explore the possibility that structural diversity in HS may have played a substantial role in species-specific adaptability for herpesviruses in general including their potential role in promoting cross-species transmission.

Prevalence, risk, and outcomes of venous thromboembolic events in kidney transplant recipients: a nested case-control study.

INTRODUCTION: Thromboembolism is more common in kidney transplant recipients (KTRs) than in the general population. Studies evaluating arterial and venous thromboembolism (VTE) in KTRs are scarce and the magnitude and risk factors are mostly undefined. METHODS: A nested control study was conducted from January 1, 2007, to December 31, 2019. Adult KTRs who were detected to have VTE events during this period were included. The primary outcome was to assess the prevalence of VTE in this population. Secondary outcomes were the assessment of the time to occurrence of the thromboembolic events after transplantation and assessing the risk factors and patient survival. For each subject studied, 4 controls were matched from the data set. RESULTS: Amongst 2158 patients, 97 (4.5%) were found to have VTE. The median follow-up time was 3.9 years (6-156 months). A total of 101 VTE events were recorded. The most common site of VTE was the lower limb deep vein thrombosis in 79 patients (0.03%)).In multivariate Cox regression analysis, serum creatinine of more than 3 mg/dl [HR 1.30, 95% CI (1.03-1.38)] was independently associated with increased VTE risk. Patients who developed a VTE had higher mortality as compared to patients who did not develop VTE. No increased risk of graft failure was found in VTE patients. CONCLUSION: This study suggests that kidney transplantation surgery is a moderate risk factor for VTE, and VTE is associated with higher morbidity and mortality. However, prospective studies are needed to establish a definite role of VTE in outcomes in KTRs.

Heparin-Induced Thrombocytopenia in Hemodialysis Patients- The First Study from India.

Heparin-induced thrombocytopenia (HIT), a rare complication of heparin therapy, presents with thrombocytopenia. It leads to paradoxical thromboembolism and has high mortality if untreated. It is less recognized, especially in hemodialysis (HD) patients who are frequently exposed to heparin during dialysis because patients with renal failure may have many other causes of thrombocytopenia. We describe the clinical presentation, diagnosis, and treatment of five cases of confirmed HIT in hemodialysis (HD) patients at our center. The initial suspicion was made based on a high 4T score and positive gel card test followed by confirmation using the functional assay with heparin-induced platelet aggregation. These patients were treated according to the recent American Society of Hematology guidelines 2018 for HIT.

Nocardiosis in Renal Transplantation: Case Series from India.

Nocardiosis is a rare opportunistic infection seen in kidney transplant patients and is caused by aerobic actinomycete. Disease manifestations can vary from a localized infection to multisystem organ failure. In this retrospective case series, we present 16 cases of Nocardiosis. The median age of the patients was 44 years. The median time from transplant to nocardiosis was 21 months. Acute rejection episodes and CMV infection within 6 months of nocardiosis were found in 12.5% and 25%, respectively. The most common organ involvement was the lungs (75%), followed by the brain (12.5%). Only one patient showed cutaneous involvement (6.25%). Mean creatinine at presentation was 0.7 mg/dL (mean eGFR: 92 ± 27 mL/min/1.73 m2). Trimethoprim/sulfamethoxazole resistance was found in 25% of patients. Five patients (31.25%) succumbed to the infection. Nocardiosis has a very low incidence but a high rate of mortality.

Health Systems Preparedness for Infectious Disease Outbreaks: Relevance for Nephrology.

The coronavirus disease (COVID-19) crisis glaringly highlighted the critical need to develop resilient health care systems that are better prepared for epidemics. Millions of people died from COVID-19 itself, but almost three times as many died from health system disruptions. People living with kidney disease are highly vulnerable during outbreaks and pandemics and their needs must be included in preparedness planning. Health systems preparedness requires not only early identification and containment of outbreaks and maintenance of critical services during crises, but also bolstering population resilience and ensuring the safety of both health personnel and patients. Planning for surge capacity in an outbreak must include provision for both acute and chronic dialysis, and ensure access to medications for people with kidney diseases. Quality of care should not be compromised and must be monitored and improved where necessary. Technology, such as telemedicine, can support quality and continuity of care and minimize infection risks. Communication at all levels is crucial to ensure all stakeholders, including communities, have the necessary information to support cooperation and collaboration in effective outbreak responses. Research is important during and after pandemics to improve knowledge and build resilience at all levels, from outbreak detection to the development of therapeutics and optimizing equity in access to interventions. Only with adequate preparation and more resilient health systems can we hope, as a global community, to build on the harsh lessons learned during COVID-19, and improve the response to the next infectious disease outbreak, epidemic, or even pandemic.

Atypical HUS Triggered by COVID-19: A Case Report.

We hereby present a case of an atypical hemolytic uremic syndrome (aHUS) precipitated by coronavirus disease 2019 (COVID-19). A 26-year-old male was diagnosed with COVID-19 and acute kidney injury. His kidney biopsy was suggestive of thrombotic microangiopathy. Five sessions of plasmapheresis were done but were discontinued in view of nonrecovery of kidney function. He was then referred for a kidney transplant. On genetic analysis, he was found to have mutations in the complement system (CFHR1 and CFHR3), which suggested this was a case of aHUS precipitated by COVID-19. In view of the high risk of recurrence of the primary disease in live-related kidney donor transplantation, he was advised for simultaneous liver and kidney transplants.

A potent virucidal activity of functionalized TiO2 nanoparticles adsorbed with flavonoids against SARS-CoV-2.

The coronavirus SARS-CoV-2 has caused a pandemic with > 550 millions of cases and > 6 millions of deaths worldwide. Medical management of COVID-19 relies on supportive care as no specific targeted therapies are available yet. Given its devastating effects on the economy and mental health, it is imperative to develop novel antivirals. An ideal candidate will be an agent that blocks the early events of viral attachment and cell entry, thereby preventing viral infection and spread. This work reports functionalized titanium dioxide (TiO2)-based nanoparticles adsorbed with flavonoids that block SARS-CoV-2 entry and fusion. Using molecular docking analysis, two flavonoids were chosen for their specific binding to critical regions of the SARS-CoV-2 spike glycoprotein that interacts with the host cell angiotensin-converting enzyme-2 (ACE-2) receptor. These flavonoids were adsorbed onto TiO2 functionalized nanoparticles (FTNP). This new nanoparticulate compound was assayed in vitro against two different coronaviruses; HCoV 229E and SARS-CoV-2, in both cases a clear antiviral effect was observed. Furthermore, using a reporter-based cell culture model, a potent antiviral activity is demonstrated. The adsorption of flavonoids to functionalized TiO2 nanoparticles induces a ~ threefold increase of that activity. These studies also indicate that FTNP interferes with the SARS-CoV-2 spike, impairing the cell fusion mechanism. KEY POINTS/HIGHLIGHTS: • Unique TiO2 nanoparticles displaying flavonoid showed potent anti-SARS-CoV-2 activity. • The nanoparticles precisely targeting SARS-CoV-2 were quantitatively verified by cell infectivity in vitro. • Flavonoids on nanoparticles impair the interactions between the spike glycoprotein and ACE-2 receptor.

Significance of chlorine-dioxide-based oral rinses in preventing SARS-CoV-2 cell entry.

OBJECTIVE: This work aims to determine the efficacy of preprocedural oral rinsing with chlorine dioxide solutions to minimize the risk of coronavirus disease 2019 (COVID-19) transmission during high-risk dental procedures. METHODS: The antiviral activity of chlorine-dioxide-based oral rinse (OR) solutions was tested by pre-incubating with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus in a dosage-dependent manner before transducing to human embryonic kidney epithelial (HEK293T-ACE2) cells, which stably expresses ACE-2 receptor. Viral entry was determined by measuring luciferase activity using a luminescence microplate reader. In the cell-to-cell fusion assay, effector Chinese hamster ovary (CHO-K1) cells co-expressing spike glycoprotein of SARS-CoV-2 and T7 RNA polymerase were pre-incubated with the ORs before co-culturing with the target CHO-K1 cells co-expressing human ACE2 receptor and luciferase gene. The luciferase signal was quantified 24 h after mixing the cells. Surface expression of SARS-CoV-2 spike glycoprotein and ACE-2 receptor was confirmed using direct fluorescent imaging and quantitative cell-ELISA. Finally, dosage-dependent cytotoxic effects of ORs were evaluated at two different time points. RESULTS: A dosage-dependent antiviral effect of the ORs was observed against SARS-CoV-2 cell entry and spike glycoprotein mediated cell-to-cell fusion. This demonstrates that ORs can be useful as a preprocedural step to reduce viral infectivity. CONCLUSIONS: Chlorine-dioxide-based ORs have a potential benefit for reducing SARS-CoV-2 entry and spread.