Rabies is almost universally fatal if not treated before symptoms appear. Fortunately, post-exposure prophylaxis (PEP) is a nearly 100% effective treatment when started soon after rabies exposure. Nevertheless, rabies ca...Rabies is almost universally fatal if not treated before symptoms appear. Fortunately, post-exposure prophylaxis (PEP) is a nearly 100% effective treatment when started soon after rabies exposure. Nevertheless, rabies causes approximately 59,000 deaths annually, predominantly in rural parts of low- and middle-income countries. Current World Health Organization rabies PEP protocols require 1) a single administration of rabies immunoglobulin and 2) three or four doses of a vaccine administered over one to two weeks. The need for multiple healthcare visits significantly reduces treatment adherence due to financial, geographic, and other logistical barriers. Single-dose vaccine strategies represent a potential avenue to overcome these limitations by consolidating the vaccine dosing regimen into a single clinical interaction with a healthcare professional. This narrative review highlights several of the most promising technologies being used to pursue this goal, including mRNA vaccines, controlled-release formulations, and microneedle delivery systems. Although these strategies have yet to achieve clinical success in humans, data generated in preclinical studies and clinical trials offer insight into the limitations and potential benefits of these approaches as the field continues to seek a single-dose vaccine for PEP treatment. Highlighted articles were found by searching PubMed and Google Scholar, and published between January 2015 and August 2025.
Future Virol
· 2025 Aug · PMID 41112694
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(rat HEV) has become a zoonotic pathogen of growing public health concern. First identified in 2010 in wild rats in Germany, -C1 (HEV-C1) was genetically distinct from genotypes that cause hepatitis E in humans. Althoug...(rat HEV) has become a zoonotic pathogen of growing public health concern. First identified in 2010 in wild rats in Germany, -C1 (HEV-C1) was genetically distinct from genotypes that cause hepatitis E in humans. Although early research indicated that HEV-C1 could not infect non-human primates, reports of human infections in Hong Kong circa 2018 raised the possibility of a new zoonoses. Currently, 23 known human instances of rat HEV infection have been reported, affecting both immunocompetent and immunocompromised individuals. A critical review of the current knowledge regarding rat HEV, including its epidemiology, zoonotic spillover, health implications, and knowledge gaps with future research directions is presented in this paper. Here we describe possible modes of transmission, human pathophysiology, and clinical signs and symptoms in infected people. The need for diagnostic tools specific for rat HEV, current detection limitations, and diagnostic challenges are also discussed. We explore potential implications for public health, stressing the value of rodent control, surveillance, and preventive measures. Knowledge gaps in the field of rat HEV research are highlighted and future lines of inquiry to reduce the potential risks to public health posed by this emerging zoonotic virus are discussed.
Future Virol
· 2025 Jul · PMID 40963815
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Polyomaviruses (PyVs) are widespread commensals among vertebrates, including humans, where they silently persist lifelong in healthy hosts. Polyomavirus infection in immunocompromised individuals can cause life-threateni...Polyomaviruses (PyVs) are widespread commensals among vertebrates, including humans, where they silently persist lifelong in healthy hosts. Polyomavirus infection in immunocompromised individuals can cause life-threatening diseases. Of the 14 human polyomaviruses discovered to date, resurgent infections by the JC and BK PyVs are responsible for high morbidity and mortality in individuals with certain inherited or acquired immune perturbations. JCPyV causes several brain disorders, the most fully characterized and of highest (albeit rare) incidence being Progressive Multifocal Leukoencephalopathy (PML). BKPyV infection elicits a diffuse interstitial nephritis in up to 10% of allograft kidneys, and approximately 10% of allogeneic hematopoietic stem cell transplant recipients develop BKPyV-associated hemorrhagic cystitis. No clinically efficacious anti-PyV agents are available. Because PyVs are species-specific, determinants of pathogenesis by human PyVs are inferred from infection of cells in tissue culture. Insights into viral and immunological factors that enable PyVs to persist and cause central nervous system (CNS) and kidney disease in vivo have emerged from recent studies using mouse PyV (MuPyV), a natural murine pathogen. In this perspective, we discuss recent findings using the MuPyV-mouse model to understand early immunovirologic events of CNS and kidney infection, the development of PyV antiviral agents, and promising research directions for polyomavirology.
The cells infected by a virus are critical determinants of infection and disease. These same susceptible cells can also provide a wide range of options for viral propagation. The type of cell used to produce a virus, i....The cells infected by a virus are critical determinants of infection and disease. These same susceptible cells can also provide a wide range of options for viral propagation. The type of cell used to produce a virus, i.e. the producer cell type, can change the macromolecular composition of viruses and other factors associated with viral inoculum independent of genetic selection. Changes in the post-translational modifications of viral proteins, virion protein and lipid composition, and the types of viral structures released from different producer cells have been observed for several virus families. These producer cell-dependent changes can have wide ranging consequences on subsequent infection by altering viral tropism, antigenicity, and overall infectious capacity. The changes imparted by the producer cell impact experimental outcomes and influence viral spread and disease . In this review, we discuss the literature documenting the effects that producer cell type has on the macromolecular composition and infectious properties of virions and viral inoculum. We discuss the evidence of producer cell-dependent changes on the outcome of infection and antigenicity from diverse viral families. These observations highlight the need to better understand the impact producer cell type has on viral infections and disease.
Subramanian S, Schnell G, Iulio JD
… +8 more, Gupta AK, Shapiro AE, Sarkis EH, Lopuski A, Peppercorn A, Aldinger M, Hebner CM, Cathcart AL
Future Virol
· 2023 Nov · PMID 38074312
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Sotrovimab is an engineered human monoclonal antibody that binds a conserved region of the SARS-CoV-2 spike protein. The COMET-ICE phase III study evaluated sotrovimab for treatment of mild to moderate COVID-19 in nonhos...Sotrovimab is an engineered human monoclonal antibody that binds a conserved region of the SARS-CoV-2 spike protein. The COMET-ICE phase III study evaluated sotrovimab for treatment of mild to moderate COVID-19 in nonhospitalized participants with ≥1 risk factor for severe disease progression. We evaluated the presence of circulating SARS-CoV-2 variants of concern or interest (VOCs/VOIs) and characterized the presence of baseline, post-baseline and emergent amino acid substitutions detected in the epitope of sotrovimab in SARS-CoV-2. None of the sotrovimab-treated participants with baseline epitope substitutions, and 1 of 48 sotrovimab-treated participants with post-baseline epitope substitutions, met the primary clinical endpoint for progression. Overall, progression was not associated with identified VOC/VOI or the presence of epitope substitutions in sotrovimab-treated participants.
Abdelrady YA, Ashraf NM, Hamid A
… +5 more, Thabet HS, Sayed AM, Salem SH, Hassanein EH, Sayed AM
Future Virol
· 2023 Apr · PMID 38052000
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AIM: We aimed to investigate the potential inhibitory effects of diterpenes on SARS-CoV-2 main protease (Mpro). MATERIALS & METHODS: We performed a virtual screening of diterpenoids against Mpro using molecular docking,...AIM: We aimed to investigate the potential inhibitory effects of diterpenes on SARS-CoV-2 main protease (Mpro). MATERIALS & METHODS: We performed a virtual screening of diterpenoids against Mpro using molecular docking, molecular dynamics simulation and absorption, distribution, metabolism and excretion) analysis. RESULTS: Some tested compounds followed Lipinski's rule and showed drug-like properties. Some diterpenoids possessed remarkable binding affinities with SARS-CoV-2 Mpro and drug-like pharmacokinetic properties. Three derivatives exhibited structural deviations lower than 1 Å. CONCLUSION: The findings of the study suggest that some of the diterpenes could be candidates as potential inhibitors for Mpro of SARS-CoV-2.
Tavakoli R, Rahimi P, Hamidi-Fard M
… +6 more, Eybpoosh S, Doroud D, Ahmadi I, Anvari E, Aghasadeghi M, Fateh A
Future Virol
· 2023 Jun · PMID 38051999
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AIM: The present study aimed to determine a correlation between differential expression levels and severe infections of COVID-19 between the Alpha, Delta and Omicron BA.5 variants. MATERIALS & METHODS: This study was pe...AIM: The present study aimed to determine a correlation between differential expression levels and severe infections of COVID-19 between the Alpha, Delta and Omicron BA.5 variants. MATERIALS & METHODS: This study was performed on 330 COVID-19 patients, including 142 with severe and 188 with mild infections, as well as 160 healthy controls. The levels of gene expression were determined using a qPCR. RESULTS: gene showed significantly lower mRNA expression in the severe and mild groups compared with healthy individuals. Our finding indicated the high and low reduction of mRNA expression in Delta and Omicron BA.5 variant, respectively. CONCLUSION: Further research is needed to characterize the impact of TRIM proteins on the severity of COVID-19.
Liu J, Cang T, Jiang C
… +7 more, Li K, Liu S, Wang H, Wang M, Chen Y, Shao Y, Liu J
Future Virol
· 2023 May · PMID 38051998
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AIM: This study used CpG 684 as adjuvant of inactivated COVID-19 vaccine to detect a humoral and cellular immune response in mice. MATERIALS & METHODS: We used 10 and 20 µg CpG 684 as adjuvants of an inactivated COVID-19...AIM: This study used CpG 684 as adjuvant of inactivated COVID-19 vaccine to detect a humoral and cellular immune response in mice. MATERIALS & METHODS: We used 10 and 20 µg CpG 684 as adjuvants of an inactivated COVID-19 vaccine to immunize mice. IgG, IgG1, IgG2a, IgG2b and IgM binding antibodies were detected in serum by ELISA. The IFN-γ cytokine was detected by ELISPOT. RESULTS: CpG 684 improved spike-specific IgG and IgM subtype binding antibodies and increased the neutralizing antibody titer against prototype, Delta and Beta strains. CpG 684 also improved cellular immune response. CONCLUSION: CpG 684 is an effective adjuvant for inactivated COVID-19 vaccine.
Horga A, Kuritzkes DR, Kowalczyk JJ
… +5 more, Pietropaolo K, Belanger B, Lin K, Perkins K, Hammond J
Future Virol
· 2023 Jun · PMID 38051993
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BACKGROUND: Bemnifosbuvir, a novel, oral, nonmutagenic, nonteratogenic nucleotide analogue inhibits SARS-CoV-2 replication . MATERIALS & METHODS: Adults in hospital settings with moderate COVID-19 were randomized 1:1 bem...BACKGROUND: Bemnifosbuvir, a novel, oral, nonmutagenic, nonteratogenic nucleotide analogue inhibits SARS-CoV-2 replication . MATERIALS & METHODS: Adults in hospital settings with moderate COVID-19 were randomized 1:1 bemnifosbuvir/placebo. Study amended to two parts after interim analysis; part B enrollment limited owing to evolving standard of care. RESULTS: Although the study ended early and did not meet the primary efficacy end point, bemnifosbuvir was well tolerated and did not contribute to all-cause mortality. Compared with placebo, bemnifosbuvir treatment resulted in 0.61 log greater viral load mean change on day 2; trend sustained through day 8. Treatment-emergent adverse events were similar in both groups; most were mild/moderate, unrelated to study drug. CONCLUSION: Our results suggest a potential role for bemnifosbuvir in blunting COVID-19 progression. CLINICAL TRIAL REGISTRATION: NCT04396106 (ClinicalTrials.gov).
Nguyen CM, Luong BA, Thi Tran TT
… +2 more, Nguyen HN, Tran LS
Future Virol
· 2023 Jun · PMID 38051989
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AIM: To generate mRNAs encoding conserved regions within SARS-CoV-2 ORF1ab which can induce strong T-cell responses to overcome the immune invasion of newly emergent variants. METHODS: We selected two conserved regions w...AIM: To generate mRNAs encoding conserved regions within SARS-CoV-2 ORF1ab which can induce strong T-cell responses to overcome the immune invasion of newly emergent variants. METHODS: We selected two conserved regions with a high density of T-cell epitopes using immunoinformatics for mRNA synthesis. The ability of testing mRNAs to activate T cells for IFN-γ production was examined by an ELISpot assay and flow cytometry. RESULTS: Two synthesized mRNAs were successfully translated in MDA-MB-231 cells and had comparable potency to the spike mRNA to induce CD4 and CD8 T-cell responses in peripheral blood mononuclear cells in 29 out of 34 participants. CONCLUSION: This study provides a proof-of-concept for the use of SARS-CoV-2 conserved regions to develop booster vaccines capable of eliciting T-cell-mediated immunity.
Future Virol
· 2023 May · PMID 38051986
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AIM: Structure-based identification of natural compounds against SARS-CoV-2, Delta and Omicron target proteins. MATERIALS & METHODS: Several known antiviral natural compounds were subjected to molecular docking and MD si...AIM: Structure-based identification of natural compounds against SARS-CoV-2, Delta and Omicron target proteins. MATERIALS & METHODS: Several known antiviral natural compounds were subjected to molecular docking and MD simulation against SARS-CoV-2 Mpro, Helicase and Spike, including Delta and Omicron Spikes. RESULTS: Of the docked ligands, 20 selected for each complex exhibited overall good binding affinities (-7.79 to -5.06 kcal/mol) with acceptable physiochemistry following Lipinski's rule. Finally, two best ligands from each complex upon simulation showed structural stability and compactness. CONCLUSION: Quercetin-3-acetyl-glucoside, Rutin, Kaempferol, Catechin, Orientin, Obetrioside and Neridienone A were identified as potential inhibitors of SARS-CoV-2 Mpro, Helicase and Spike, while Orientin and Obetrioside also showed good binding affinities with Omicron Spike. Catechin and Neridienone A formed stable complexes with Delta Spike.
Rabelo VW, da Silva VD, Sanchez Nuñez ML
… +5 more, Dos Santos Corrêa Amorim L, Buarque CD, Kuhn RJ, Abreu PA, Nunes de Palmer Paixão IC
Future Virol
· 2023 Sep · PMID 37974899
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AIM: This work aimed to investigate the antiviral activity of two 1,4-disubstituted-1,2,3-triazole derivatives ( and ) against Chikungunya virus (CHIKV) replication. MATERIALS & METHODS: Cytotoxicity was analyzed using c...AIM: This work aimed to investigate the antiviral activity of two 1,4-disubstituted-1,2,3-triazole derivatives ( and ) against Chikungunya virus (CHIKV) replication. MATERIALS & METHODS: Cytotoxicity was analyzed using colorimetric assays and the antiviral potential was evaluated using plaque assays and computational tools. RESULTS: Compound 2 showed antiviral activity against CHIKV 181-25 in BHK-21 and Vero cells. Also, this compound presented a higher activity against CHIKV BRA/RJ/18 in Vero cells, like compound 1. Compound 2 exhibited virucidal activity and inhibited virus entry while compound 1 inhibited virus release. Molecular docking suggested that these derivatives inhibit nsP1 protein while compound 1 may also target capsid protein. CONCLUSION: Both compounds exhibit promising antiviral activity against CHIKV by blocking different steps of virus replication.
Future Virol
· 2023 Oct · PMID 37970095
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The unprecedented scale of the SARS-CoV-2 pandemic has driven considerable investigation into novel antiviral treatments since effective vaccination strategies cannot completely eradicate the virus. Apitherapy describes...The unprecedented scale of the SARS-CoV-2 pandemic has driven considerable investigation into novel antiviral treatments since effective vaccination strategies cannot completely eradicate the virus. Apitherapy describes the medicinal use of bee venom, which may be an effective treatment against SARS-CoV-2 infection. Bee venom contains chemicals that are antimicrobial and stimulate the immune system to counteract viral load. The present review focuses on the use of bee venom as a possible treatment for COVID-19 and reviews studies on the pharmacodynamics of bee venom.
Mohammedain SA, Badran S, Elzouki AY
… +10 more, Salim H, Chalaby A, Siddiqui M, Hussein YY, Rahim HA, Thalib L, Alam MF, Al-Badriyeh D, Al-Maadeed S, Doi SA
Future Virol
· 2023 Oct · PMID 37970094
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This study aims to perform an external validation of a recently developed prognostic model for early prediction of the risk of progression to severe COVID-19. Patients were recruited at their initial diagnosis at two fa...This study aims to perform an external validation of a recently developed prognostic model for early prediction of the risk of progression to severe COVID-19. Patients were recruited at their initial diagnosis at two facilities within Hamad Medical Corporation in Qatar. 356 adults were included for analysis. Predictors for progression of COVID-19 were all measured at disease onset and first contact with the health system. The C statistic was 83% (95% CI: 78%-87%) and the calibration plot showed that the model was well-calibrated. The published prognostic model for the progression of COVID-19 infection showed satisfactory discrimination and calibration and the model is easy to apply in clinical practice.d.
Horga A, Saenz R, Yilmaz G
… +13 more, Simón-Campos A, Pietropaolo K, Stubbings WJ, Collinson N, Ishak L, Zrinscak B, Belanger B, Granier C, Lin K, C Hurt A, Zhou XJ, Wildum S, Hammond J
Future Virol
· 2023 Oct · PMID 37928891
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This phase III study assessed the efficacy/safety/antiviral activity/pharmacokinetics of bemnifosbuvir, a novel, oral nucleotide analog to treat COVID-19. Outpatient adults/adolescents with mild-to-moderate COVID-19 wer...This phase III study assessed the efficacy/safety/antiviral activity/pharmacokinetics of bemnifosbuvir, a novel, oral nucleotide analog to treat COVID-19. Outpatient adults/adolescents with mild-to-moderate COVID-19 were randomized 2:1 to bemnifosbuvir/placebo. Time to symptom alleviation/improvement (primary outcome), risk of hospitalization/death, viral load and safety were evaluated. Although the study was discontinued prematurely and did not meet its primary end point, bemnifosbuvir treatment resulted in fewer hospitalizations (71% relative risk reduction), COVID-19-related medically attended hospital visits, and COVID-19-related complications compared with placebo. No reduction in viral load was observed. The proportion of patients with adverse events was similar; no deaths occurred. Bemnifosbuvir showed hospitalization reduction in patients with variable disease progression risk and was well tolerated. : NCT04889040 (ClinicalTrials.gov).
Future Virol
· 2023 Oct · PMID 37908844
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Virtual screening of deep-sea fungal metabolites against SARS-CoV-2 Delta and Omicron spikes as potential antivirals. Deep-sea fungal alkaloids (n ≥ 150) were evaluated against SARS-CoV-2, Delta and Omicron spikes, usin...Virtual screening of deep-sea fungal metabolites against SARS-CoV-2 Delta and Omicron spikes as potential antivirals. Deep-sea fungal alkaloids (n ≥ 150) were evaluated against SARS-CoV-2, Delta and Omicron spikes, using various approaches, including Admet scores, physiochemical properties, molecular docking (MD) and MD simulation (150 ns). The test alkaloids complied with Admet scores and physiochemical properties within acceptable ranges, and followed Lipinski's rule of five. Of these, -derived cladosin K (tetramate alkaloid) for SARS-CoV-2, -derived saphenol (phenazine alkaloid) for Delta and -derived chaetoglobosin E (quinoline alkaloid) for Omicron were identified as potential spike-inhibitors. Our data therefore, strongly warrants further experimental validations of cladosin K, saphenol and chaetoglobosin E, especially against the Omicron and Delta spikes.
Future Virol
· 2023 Aug · PMID 37822684
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Since 2020, the highly contagious nature and various transmission routes of SARS-CoV-2 have rendered the pandemic interminable. Vertical transmission (VT) through the placenta and breast milk, which is frequent for certa...Since 2020, the highly contagious nature and various transmission routes of SARS-CoV-2 have rendered the pandemic interminable. Vertical transmission (VT) through the placenta and breast milk, which is frequent for certain virus types, is thought to exist for SARS-CoV-2 and is hypothesized by many researchers. Conversely, antibodies are produced to counteract the effect of viruses. Since newborns' immunologic system cannot produce proper antibodies, maternal antibodies are usually transferred from mother to infant/fetus to meet the need. This theory leads to the hypothesis of transmission of antibodies through the placenta and breast milk following SARS-CoV-2 infection or vaccination. This paper further discusses these hypotheses, considering consequences of fetus/infant harm versus benefit.
Fani M, Moossavi M, Bakhshi H
… +4 more, Jahrodi AN, Khazdair MR, Zardast AH, Ghafari S
Future Virol
· 2023 Aug · PMID 37700758
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Despite passing the pandemic phase of the COVID-19, researchers are still investigating various drugs. Previous evidence suggests that blocking the calcium channels may be a suitable treatment option. Ca is required to e...Despite passing the pandemic phase of the COVID-19, researchers are still investigating various drugs. Previous evidence suggests that blocking the calcium channels may be a suitable treatment option. Ca is required to enhance the fusion process of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also, some important inflammatory factors during SARS-CoV-2 infection are dependent on Ca level. On the other hand, viroporins have emerged as attractive targets for antiviral therapy due to their essential role in viral replication and pathogenesis. By inhibiting the host calcium channels and viroporins, it is possible to limit the spread of infection. Therefore, calcium channel blockers (CCBs) and drugs targeting Viroporins can be considered an effective option in the fight against SARS-CoV-2.