Future Virology

Aim: 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. Materials & methods: 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...

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...

Aim: 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 & methods/materials: 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. Results: The C statistic was 83% (95% CI: 78%-87%) and the calibration plot showed that the model was well-calibrated...

Aim: This phase III study assessed the efficacy/safety/antiviral activity/pharmacokinetics of bemnifosbuvir, a novel, oral nucleotide analog to treat COVID-19. Patients & methods: 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. Results: 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...

Aim: Virtual screening of deep-sea fungal metabolites against SARS-CoV-2 Delta and Omicron spikes as potential antivirals. Materials & methods: Deep-sea fungal alkaloids (n ≥ 150) were evaluated against SARS-CoV-2, Delta and Omicron spikes, using various in silico approaches, including Admet scores, physiochemical properties, molecular docking (MD) and MD simulation (150 ns). Results: The test alkaloids complied with Admet scores and physiochemical properties within acceptable ranges, and followed Lipinski's rule of five...

AIM: This work aimed to investigate the antiviral activity of two 1,4-disubstituted-1,2,3-triazole derivatives ( 1 and 2 ) 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...

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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 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...

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. Ca2+ 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 Ca2+ level. On the other hand, viroporins have emerged as attractive targets for antiviral therapy due to their essential role in viral replication and pathogenesis...

AIM: The present study aimed to determine a correlation between differential TRIM56 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 TRIM56 gene expression were determined using a qPCR. RESULTS: TRIM56 gene showed significantly lower mRNA expression in the severe and mild groups compared with healthy individuals...

BACKGROUND: Bemnifosbuvir, a novel, oral, nonmutagenic, nonteratogenic nucleotide analogue inhibits SARS-CoV-2 replication in vitro . 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...

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...

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...

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...

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...

Aim: Rapid detection is crucial in complementing vaccination to reduce transmission of SARS-CoV-2. Materials & methods: Nasopharyngeal swabs (n = 213) and oropharyngeal swabs (n = 98) were tested. with the antigen rapid test kit. Results: Overall sensitivity (97.96%), specificity (100.00%) and coincidence rate (98.71%) were high, which translated into a positive predictive value of 100.00% and a negative predictive value of 96.64%. Conclusion: Antigen rapid tests have a great potential for screening in different settings to deliver results with high sensitivity and specificity...

Diabetic patients are at particular risk of severe COVID-19. Human dipeptidyl peptidase-4 (DPP-4) is a membrane-bound aminopeptidase that regulates insulin release by inactivating incretin. DPP-4 inhibitors (DPP-4is) are therefore used as oral anti-diabetic drugs to restore normal insulin levels. These molecules also have anti-inflammatory and anti-hypertension effects. Recent studies on the interactions of SARS-CoV-2 spike glycoprotein and DPP-4 predict a possible entry route for SARS-CoV-2. Therefore, DPP-4is could be effective at reducing the virus-induced 'cytokine storm', thereby ceasing inflammatory injury to vital organs...

Aim: This study aimed to analyze the phylogenetic relationships between the ACE2 of humans and other animals and investigate the potential interaction between SARS-CoV-2 RBD and ACE2 of different species. Materials & methods: The phylogenetic construction and molecular interactions were assessed using computational models. Results & conclusion: Despite the evolutionary distance, 11 species had a perfect fit for the interaction between their ACE2 and SARS-CoV-2 RBD ( Chinchilla lanigera, Neovison vison , Rhinolophus sinicus, Emballonura alecto , Saccopteryx bilineata , Numida meleagris )...

Aim: Bioinformatic analysis of mutation sets in receptor-binding domain (RBD) of currently and previously circulating SARS-CoV-2 variants of concern (VOCs) and interest (VOIs) to assess their ability to bind the ACE2 receptor. Methods: In silico sequence and structure-oriented approaches were used to evaluate the impact of single and multiple mutations. Results: Mutations detected in VOCs and VOIs led to the reduction of binding free energy of the RBD-ACE2 complex, forming additional chemical bonds with ACE2, and to an increase of RBD-ACE2 complex stability...

A fundamental basis for effective health-related policymaking of any democratic nation should be open and transparent communication between a government and its citizens, including scientists and healthcare professionals, to foster a climate of trust, especially during the ongoing COVID-19 mass vaccination campaign. Since misinformation is a leading cause of vaccine hesitancy, open data sharing through an evidence-based approach may render the communication of health strategies developed by policymakers with the public more effective, allowing misinformation and claims that are not backed by scientific evidence to be tackled...