Explorations on the antiviral potential of zinc and magnesium salts against chikungunya virus: implications for therapeutics.

Background: Chikungunya virus (CHIKV), which causes chikungunya fever, is an arbovirus of public health concern with no approved antiviral therapies. A significant proportion of patients develop chronic arthritis after an infection. Zinc and magnesium salts help the immune system respond effectively against viral infections. This study explored the antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV infection. Methods: The highest non-toxic concentration of the salts (100 µM) was used to assess the prophylactic, virucidal, and therapeutic anti-CHIKV activities. Dose-dependent antiviral effects were investigated to find out the 50% inhibitory concentration of the salts. Entry bypass assay was conducted to find out whether the salts affect virus entry or post entry stages. Virus output in all these experiments was estimated using a focus-forming unit assay, real-time RT-PCR, and immunofluorescence assay. Results: Different time- and temperature-dependent assays revealed the therapeutic antiviral activity of zinc and magnesium salts against CHIKV. A minimum exposure of 4 hours and treatment initiation within 1 to 2 hours of infection are required for inhibition of CHIKV. Entry assays revealed that zinc salt affected virus-entry. Entry bypass assays suggested that both salts affected post-entry stages of CHIKV. In infected C57BL6 mice orally fed with zinc and magnesium salts, a reduction in viral RNA copy number was observed. Conclusion: The study results suggest zinc salts exert anti-CHIKV activity at entry and post entry stages of the virus life cycle, while magnesium salt affect CHIKV at post entry stages. Overall, the study highlights the significant antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV, which can be exploited in designing potential therapeutic strategies for early treatment of chikungunya patients, thereby reducing the virus-associated persistent arthritis.

Arctigenin from Arctium lappa L. inhibits chikungunya virus by affecting its entry and replication.

BACKGROUND: Dengue and chikungunya, caused by dengue virus (DENV) and chikungunya virus (CHIKV) respectively, are the most common arthropod-borne viral diseases worldwide, for which there are no FDA-approved antivirals or effective vaccines. Arctigenin, a phenylpropanoid lignan from the seeds of Arctium lappa L. is known for its anti-inflammatory, anti-cancer, antibacterial, and immunomodulatory properties. Arctigenin's antimicrobial and immunomodulatory capabilities make it a promising candidate for investigating its potential as an anti-DENV and anti-CHIKV agent. PURPOSE: The aim of the study was to explore the anti-DENV and anti-CHIKV effects of arctigenin and identify the possible mechanisms of action. METHODS: The anti-DENV or anti-CHIKV effects of arctigenin was assessed using various in vitro and in silico approaches. Vero CCL-81 cells were infected with DENV or CHIKV and treated with arctigenin at different concentrations, temperature, and time points to ascertain the effect of the compound on virus entry or replication. In silico molecular docking was performed to identify the interactions of the compound with viral proteins. RESULTS: Arctigenin had no effects on DENV. Various time- and temperature-dependent assays revealed that arctigenin significantly reduced CHIKV RNA copy number and infectious virus particles and affected viral entry. Entry bypass assay revealed that arctigenin inhibited the initial steps of viral replication. In silico docking results revealed the high binding affinity of the compound with the E1 protein and the nsp3 macrodomain of CHIKV. CONCLUSION: This study demonstrates the in-vitro anti-CHIKV potential of arctigenin and suggests that the compound might affect CHIKV entry and replication. Further preclinical and clinical studies are needed to identify its safety and efficacy as an anti-CHIKV drug.

Synthesis of novel rhodamine type Anthrone Spiro-lactam (ASL) analogues and evaluation of antiviral activity against dengue and chikungunya viruses.

A series of Rhodamine type Anthrone-Spirolactam (ASL) derivatives Benzylimin-Anthrone-Spirolactam (ASL-1 to ASL-10) and Benzamide-Anthrone-Spirolactam (ASL-11 and ASL-12) were synthesized via a simple condensation reaction between Anthrone Spiro-lactamine (2) and various aromatic aldehyde and acyl chlorides respectively. Since rhodamine-based compounds were reported to have antiviral activity, the ASL derivatives were examined for in vitro antiviral activity against dengue and chikungunya viruses. Among all the analogues, ASL-3, ASL-6, ASL-7, ASL-8, ASL-9 and ASL-10 were the most potent against dengue virus (DENV) and exerted around one log reduction in virus titre under post-treatment conditions. At the same time ASL-3 was effective under co-treatment conditions. Two analogues ASL-6 and ASL-12 exerted anti-chikungunya virus (CHIKV) activity under post-treatment conditions. In silico docking studies revealed that the ASL derivatives interacted with the proteins of DENV and CHIKV. Together, the results suggest the anti-DENV and CHIKV activity of ASL derivatives which may be exploited further for therapeutic purposes.

Serum ferritin level as a prognostic biomarker for predicting dengue disease severity: A systematic review and meta-analysis.

Serum ferritin levels serves as biomarkers in many inflammatory and infectious diseases. This current systematic review and meta-analysis evaluated whether serum ferritin levels are associated with severe dengue and its utility as a biomarker of disease severity. Literature searches were conducted in PubMed, Scopus, ScienceDirect, the Cochrane library, and Google Scholar. A total of 18 studies examining the serum ferritin levels in dengue cases in the context of disease severity (nine studies having dengue classification as non-severe vs. severe dengue cases, and nine studies having dengue classification as dengue without warning signs (DwoWS), dengue with warning signs (DwWS), and severe dengue cases) were included and the quality of the studies was assessed using the Quality in Prognostic Factor Studies tool. The meta-analysis was performed using STATA software to calculate the effect size as a standardized mean difference (SMD) or Hedges 'g' for the continuous outcome. Higher serum ferritin levels were found in severe dengue cases compared to non-severe cases [SMD (Hedges 'g') 4.05 (95% C.I. 2.09-6.00), (I2  = 98.8%)]. In the second group, DwWS cases showed high serum ferritin levels compared to DwoWS [SMD 2.01 (95% C.I. 0.92-3.10), (I2  = 97.89%)], and severe dengue cases showed higher levels of serum ferritin compared to DwWS [SMD 2.66 (95% C.I. 1.72-4.48), (I2  = 98.78%)] and DwoWS cases [SMD 6.65 (95% C.I. 1.72-11.59), (I2  = 99.78%]. Subgroup analysis for the country of study (India vs. others), ferritin testing methods, and ferritin measurement day revealed testing method as a significant contributor to heterogeneity. To conclude, the present study suggests serum ferritin as a prognostic marker for dengue disease severity. Multi-centric studies involving a large number of dengue patients with a uniform case definition accounting for all the confounding variables might help in determining a universal cut-off value to discriminate between non-severe and severe dengue.