Phenolic compounds have been related to multiple biological activities, and the antiviral effect of these compounds has been demonstrated in several viral models of public health concern. In this review, we show the antiviral role of phenolic compounds against dengue virus (DENV), the most widespread arbovirus globally that, after its re-emergence, has caused multiple epidemic outbreaks, especially in the last two years. Twenty phenolic compounds with anti-DENV activity are discussed, including the multiple mechanisms of action, such as those directed against viral particles or viral proteins, host proteins or pathways related to the productive replication viral cycle and the spread of the infection.

Currently, no specific licensed antiviral exists for treating the illness caused by dengue virus (DENV). Therefore, the search for compounds of natural origin with antiviral activity is an important area of research. In the present study, three compounds were isolated and identified from seeds of Tabernaemontana cymosa plants. The in vitro antiviral effect of those compounds and voacangine against different DENV strains was assessed using different experimental approaches: compounds added before the infection (Pre), at the same time with the virus (Trans), after the infection (Post) or compounds present in all moments of the experiment (Pre-Trans-Post, Combined treatment). In silico studies (docking and molecular dynamics) were also performed to explain the possible antiviral mechanisms. The identified compounds were three structural analogs of voacangine (voacangine-7-hydroxyindolenine, rupicoline and 3-oxo-voacangine). In the Pre-treatment, only voacangine-7-hydroxyindolenine and rupicoline inhibited the infection caused by the DENV-2/NG strain (16.4% and 29.6% infection, respectively). In the Trans-treatment approach, voacangine, voacangine-7-hydroxyindolenine and rupicoline inhibited the infection in both DENV-2/NG (11.2%, 80.4% and 75.7% infection, respectively) and DENV-2/16681 infection models (73.7%, 74.0% and 75.3% infection, respectively). The latter strain was also inhibited by 3-oxo-voacangine (82.8% infection). Moreover, voacangine (most effective virucidal agent) was also effective against one strain of DENV-1 (DENV-1/WestPac/74) and against the third strain of DENV-2 (DENV-2/S16803) (48.5% and 32.4% infection, respectively). Conversely, no inhibition was observed in the post-treatment approach. The last approach (combined) showed that voacangine, voacangine-7-hydroxyindolenine and rupicoline inhibited over 90% of infections (3.5%, 6.9% and 3.5% infection, respectively) of both strains (DENV-2/NG and DENV-2/16681). The free energy of binding obtained with an in silico approach was favorable for the E protein and compounds, which ranged between −5.1 and −6.3 kcal/mol. Finally, the complex formed between DENV-2 E protein and the best virucidal compound was stable for 50 ns. Our results show that the antiviral effect of indole alkaloids derived from T. cymose depends on the serotype and the virus strain.

Despite the serious public health problem represented by the diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses, there are still no specific licensed antivirals available for their treatment. Here, we examined the potential anti-arbovirus activity of ten di-halogenated compounds derived from L-tyrosine with modifications in amine and carboxyl groups. The activity of compounds on VERO cell line infection and the possible mechanism of action of the most promising compounds were evaluated. Finally, molecular docking between the compounds and viral and cellular proteins was evaluated in silico with Autodock Vina^®, and the molecular dynamic with Gromacs^®. Only two compounds (TDC-2M-ME and TDB-2M-ME) inhibited both ZIKV and CHIKV. Within the possible mechanism, in CHIKV, the two compounds decreased the number of genome copies and in the pre-treatment strategy the infectious viral particles. In the ZIKV model, only TDB-2M-ME inhibited the viral protein and demonstrate a virucidal effect. Moreover, in the U937 cell line infected with CHIKV, both compounds inhibited the viral protein and TDB-2M-ME inhibited the viral genome too. Finally, the in silico results showed a favorable binding energy between the compounds and the helicases of both viral models, the NSP3 of CHIKV and cellular proteins DDC and β2 adrenoreceptor.

Introduction: Currently, there are no effective medications for treating all the clinical conditions of patients with COVID-19. We aimed to evaluate the antiviral activity of compounds derived from L-tyrosine against the B.1 lineage of SARS-CoV-2 in vitro and in silico. Methodology: The cytotoxicities of 15 halogenated compounds derived from L-tyrosine were evaluated in Vero-E6 cells by the MTT assay. The antiviral activity of the compounds was evaluated using four strategies, and viral quantification was performed by a plaque assay and qRT-PCR. The toxicity of the compounds was evaluated by ADMET predictor software. The affinity of these compounds for viral or cellular proteins and the stability of their conformations were determined by docking and molecular dynamics, respectively. Results: TODC-3M, TODI-2M, and YODC-3M reduced the viral titer >40% and inhibited the replication of viral RNA without significant cytotoxicity. In silico analyses revealed that these compounds presented low toxicity and binding energies between −4.3 and −5.2 Kcal/mol for three viral proteins (spike, Mpro, and RdRp). TODC-3M and YODC-3M presented the most stable conformations with the evaluated proteins. Conclusions: The most promising compounds were TODC-3M, TODI-2M, and YODC-3M, which presented low in vitro and in silico toxicity, antiviral potential through different strategies, and favorable affinities for viral targets. Therefore, they are candidates for in vivo studies.

Aim: Although current human transmission of monkeypox virus (MPXV) remains low, therapeutic options are limited. Biflavonoids, known for their antiviral properties, were evaluated in vitro and in silico against MPXV. Procedures: Three biflavonoids; Morelloflavone (Mo), Volkensiflavone (Vo), and Fukugiside (Fu); isolated from Garcinia madruno, were tested at concentrations of 1.6, 3.1, 6.3, and 12.5 µM against an MPXV strain isolated in Medellín, Colombia (2022). Combined, pre-, co-, and post-infection treatment strategies were assessed in Vero-E6 cells at a multiplicity of infection (MOI) of 2. Cytotoxicity, plaque reduction assays, and molecular docking analyses were performed. Results and Discussion: None of the biflavonoids exhibited cytotoxicity at concentrations up to 100 µM. All reduced MPXV infection by >70.9% across all concentrations under combined treatment strategies. In individual strategies at 6.3 µM, Mo, Vo, and Fu inhibited viral attachment by 59.4%, 79.3%, and 77.8%, respectively. Vo and Fu reduced the infection at co-treatment by 93.7% and 95.1%, respectively. Mo and Fu inhibited infection at post-entry steps by 64.4% and 56.7%, respectively. Molecular docking analyses revealed strong binding affinities (<–7.7 kcal/mol) between all biflavonoids and the MPXV proteins Methyltransferase and Poxin. Mo showed the most favorable binding energy (–8.4 kcal/mol), while Fu formed up to 12 hydrogen bonds with two catalytic residues of Methyltransferase. These findings indicate that biflavonoids could inhibit MPXV via distinct mechanisms: Mo affects both attachment and post-entry steps, while Vo and Fu show a possible direct activity against this virus and reduce attachment. Further studies are needed to validate their effects and clarify their therapeutic potential.

Introduction. Monkeypox cases have persisted in Colombia since the 2022 outbreak.Objective. To report the isolation and characterization of a monkeypox virus (MPXV) strain obtained from a Colombian patient during the 2022 outbreak, and to evaluate the antiviral potential of repurposed drugs against this isolate.Materials and methods. Lesion samples were inoculated into Vero-E6 cells. Viral isolation was characterized using virologic and molecular techniques. In addition, indirect immunofluorescence and neutralization assays were performed using convalescent serum. The antiviral activity of heparin, chloroquine, and ciprofloxacin was evaluated using a combined treatment strategy (multiplicity of infection = 2). Results. Cytopathic effect was observed 48 h post-infection. Viral titers reached 1.50 × 10⁶ PFU/ml. Phylogenetic analysis placed the isolate within clade IIb (B.1 lineage). Convalescent serum remained IFI-positive up to 1:160, and a 50% plaque reduction neutralization test of 35.6 was obtained. Chloroquine (50% inhibitory concentration ≈ 51.1 μM; selectivity index ≈ 2.2), heparin (50% inhibitory concentration ≈ 45.6 μg/ml; selectivity index ≈ 2.4), ciprofloxacin (50% inhibitory concentration ≈ 48.9 μM; selectivity index ≈ 3.9), and rifampicin (positive control; 50% inhibitory concentration ≈ 14.3 μM; selectivity index ≈ 19.7) significantly reduced MPXV infection. Molecular docking showed favorable binding of ciprofloxacin (-7.0 kcal/mol) and rifampicin (-7.2 kcal/mol) to the viral polymerase.Discussion. We successfully isolated and characterized an MPXV strain from a Colombian patient, establishing a platform for humoral and antiviral testing. Chloroquine, heparin, and ciprofloxacin showed measurable in vitro activity, supporting their potential for repurposing against this disease.